Critical care outcomes of hemophagocytic lymphohistiocytosis in children: a single centre retrospective observational study

Critical care outcomes of hemophagocytic lymphohistiocytosis in children: a single centre retrospective observational study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Critical care outcomes of hemophagocytic lymphohistiocytosis in children: a single centre retrospective observational study Manuel Murciano, Gabriella Bottari, Denise Pires Marafon, Francesca De Luca, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8216536/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a challenging and potentially life-threatening condition characterized by an uncontrolled inflammatory response resulting from hyperactivation of T lymphocytes and macrophages, leading to excessive production of inflammatory cytokines. HLH can lead to multiple organ failure and death in a significant proportion of cases. It is challenging to differentiate HLH from sepsis. This study aims to describe the clinical characteristics, risk factors, and outcomes of a cohort of children admitted to a pediatric intensive care unit (PICU) with primary and secondary hemophagocytic lymphohistiocytosis (pHLH and sHLH). Methods: Retrospective observational analysis of all children with HLH admitted to the PICU between 2006 and 2019. Results: Patients were evaluated at two time points: upon PICU admission (T1) and at the time of the highest ferritin level (T2). A total of 48 patients were included: 5 with pHLH, 37 with sHLH, and 6 with macrophage activation syndrome (MAS) in the context of systemic juvenile idiopathic arthritis (sJIA). The overall mortality rate in the PICU was 33.3%. Mortality rates within each group were: 60% for pHLH, 35.1% for sHLH, and nobody for MAS. The Pediatric Index of Mortality (PIM2) was higher among non-survivors. Splenomegaly and leukopenia at PICU admission were more common in non-survivors compared to survivors, as were the incidence of multiple organ failure and acute renal failure during the PICU stay. Platelet counts were significantly lower in patients who died, but only at T2. Ferritin levels remained consistently elevated in non-survivors throughout their PICU stay. Conclusions: In this cohort, mortality among children admitted to the PICU with HLH was high, particularly among those with primary or onco-hematological forms. Conversely, patients with MAS experienced more relapses but no mortality was observed in this sample. Early presence of splenomegaly, low platelet count, elevated ferritin levels, and PIM2 score at PICU admission appear to be indicators of poor prognosis. These findings may help to early identify patients at highest risk for complications and mortality. hemophagocytic lymphohistiocytosis HLH macrophage activation syndrome MAS pediatric intensive care PICU extracorporeal support organ failure mortality inflammation BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a challenging and potentially life-threatening condition characterized by an uncontrolled inflammatory response resulting from hyperactivation of T lymphocytes and macrophages, leading to excessive production of inflammatory cytokines. The main clinical features include fever, lymphadenopathy, hepatosplenomegaly, coagulopathy, and dysfunction of the renal, hepatic, and central nervous systems. Refractory HLH to medical therapy may progress to multiple organ failure (MOF) and death in a significant proportion of cases [ 1 ]. Typical laboratory findings encompass cytopenia affecting one or more cell lines (anemia, leukopenia, and thrombocytopenia), elevated transaminases, lactate dehydrogenase (LDH), ferritin, D-dimers, and decreased fibrinogen levels [ 2 ]. HLH can be classified as primary (pHLH), also known as familial HLH, or secondary (sHLH), also referred to as reactive HLH. pHLH results from genetic defects involved in the cytotoxic pathway, whereas sHLH can be triggered by various conditions such as infections, rheumatological diseases, and malignancies. However, in a notable percentage of cases, no specific trigger can be identified [ 3 ]. Infectious triggers are predominantly herpesviruses, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV), as well as influenza viruses (notably H1N1) and Leishmania. Rheumatological diseases are also common triggers of sHLH, particularly systemic juvenile idiopathic arthritis (sJIA), systemic lupus erythematosus (SLE), Kawasaki disease, and systemic vasculitis. These forms are often referred to as macrophage activation syndrome (MAS) [ 4 – 8 ]. Other predisposing conditions include malignancies (most frequently lymphoma and leukemia), immunological disorders, and metabolic diseases. In 15–40% of cases, no identifiable trigger for sHLH can be determined [ 9 ]. Severe forms of HLH may necessitate admission to the PICU and the use of advanced organ support [ 14 ]. In this context, accurate differential diagnosis from acute conditions such as sepsis—which requires entirely different treatment strategies—is essential to improve patient outcomes [ 15 ]. Therefore, the primary objective of this study is to describe the clinical characteristics, risk factors—including the need for extracorporeal therapies—laboratory parameters, and prognostic outcomes (such as duration of mechanical ventilation, length of PICU stay, and survival) of patients admitted to the PICU with HLH. Additionally, the study aims to identify early predictors of clinical outcomes. METHODS We conducted a retrospective review of all patients with primary and secondary HLH who required PICU admission from 2006 to 2019. The diagnosis of HLH was based on the HLH-2004 diagnostic guidelines and the MAS-2016 classification criteria [ 16 , 17 ]. The study received approval from the Institutional Review Board of Children Hospital Bambino Gesù. Informed consent was waived due to the retrospective nature of the study. Clinical features, laboratory parameters, and supportive therapies were extracted from electronic medical records. Patients were evaluated at two time points: at PICU admission (T1) and at the time of the highest ferritin level (T2) during their PICU stay. The risk of mortality was assessed using the Pediatric Index of Mortality (PIM2) score at PICU admission (T1). Organ dysfunction was evaluated using the hepato-biliary dysfunction and diffuse intravascular coagulation (DIC) scores [ 1 , 18 ]. The primary objective was to describe the clinical and laboratory parameters related to HLH, as well as prognostic outcomes, comparing survivors and non-survivors after PICU admission. Mortality was defined as death occurring during the PICU stay. We considered the following risk factors for mortality in our population: invasive mechanical ventilation (MV), extracorporeal organ support (including extracorporeal membrane oxygenation, ECMO), and extracorporeal blood purification techniques (such as Continuous Renal Replacement Therapy, CRRT; hemoadsorption; and plasma exchange). Additionally, we evaluated complications as potential risk factors for mortality, including disseminated intravascular coagulation, hepatobiliary dysfunction, and central nervous system involvement during PICU stay. Descriptive statistics were employed in this study. The distribution of the variables under investigation was assessed using the Shapiro-Wilk test, along with measures of skewness and kurtosis. Since the primary variables did not follow a Gaussian distribution, continuous data were summarized using medians and interquartile ranges (first and third quartiles) and compared with the Mann-Whitney U test. Categorical variables were expressed as absolute and percentage frequencies, with group comparisons performed using the Chi-square test or Fisher’s exact test, as appropriate. A p-value of less than 0.05 (two-tailed) was considered statistically significant. Data were stored in an Excel database, and all statistical analyses were conducted using Stata software version 15.1 (StataCorp, College Station, TX). RESULTS 48 patients were included in this study. Baseline clinical characteristics are summarized in Table 1 . The sample comprised 22 females (45.8%) and 26 males (54.2%). Table 1 Characteristics of the 48 patients stratified by diagnosis (pHLH, MAS in sJIA and sHLH by other triggers). pHLH sHLH p value Characteristics MAS in sJIA sHLH from other triggers pHLH vs sHLH MAS vs sHLH (N = 5) (N = 6) (N = 37) Gender, Females 1 2 (40,0) 4 (66,7) 16 (43,2) 1,0 0,39 Age at onset (years) 2 1,0 (0,6 − 1,8) 8,5 (1,8–12,3) 5,6 (1,2–11,6) 0,068 0,57 Age at PICU admission (years) 2 1,8 (1,2–3,7) 8,5 (1,8–13,3) 5,5 (2,6–11,5) 0,095 0,56 Trigger 1 - - Onco-Hematological - 0 (0,0) 2 (5,4) - - Infectious - 0 (0,0) 21 (56,8) - - Rheumatological - 6 (100) 8 (21,6) - - Undefined - 0 (0,0) 6 (16,2) - - MAS criteria 1 - 6 (100) - - - Criteria HLH-2004 1 5 (100) - 30 (81,1) 0,57 - 1 Number (%) –Fisher's exact test; 2 Median (1st-3rd quartile) - Mann-Whitney test. Patients with secondary hemophagocytic lymphohistiocytosis (sHLH) were stratified according to their predisposing conditions. In two patients (4.7%), the predisposing condition was a hematological disease—specifically, primary combined immunodeficiency and Hodgkin’s lymphoma. In 21 patients (48.8%), the predisposing factor was an infection, including one case of Leishmania, viral agents in 12 patients (Rhinovirus, H1N1, EBV, HHV6, VZV, Bocavirus), and bacterial etiology in 8 patients. Fourteen patients (32.6%) had a rheumatological disease as the predisposing factor, with specific diagnoses including five cases of systemic juvenile idiopathic arthritis (sJIA), two with NLRC4-gain of function, one with systemic lupus erythematosus (SLE), one with Kawasaki syndrome, one with an interferonopathy (spondyloenchondrodysplasia, SPENCD), one with Rasmussen syndrome, one with antiphospholipid antibody syndrome, and one with ANCA-positive vasculitis. In 56.8% of cases, HLH was triggered by an infectious event (e.g., EBV, CMV, H1N1, sepsis). The different forms of HLH showed varying ages at disease onset: primary HLH (pHLH) at approximately 1 year, macrophage activation syndrome (MAS) in sJIA at around 8.5 years, and sHLH at about 5.6 years. All patients with pHLH presented with fever, splenomegaly, and hemophagocytosis observed in bone marrow aspirates. Conversely, in sHLH, fever was the most common clinical symptom (94.6%), followed by splenomegaly in 56.8% of cases and in 33.3% of MAS cases. Hemophagocytosis in bone marrow was observed in 76% of sHLH cases and 60% of MAS cases (see Table 2 ). Table 2 Description of symptoms and organ damage of the 48 patients stratified by diagnosis (pHLH, MAS in sJIA and sHLH by other triggers). pHLH sHLH p value Symptoms and organ damage MAS in sJIA sHLH from other triggers pHLH vs sHLH MAS vs sHLH (N = 5) (N = 6) (N = 37) Fever 5 (100) 5 (83,3) 35 (94,6) 1,0 0,37 Splenomegaly 5 (100) 2 (33,3) 21 (56,8) 0,14 0,39 Hemophagocytosis (Bone marrow aspirate or biopsy) 4/4 (100) 3/5 (60,0) 19/25 (76,0) 0,55 0,64 Central Nervous System involvement 2 (40,0) 2 (33,3) 24 (64,9) 0,35 0,19 Multi-organ failure 2 (40,0) 1 (16,7) 14 (37,8) 1,0 0,40 Acute kidney injury 2 (40,0) 1 (16,7) 17 (46,0) 1,0 0,38 HBD at PICU admission 0 (0,0) 3 (50,0) 19 (51,4) 0,053 1,0 HBD at T2 2 (40,0) 1 (16,7) 26 (70,3) 0,31 0,021 Legend: HBD = hepato-biliary dysfunction. Relapse of disease, defined as a new HLH episode during PICU stay, occurred in 20% of pHLH patients, 66.7% of MAS patients with sJIA, and 18.9% of sHLH patients from other predisposing conditions. The difference between MAS and sHLH relapse rates was statistically significant (p = 0.029; see Table 3 ). Table 3 also details the Pediatric Index of Mortality 2 (PIM2) scores at T1, length of PICU stay, and mortality rates. Table 3 Outcomes of the 48 patients stratified by diagnosis (pHLH, MAS in sJIA and sHLH by other triggers). pHLH sHLH p value Outcomes MAS in sJIA sHLH from other triggers pHLH vs sHLH MAS vs sHLH (N = 5) (N = 6) (N = 37) PIM2 at PICU admission 2 19,6 (6,9–59) n = 4 2,1 (1,1–13,9) n = 3 8,2 (4,6–31,7) n = 14 0,57 0,36 Relapse of disease 1 1 (20,0) 4 (66,7) 7 (18,9) 1,0 0,029 PICU stay, days 2 24 (4–45) 19 (9–21) 19 (11–35) 0,88 0,61 PICU stay > 28 days 1 2 (40) 1 (16,7) 16 (43,2) 1,0 0,38 Death in PICU 1 3 (60) 0 (0) 13 (35,1) 0,275 0,097 1 Number (%) –Fisher's exact test; 2 Median (1st-3rd quartile) - Mann-Whitney test. Laboratory parameters at admission (T1) were compared across the 48 patients stratified by diagnosis (pHLH, MAS in sJIA, and sHLH from other triggers) (see Table 4 ). These included white blood cell count, neutrophils, platelets, ferritin, AST, ALT, LDH, triglycerides, fibrinogen, and D-dimers. Notably, white blood cell counts differed between survivors and non-survivors at PICU admission [5.34 × 10³/µL vs. 9.32 × 10³/µL; p = 0.076], as did neutrophil counts [0.9 × 10³/µL vs. 7.12 × 10³/µL; p = 0.012] (see Table 5 ). Table 4. Comparison of laboratory test values of 48 patients stratified by diagnosis (pHLH, MAS in sJIA and sHLH by other triggers). pHLH (N=5) sHLH Mann-Whitney U test MAS in sJIA (N=6) sHLH from other triggers (N=37) pHLH vs sHLH from other triggers MAS vs sHLH from other triggers Laboratory tests T1 T2 T1 T2 T1 T2 T1 T2 T1 T2 Median (Q1-Q3) Median (Q1-Q3) Median (Q1-Q3) Median (Q1-Q3) Median (Q1-Q3) Median (Q1-Q3) p value p value p value p value Ferritin (ng/ml) 7531 (4823-10860) 96360 (25986-120252) 8285 (242-53072) 36555 (18000-55000) 7326 (2020-12947) 22121 (8990-64120) 0,85 0,27 0,82 0,67 White blood cells (*10 3 /mcl) 0,69 (0,20-2,66) 0,71 (0,40-2,05) 18,29 (11,29-25,18) 10,19 (1,46-16,53) 7,08 (2,79-14,14) 5,41 (2,39-14,77) 0,015 0,046 0,023 0,86 Neutrophils (*10 3 /mcl) 0,13 (0,02-1,19) 0,12 (0,08-0,83) 12,54 (8,59-23,82) 5,37 (1,00-8,59) 4,16 (0,80-8,96) 3,44 (1,27-10,58) 0,0083 0,015 0,019 0,97 Platelets (*10 3 /mcl) 18 (10-55) 29 (23-63) 116 (103-128) 88 (44-177) 70 (34-168) 54 (28-103) 0,057 0,24 0,55 0,18 AST (UI/l) 131 (88-133) 438 (295-7990) 344 (31-1440) 831 (181-1512) 118 (45-609) 461 (158-1370) 0,85 0,47 0,85 1,0 ALT (UI/l) 102 (72-116) 128 (121-1688) 72 (40-161) 107 (28-817) 62 (28-191) 182 (80-657) 0,58 0,80 0,99 0,47 LDH (UI/l) 1082 (982-1335) 7661 (1402-15268) 5118 (983-9058) 5805 (1949-9350) 1653 (855-3669) 2505 (1396-5716) 0,26 0,39 0,21 0,41 Triglycerides (mg/dl) 565 (411-573) 208 (148-443) 226 (139-366) 332 (149-450) 231 (109-279) 262 (146-428) 0,030 0,78 0,69 0,73 Fibrinogen (mg/dl) 244 (229-259) 168 (103-199) 206 (146-488) 183 (159-200) 199 (150-328) 155 (94-241) 0,67 0,83 0,76 0,47 D-dimers (mcg/dl) 3,5 (3,4-11,8) 11,1 (1,7-20,0) 15,3 (6,9-20,0) 20,0 (3,6-20,0) 5,4 (2,6-20,0) 7,5 (2,7-19,7) 0,021 1,0 0,33 0,46 Legend: HLH = haemophagocytic lymphohistiocytosis (p = primary; s = secondary); MAS = macrophage activation syndrome; sJIA = systemic juvenile idiopathic arthritis; T1 = time of admission to intensive care; T2: moment with highest value of ferritinemia; AST = aspartate amino transferase; ALT = alanine amino transferase; LDH = lactate dehydrogenase. Table 5 Analysis of laboratory values of 48 patients stratified by survival in PICU. Laboratory tests NON-SURVIVORS (N = 16) SURVIVORS (N = 32) Mann-Whitney U test T1 T2 T1 T2 T1 T2 Mediana (Q1-Q3) Mediana (Q1-Q3) Mediana (Q1-Q3) Mediana (Q1-Q3) p value p value Ferritin (ng/ml) 11717 (7531–17271) 72290 (25517–124582) 3975 (1400–11360) 15200 (7062–45661) 0,069 0,010 White blood cells (*10 3 /mcl) 5,34 (0,69 − 9,15) 5,81 (0,83 − 14,16) 9,32 (3,18 − 17,40) 5,33 (1,94 − 12,60) 0,076 0,776 Neutrophils (*10 3 /mcl) 0,9 (0,12 − 4,7) 3,90 (0,80 − 7,63) 7,12 (1,97 − 12,91) 2,81 (1,04–8,17) 0,012 0,948 Platelets (*10 3 /mcl) 39 (32–150) 32 (15–58) 101 (40–134) 72 (33–132) 0,358 0,022 AST (UI/l) 142 (44–455) 658 (291–2602) 122 (57–602) 388 (107–996) 0,863 0,043 ALT (UI/l) 101 (41–171) 330 (158–1130) 52 (32–149) 121 (53–575) 0,501 0,025 LDH (UI/l) 1361 (689–2545) 3496 (1844–9692) 1766 (1033–4796) 2287 (985–5211) 0,144 0,103 Triglycerides (mg/dl) 262 (107–538) 262 (176–443) 239 (139–307) 298 (149–412) 0,976 0,951 Fibrinogen (mg/dl) 199 (150–254) 153 (102–203) 215 (150–334) 172 (117–247) 0,594 0,425 D-dimers (mcg/dl) 3,24 (2,64 − 6,50) 6,1 (2,7–20) 15,1 (3–20) 9 (2,5–20,0) 0,074 0,785 Legend : HLH = haemophagocytic lymphohistiocytosis (p = primary; s = secondary); MAS = macrophage activation syndrome; sJIA = systemic juvenile idiopathic arthritis; T1 = time of admission to intensive care; T2: moment with highest value of ferritinemia; AST = aspartate amino transferase; ALT = alanine amino transferase; LDH = lactate dehydrogenase. Platelet count, on the other hand, was similar at PICU admission (T1) but showed a significant difference at T2 [32,000 /µL vs. 72,000 /µL (p = 0.022)]. All patients received some form of mechanical ventilation; in 80% of cases, support was provided via invasive mechanical ventilation. Long-term mechanical ventilation (greater than 14 days) was necessary in 50% of pHLH patients, 60% of MAS patients, and 42.4% of sHLH patients. Regarding extracorporeal organ support, ECMO was used only in the sHLH group: one patient with MAS (support duration of 108 days) and nine cases among sHLH patients from other predisposing conditions (median duration of 7 days). Continuous renal replacement therapy (CRRT) was employed in 60% of pHLH cases, 50% of MAS cases, and 59.5% of sHLH cases, with median durations of 22, 21, and 16 days, respectively. Plasma exchange was used exclusively in the secondary HLH group: in 2 out of 6 MAS cases (33.3%) and in 14 out of 37 other sHLH cases (37.8%). Hemoadsorption, in combination with CRRT, was performed in one pHLH case and four sHLH cases, with a median duration of 72 hours. Long-term mechanical ventilation was observed in 37.5% of non-survivors compared to 40.6% of survivors. Additionally, ECMO support was provided to 25% of non-survivors versus 18.8% of survivors; the median duration of ECMO support was 7 days among non-survivors and 7.5 days among survivors. Table 6 reports the median duration of extracorporeal supports, distinguishing between survivors and non-survivors. A statistically significant difference was found in the duration of CRRT (p = 0.021) and the number of Hemoadsorption sessions (p = 0.037) between these groups. Table 6 Comparison of extracorporeal supports and outcomes of 48 patients stratified by survival. Extra-corporeal supports and outcomes Non-survivors (N = 16) Survivors (N = 32) p value Mechanical ventilation 1 16 (100) 26 (81,3) 0,159 F Duration (days) 2 13 (8–23) 13 (6–29) 0,969 ECMO 1 4 (25) 6 (18,8) 0,712 F Duration (days) 2 7,5 (2–16) 7 (6–54) 0,476 CRRT 1 13 (81,3%) 15 (46,9) 0,021 C Duration (days) 2 20 (10–30) 16 (10–31) 0,821 Plasma exchange 1 5 (31,3) 11 (34,4) 1,0 C Hemoadsorption 1 4 (25) 1 (6,3) 0,037 F PIM2 upon entering PICU 2 25 (10,1–64,8) 4,6 (2,1–13,6) 0,010 Relapse of disease 1 1 (6,3) 11 (34,4) 0,040 C Days in PICU 2 27 (16–37) 19 (9–36) 0,308 PICU stay > 28 days 1 8 (50) 11 (34,4) 0,307 C 1 Number (%) - Chi-square test C/ Fisher exact test F; 2 Median (1st-3rd quartile) - Mann-Whitney test. Mortality was higher among primary HLH (60%) and onco-hematological cases (100%). Secondary HLH cases showed a mortality rate of 35.1%, while MAS cases had no observed mortality (0%) in this study sample. MAS also exhibited a higher relapse rate (66.7%) compared to pHLH (20%) and sHLH (18.9%). DISCUSSION To the best of our knowledge, our study reports on the characteristics of one of the largest pediatric series of patients with pHLH and sHLH treated in the PICU setting. In our cohort, the distribution between males and females (22 vs. 26, respectively) was similar. We found that primary HLH forms tend to have an earlier onset in childhood, and among the secondary forms, infectious predisposition was the most common (48.8%). A previous study [ 19 ] reported an overall survival rate of 45%, with increased mortality associated with HLH triggered by infection or malignancy. However, differences in survival did not correlate with genetic profile or the extent of therapy. The same study [ 19 ] discusses how the uncertain performance of the HLH-2004 criteria and the consequences of missed or incorrect diagnoses have led to widely variable approaches to diagnosis and treatment [ 4 , 20 ]. These findings are consistent with our sample, where overall mortality in the PICU was high (33.3%), particularly in the primary HLH group (60%) and the onco-hematological group (100%), but no mortality was observed among the MAS group (0%). In our cohort, patients with the worst prognosis exhibited features such as splenomegaly at onset, lower platelet counts, and higher ferritin levels at PICU admission. Extracorporeal support therapies were used uniformly across all patients, but for longer durations in the most severe cases, which correlated with higher mortality. The higher mortality observed in primary HLH and sHLH related to onco-hematological disease may be linked to underlying genetic conditions that predispose these patients to early childhood risks, as well as to compromised general health and comorbidities in the latter group. Conversely, the more frequent relapses seen in the MAS group, with no associated mortality, likely reflect the classic pattern of recurrent exacerbations of rheumatological disorders. Early diagnosis and targeted therapies in patients with known diagnoses may also contribute to this trend. In our population, pHLH always presented with a full symptom complex. Fever was the most common clinical symptom, even in secondary forms. Splenomegaly and bone marrow hemophagocytosis were frequent but not universal. According to the literature [ 23 ], splenomegaly occurs in about 79% of HLH cases (survivors 84.85%, non-survivors 66.67%), likely due to immune activation, especially of lymphocytes and macrophages. In our study, splenomegaly at onset was more common in patients who died compared to those who survived (overall 58.3%, survivors 53.1%, non-survivors 68.8%). This suggests that more severe immune activation may lead to a more severe clinical presentation, with splenomegaly potentially serving as a negative prognostic factor. The incidence of multi-organ failure (MOF), central nervous system impairments, and renal dysfunction was higher among non-survivors, though these differences did not reach statistical significance. The length of PICU stay was shorter in the MAS group and longer in the other groups. The hepatobiliary damage (HBD) score changed from T1 to T2, worsening in the pHLH group (which showed no alterations at T1), improving among MAS patients, and worsening in other sHLH cases—indicating a greater involvement of the hepatobiliary system in secondary non-rheumatologic forms of HLH. The Pediatric Index of Mortality 2 (PIM2) at T1 was higher in pHLH (19.6%), lower in sHLH (8.2%), and much lower in MAS (2.1%). PIM2 was also significantly higher among non-survivors (25% vs. 4.6%; p = 0.01; see Table 6 ). This finding suggests that PIM2 could serve as a reliable prognostic tool. Ferritin levels at T1 were similar across pHLH, sHLH, and MAS; however, at T2, ferritin levels were higher in pHLH, lower in MAS, and much lower in other sHLH cases. Ferritin levels were approximately three times higher among non-survivors compared to survivors at T1 (p = 0.069) and about twice as high at T2 (p = 0.01), confirming that ferritin functions as a prognostic biomarker in HLH [ 3 , 16 , 17 ]. Regarding white blood cell counts, we observed differences among MAS, sHLH, and pHLH, but values remained within the normal range for both survivors and non-survivors. Therefore, white blood cell count does not appear to be useful for predicting severity. In contrast, platelet counts were lower among non-survivors at both T1 and T2, indicating that this parameter could help identify patients at higher risk of death. This trend of decreasing platelets and white blood cells may reflect a better disease status at T1 in some patients, while the uniformity of worse values at T2 across groups likely indicates clinical worsening. LDH levels were elevated in all groups. In pHLH patients, LDH increased from three times the upper normal limit at T1 to twenty times at T2. In MAS patients, LDH remained consistently high (about 17 times the normal), while in sHLH patients, it increased from 5 to 8 times from T1 to T2. Extracorporeal support techniques played a significant role in our patient management, especially considering that this study was conducted in the PICU setting, where all patients had severe HLH, rapidly evolving clinical conditions, or hemodynamic instability. Patients with more severe conditions required extracorporeal support more frequently and for longer durations. Often, a combination of techniques was used (e.g., invasive mechanical ventilation, CRRT, ECMO, plasma exchange, hemoadsorption). All patients with pHLH initially received non-invasive ventilation, and most patients with pHLH, MAS, and sHLH also required invasive mechanical ventilation. Interestingly, long-term mechanical ventilation (more than 14 days) was associated with survival in our cohort. ECMO was used only in the sHLH group (a total of 10 patients, with only one patient having MAS), with a median duration of 7 days. ECMO was applied at similar rates among survivors (18.8%) and non-survivors (25%), with the same median duration (7 vs. 7.5 days). However, the mean duration was about three times longer in non-survivors (10.5 vs. 33.3 days). Renal replacement therapy (CRRT) was more frequently required in non-survivors (81.3%) compared to survivors (46.9%), and for longer periods (20 vs. 16 days). Plasma exchange was performed only in MAS and sHLH groups, at similar rates among survivors (34.4%) and non-survivors (31.3%). Hemoadsorption with CytoSorb was used in one case of pHLH and in four cases of sHLH, mainly among non-survivors (6.3% vs. 25%). The high incidence of extracorporeal therapies and mechanical ventilation in our cohort of critically ill children admitted to the PICU reflects the complexity of these patients and the high prevalence of organ dysfunction associated with HLH as a hyperinflammatory syndrome. CONCLUSIONS Hemophagocytic lymphohistiocytosis (HLH) is associated with high mortality despite intensive care and maximal therapeutic support. Mortality is particularly elevated in patients with primary HLH and those with onco-hematological forms. While MAS patients were prone to relapse, no deaths occurred in this subgroup during the study period. Early presence of splenomegaly, low platelet count, and elevated ferritin levels at PICU admission are potential predictors of adverse outcomes. The PIM2 score may serve as a useful prognostic tool in HLH. Extracorporeal support therapies—including ECMO, invasive mechanical ventilation, continuous renal replacement therapy (CRRT), plasma exchange, and CytoSorb—were applied consistently across patients, though for longer durations in the most severe cases, which correlated with higher mortality. To our knowledge, this is one of the largest pediatric cohorts of patients with both primary and secondary HLH treated in a PICU setting. Abbreviations CMV: cytomegalovirus CRRT: Continuous Renal Replacement Therapy DIC: diffuse intravascular coagulation EBV: Epstein-Barr virus ECMO: extracorporeal membrane oxygenation HBD: hepatobiliary damage HLH: hemophagocytic lymphohistiocytosis MAS: macrophage activation syndrome MOF: multiple organ failure MV: mechanical ventilation pHLH: primary hemophagocytic lymphohistiocytosis PICU: pediatric intensive care unit PIM2: Pediatric Index of Mortality sHLH: secondary hemophagocytic lymphohistiocytosis sJIA: systemic juvenile idiopathic arthritis SLE: systemic lupus erythematosus SPENCD: Spondyloenchondrodysplasia Declarations Ethics approval and consent to participate: The study received approval from the Institutional Review Board of Children Hospital Bambino Gesù. Informed consent was waived due to the retrospective nature of the study. This study was performed in line with the principles of the Declaration of Helsinki. This is an observational study. Approval was granted by the Ethics Committee of Bambino Gesù Children's Hospital, IRCCS, Rome. Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding: All phases of this study were supported by Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. This work was supported by the Italian Ministry of Health with Current Research funds. Authors' contributions: MM, GB, CB and MDN conceptualized and designed the study, coordinate and supervised collected data and drafted the initial manuscript; FC, FDL, PM conceptualized and designed the study, coordinate and supervised collected data, and drafted the initial manuscript; DPM, collaborate to the design of the study and performed all statistical analyses, contributed to manuscript drafting, critically reviewed and revised the manuscript; MM, GB, CB, MDN, FC, FDL and PM collaborate to the design of the study, contributed to manuscript drafting, critically reviewed and revised the manuscript; CC and FDB designed the study, supervised data collection, and reviewed and revised the manuscript for important intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Acknowledgements: Not applicable. References Joseph A, Carcillo B, Shakoory D, Simon. Kate Kernan. Understanding Disseminated Intravascular Coagulation and Hepatobiliary Dysfunction Multiple Organ Failure in Hyperferritinemic Critical Illness. Pediatric Critical Care Medicine, October 2018 • Volume 19 • Number 10. 10.1097/PCC.0000000000001712 Ravelli A, Grom AA, Behrens EM, Cron RQ. Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment. Genes Immun. 2012;13:289–98. Janka G, Imashuku S, Elinder G, Schneider M, Henter JI. Infection and malignancy associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am. 1998;12:435–44. Castillo L, Carcillo J. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/ systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med. 2009;10(3):387–92. 10.1097/PCC.0b013e3181a1ae08 . PMID:19325510. Janka GE. Familial hemophagocytic lymphohistiocytosis., Eur JP. 1983 Jun-Jul;140(3):221 – 30. 10.1007/BF00443367 . PMID: 6354720. Janka GE. Hemophagocytic syndromes. Blood Rev. 2007;21:245–53. Larroche C, Mouthon L. Pathogenesis of hemophagocytic syndrome (HPS). Autoimmun Rev. 2004;3:69–75. Grom A, Horne A AC and, De Benedetti F. Macrophage activation syndrome in the era of biologic therapy. Nat Reviews Rheumatol volume. 2016;12:pages259–268. Bracaglia C, Prencipe G, De Benedetti F, Bracaglia, et al. Pediatr Rheumatol. 2017;15:5. 10.1186/s12969-016-0130-4 . Ishii E, Ohga S, Imashuku S, et al. Review of hemophagocytic lymphohistiocytosis (HLH) in children with focus on Japanese experiences. Crit Rev Oncol Hematol. 2005;53:209–23. Marcenaro S, Gallo F, Martini S, et al. Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease. Blood. 2006;108:2316–23. Joseph A, Carcillo B, Shakoory D, Simon. Kate Kernan. Understanding Disseminated Intravascular Coagulation and Hepatobiliary Dysfunction Multiple Organ Failure in Hyperferritinemic Critical Illness. Pediatric Critical Care Medicine, October 2018 • Volume 19 • Number 10. 10.1097/PCC.0000000000001712 Goldman J, Desai MS, McClain KL, et al. Hepatobiliary Dysfunction and Disseminated Intravascular Coagulation Increase Risk of Mortality in Pediatric Hemophagocytic Lymphohistiocytosis. Ped Crit Care Med. 2018;19:e522–30. Kyriazopoulou E, Leventogiannis K, Norrby-Teglund A, Hellenic Sepsis Study Group, et al. Macrophage activation-like syndrome: An immunological entity associated with rapid progression to death in sepsis. BMC Med. 2017;15:172. Machowicz R, Jankab G, Wiktor-Jedrzejczak W. Similar but not the same: Differential diagnosis of HLH and sepsis. Crit Rev Oncol/Hematol. 2017;114:1–12. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124 – 31. 10.1002/pbc.21039 . PMID: 16937360. Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, Aricò M, Avcin T, Behrens EM, De Benedetti F, Filipovic L, Grom AA, Henter JI, Ilowite NT, Jordan MB, Khubchandani R, Kitoh T, Lehmberg K, Lovell DJ, Miettunen P, Nichols KE, Ozen S, Pachlopnik Schmid J, Ramanan AV, Russo R, Schneider R, Sterba G, Uziel Y, Wallace C, Wouters C, Wulffraat N, Demirkaya E, Brunner HI, Martini A, Ruperto N, Cron RQ. Paediatric Rheumatology International Trials Organisation; Childhood Arthritis and Rheumatology Research Alliance; Pediatric Rheumatology Collaborative Study Group; Histiocyte Society. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol. 2016;68(3):566–76. 10.1002/art.39332 . Epub 2016 Feb 9. PMID: 26314788. Goldman J, Desai MS, McClain KL, Tcharmtchi MH, Kennedy CE, Thompson K, Lam F, Bashir DA, Chinn IK, Goldberg BR, Allen CE, Nguyen TC. Hepatobiliary Dysfunction and Disseminated Intravascular Coagulation Increase Risk of Mortality in Pediatric Hemophagocytic Lymphohistiocytosis. Pediatr Crit Care Med. 2018;19(10):e522–30. 10.1097/PCC.0000000000001684 . PMID: 30113519; PMCID: PMC9097722. Chinn IK, Eckstein OS, Peckham-Gregory EC, Goldberg BR, Forbes LR, Nicholas SK, Mace EM, Vogel TP, Abhyankar HA, Diaz MI, Heslop HE, Krance RA, Martinez CA, Nguyen TC, Bashir DA, Goldman JR, Stray-Pedersen A, Pedroza LA, Poli MC, Aldave-Becerra JC, McGhee SA, Al-Herz W, Chamdin A, Coban-Akdemir ZH, Jhangiani SN, Muzny DM, Cao TN, Hong DN, Gibbs RA, Lupski JR, Orange JS, McClain KL, Allen CE. Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis. Blood. 2018;132(1):89–100. 10.1182/blood-2017-11-814244 . Epub 2018 Apr 9. PMID: 29632024; PMCID: PMC6034641. Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041-52. doi: 10.1182/blood-2011-03-278127. Epub 2011 Aug 9. PMID: 21828139; PMCID: PMC3204727. Henter JI, Elinder G. Familial hemophagocytic lymphohistiocytosis. Clinical review based on the findings in seven children. Acta Paediatr Scand. 1991;80(3):269 – 77. 10.1111/j.1651-2227.1991.tb11849.x . PMID: 2035321. Imashuku S, Kuriyama K, Teramura T, Ishii E, Kinugawa N, Kato M, Sako M, Hibi S. Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Clin Oncol. 2001;19(10):2665-73. 10.1200/JCO.2001.19.10.2665 . PMID: 11352958. Yu TY, Lu MY, Lin KH, Chang HH, Chou SW, Lin DT, Jou ST, Yang YL. Outcomes and prognostic factors associated with 180-day mortality in Taiwanese pediatric patients with Hemophagocytic Lymphohistiocytosis. J Formos Med Assoc. 2021;120(4):1061–8. Epub 2020 Nov 17. PMID: 33218852. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 18 Jan, 2026 Reviews received at journal 15 Jan, 2026 Reviews received at journal 08 Jan, 2026 Reviewers agreed at journal 02 Dec, 2025 Reviewers agreed at journal 02 Dec, 2025 Reviewers invited by journal 02 Dec, 2025 Editor assigned by journal 02 Dec, 2025 Submission checks completed at journal 02 Dec, 2025 First submitted to journal 26 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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lymphohistiocytosis (HLH) is a challenging and potentially life-threatening condition characterized by an uncontrolled inflammatory response resulting from hyperactivation of T lymphocytes and macrophages, leading to excessive production of inflammatory cytokines. The main clinical features include fever, lymphadenopathy, hepatosplenomegaly, coagulopathy, and dysfunction of the renal, hepatic, and central nervous systems. Refractory HLH to medical therapy may progress to multiple organ failure (MOF) and death in a significant proportion of cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTypical laboratory findings encompass cytopenia affecting one or more cell lines (anemia, leukopenia, and thrombocytopenia), elevated transaminases, lactate dehydrogenase (LDH), ferritin, D-dimers, and decreased fibrinogen levels [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. HLH can be classified as primary (pHLH), also known as familial HLH, or secondary (sHLH), also referred to as reactive HLH. pHLH results from genetic defects involved in the cytotoxic pathway, whereas sHLH can be triggered by various conditions such as infections, rheumatological diseases, and malignancies. However, in a notable percentage of cases, no specific trigger can be identified [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eInfectious triggers are predominantly herpesviruses, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV), as well as influenza viruses (notably H1N1) and Leishmania. Rheumatological diseases are also common triggers of sHLH, particularly systemic juvenile idiopathic arthritis (sJIA), systemic lupus erythematosus (SLE), Kawasaki disease, and systemic vasculitis. These forms are often referred to as macrophage activation syndrome (MAS) [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Other predisposing conditions include malignancies (most frequently lymphoma and leukemia), immunological disorders, and metabolic diseases. In 15\u0026ndash;40% of cases, no identifiable trigger for sHLH can be determined [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSevere forms of HLH may necessitate admission to the PICU and the use of advanced organ support [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In this context, accurate differential diagnosis from acute conditions such as sepsis\u0026mdash;which requires entirely different treatment strategies\u0026mdash;is essential to improve patient outcomes [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Therefore, the primary objective of this study is to describe the clinical characteristics, risk factors\u0026mdash;including the need for extracorporeal therapies\u0026mdash;laboratory parameters, and prognostic outcomes (such as duration of mechanical ventilation, length of PICU stay, and survival) of patients admitted to the PICU with HLH. Additionally, the study aims to identify early predictors of clinical outcomes.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e We conducted a retrospective review of all patients with primary and secondary HLH who required PICU admission from 2006 to 2019. The diagnosis of HLH was based on the HLH-2004 diagnostic guidelines and the MAS-2016 classification criteria [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The study received approval from the Institutional Review Board of Children Hospital Bambino Ges\u0026ugrave;. Informed consent was waived due to the retrospective nature of the study.\u003c/p\u003e\u003cp\u003eClinical features, laboratory parameters, and supportive therapies were extracted from electronic medical records. Patients were evaluated at two time points: at PICU admission (T1) and at the time of the highest ferritin level (T2) during their PICU stay. The risk of mortality was assessed using the Pediatric Index of Mortality (PIM2) score at PICU admission (T1). Organ dysfunction was evaluated using the hepato-biliary dysfunction and diffuse intravascular coagulation (DIC) scores [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe primary objective was to describe the clinical and laboratory parameters related to HLH, as well as prognostic outcomes, comparing survivors and non-survivors after PICU admission. Mortality was defined as death occurring during the PICU stay.\u003c/p\u003e\u003cp\u003eWe considered the following risk factors for mortality in our population: invasive mechanical ventilation (MV), extracorporeal organ support (including extracorporeal membrane oxygenation, ECMO), and extracorporeal blood purification techniques (such as Continuous Renal Replacement Therapy, CRRT; hemoadsorption; and plasma exchange). Additionally, we evaluated complications as potential risk factors for mortality, including disseminated intravascular coagulation, hepatobiliary dysfunction, and central nervous system involvement during PICU stay.\u003c/p\u003e\u003cp\u003eDescriptive statistics were employed in this study. The distribution of the variables under investigation was assessed using the Shapiro-Wilk test, along with measures of skewness and kurtosis. Since the primary variables did not follow a Gaussian distribution, continuous data were summarized using medians and interquartile ranges (first and third quartiles) and compared with the Mann-Whitney U test. Categorical variables were expressed as absolute and percentage frequencies, with group comparisons performed using the Chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. A p-value of less than 0.05 (two-tailed) was considered statistically significant. Data were stored in an Excel database, and all statistical analyses were conducted using Stata software version 15.1 (StataCorp, College Station, TX).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e48 patients were included in this study. Baseline clinical characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The sample comprised 22 females (45.8%) and 26 males (54.2%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of the 48 patients stratified by diagnosis (pHLH, MAS in sJIA and sHLH by other triggers).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003epHLH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003esHLH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMAS in sJIA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003esHLH from other triggers\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003epHLH\u003c/p\u003e\u003cp\u003evs\u003c/p\u003e\u003cp\u003esHLH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMAS\u003c/p\u003e\u003cp\u003evs\u003c/p\u003e\u003cp\u003esHLH\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, Females \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (40,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (66,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (43,2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1,0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at onset (years) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,0 (0,6\u0026thinsp;\u0026minus;\u0026thinsp;1,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8,5 (1,8\u0026ndash;12,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5,6 (1,2\u0026ndash;11,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,068\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,57\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at PICU admission (years) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,8 (1,2\u0026ndash;3,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8,5 (1,8\u0026ndash;13,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5,5 (2,6\u0026ndash;11,5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,095\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0,56\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTrigger \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOnco-Hematological\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (5,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfectious\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21 (56,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRheumatological\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (21,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUndefined\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (16,2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMAS criteria\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCriteria HLH-2004\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30 (81,1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0,57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e1\u003c/sup\u003eNumber (%) \u0026ndash;Fisher's exact test; \u003csup\u003e2\u003c/sup\u003eMedian (1st-3rd quartile) - Mann-Whitney test.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePatients with secondary hemophagocytic lymphohistiocytosis (sHLH) were stratified according to their predisposing conditions. In two patients (4.7%), the predisposing condition was a hematological disease\u0026mdash;specifically, primary combined immunodeficiency and Hodgkin\u0026rsquo;s lymphoma.\u003c/p\u003e\u003cp\u003eIn 21 patients (48.8%), the predisposing factor was an infection, including one case of Leishmania, viral agents in 12 patients (Rhinovirus, H1N1, EBV, HHV6, VZV, Bocavirus), and bacterial etiology in 8 patients.\u003c/p\u003e\u003cp\u003eFourteen patients (32.6%) had a rheumatological disease as the predisposing factor, with specific diagnoses including five cases of systemic juvenile idiopathic arthritis (sJIA), two with NLRC4-gain of function, one with systemic lupus erythematosus (SLE), one with Kawasaki syndrome, one with an interferonopathy (spondyloenchondrodysplasia, SPENCD), one with Rasmussen syndrome, one with antiphospholipid antibody syndrome, and one with ANCA-positive vasculitis. In 56.8% of cases, HLH was triggered by an infectious event (e.g., EBV, CMV, H1N1, sepsis).\u003c/p\u003e\u003cp\u003eThe different forms of HLH showed varying ages at disease onset: primary HLH (pHLH) at approximately 1 year, macrophage activation syndrome (MAS) in sJIA at around 8.5 years, and sHLH at about 5.6 years.\u003c/p\u003e\u003cp\u003eAll patients with pHLH presented with fever, splenomegaly, and hemophagocytosis observed in bone marrow aspirates. Conversely, in sHLH, fever was the most common clinical symptom (94.6%), followed by splenomegaly in 56.8% of cases and in 33.3% of MAS cases. Hemophagocytosis in bone marrow was observed in 76% of sHLH cases and 60% of MAS cases (see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDescription of symptoms and organ damage of the 48 patients stratified by diagnosis (pHLH, MAS in sJIA and sHLH by other triggers).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003epHLH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003esHLH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSymptoms and organ damage\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMAS in sJIA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003esHLH from other triggers\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003epHLH\u003c/p\u003e\u003cp\u003evs\u003c/p\u003e\u003cp\u003esHLH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMAS\u003c/p\u003e\u003cp\u003evs\u003c/p\u003e\u003cp\u003esHLH\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFever\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (83,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35 (94,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1,0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,37\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSplenomegaly\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (33,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21 (56,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0,14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemophagocytosis\u003c/p\u003e\u003cp\u003e(Bone marrow aspirate or biopsy)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4/4 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3/5 (60,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19/25 (76,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0,55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,64\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCentral Nervous System involvement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (40,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (33,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 (64,9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0,35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMulti-organ failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (40,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (16,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (37,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1,0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcute kidney injury\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (40,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (16,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17 (46,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1,0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBD at PICU admission\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (50,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (51,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0,053\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1,0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHBD at T2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (40,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (16,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (70,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0,31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0,021\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eLegend: HBD\u0026thinsp;=\u0026thinsp;hepato-biliary dysfunction.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eRelapse of disease, defined as a new HLH episode during PICU stay, occurred in 20% of pHLH patients, 66.7% of MAS patients with sJIA, and 18.9% of sHLH patients from other predisposing conditions. The difference between MAS and sHLH relapse rates was statistically significant (p\u0026thinsp;=\u0026thinsp;0.029; see Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e also details the Pediatric Index of Mortality 2 (PIM2) scores at T1, length of PICU stay, and mortality rates.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOutcomes of the 48 patients stratified by diagnosis (pHLH, MAS in sJIA and sHLH by other triggers).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003epHLH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003esHLH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMAS in sJIA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003esHLH from other triggers\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003epHLH\u003c/p\u003e\u003cp\u003evs\u003c/p\u003e\u003cp\u003esHLH\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMAS\u003c/p\u003e\u003cp\u003evs\u003c/p\u003e\u003cp\u003esHLH\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIM2 at PICU admission\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19,6\u003c/p\u003e\u003cp\u003e(6,9\u0026ndash;59)\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2,1\u003c/p\u003e\u003cp\u003e(1,1\u0026ndash;13,9)\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8,2\u003c/p\u003e\u003cp\u003e(4,6\u0026ndash;31,7)\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0,57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,36\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRelapse of disease \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (20,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (66,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (18,9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1,0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0,029\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePICU stay, days\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (4\u0026ndash;45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (9\u0026ndash;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (11\u0026ndash;35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0,88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePICU stay\u0026thinsp;\u0026gt;\u0026thinsp;28 days\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (16,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (43,2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1,0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeath in PICU\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (35,1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0,275\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,097\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003e1\u003c/sup\u003eNumber (%) \u0026ndash;Fisher's exact test; \u003csup\u003e2\u003c/sup\u003eMedian (1st-3rd quartile) - Mann-Whitney test.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eLaboratory parameters at admission (T1) were compared across the 48 patients stratified by diagnosis (pHLH, MAS in sJIA, and sHLH from other triggers) (see Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). These included white blood cell count, neutrophils, platelets, ferritin, AST, ALT, LDH, triglycerides, fibrinogen, and D-dimers. Notably, white blood cell counts differed between survivors and non-survivors at PICU admission [5.34 \u0026times; 10\u0026sup3;/\u0026micro;L vs. 9.32 \u0026times; 10\u0026sup3;/\u0026micro;L; p\u0026thinsp;=\u0026thinsp;0.076], as did neutrophil counts [0.9 \u0026times; 10\u0026sup3;/\u0026micro;L vs. 7.12 \u0026times; 10\u0026sup3;/\u0026micro;L; p\u0026thinsp;=\u0026thinsp;0.012] (see Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:justify;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eTable 4. \u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eComparison of laboratory test values of 48 patients stratified by diagnosis (pHLH, MAS in sJIA and sHLH by other triggers).\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:100.0%;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:8.98%;border:solid windowtext 1.0pt;border-bottom: none;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" style=\"width:22.34%;border:solid windowtext 1.0pt;border-left:none;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003epHLH\u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;(N=5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width:47.02%;border:solid windowtext 1.0pt;border-left:none;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003esHLH\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 21.64%;border-top: 1pt solid windowtext;border-right: 1pt solid windowtext;border-bottom: 1pt solid windowtext;border-image: initial;border-left: none;padding: 0in 5.4pt;height: 14.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eMann-Whitney \u003cem\u003eU\u003c/em\u003e test\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height:14.2pt;border:none;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:8.98%;border-top:none;border-left:solid windowtext 1.0pt;border-bottom:none;border-right:solid windowtext 1.0pt;padding: 0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width:22.34%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eMAS in sJIA \u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e(N=6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width:24.68%;border:solid windowtext 1.0pt;border-left:none;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003esHLH from other triggers \u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e(N=37)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 11%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 14.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003epHLH vs\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003esHLH from other triggers\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 10.66%;border-top: none;border-left: none;border-bottom: 1pt solid windowtext;border-right: 1pt solid windowtext;padding: 0in 5.4pt;height: 14.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eMAS vs\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003esHLH from other triggers\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height:14.2pt;border:none;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:8.98%;border-top:none;border-left:solid windowtext 1.0pt;border-bottom:none;border-right:solid windowtext 1.0pt;padding: 0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eLaboratory tests\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height:14.2pt;border:none;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:11.12%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFE599;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT1\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.22%;border:solid windowtext 1.0pt;border-left: none;background:#C5E0B3;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT2\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.16%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFE599;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT1\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.18%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#C5E0B3;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT2\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.26%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFE599;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT1\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.42%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#C5E0B3;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT2\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFE599;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT1\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border-top:none;border-left:none;border-bottom: solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background: #C5E0B3;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT2\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFE599;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT1\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.16%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#C5E0B3;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eT2\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height:14.2pt;border:none;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:8.98%;border:solid windowtext 1.0pt;border-top: none;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.12%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFE599;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eMedian\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(Q1-Q3)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.22%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#C5E0B3;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eMedian\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(Q1-Q3)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.16%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFE599;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eMedian\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(Q1-Q3)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.18%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#C5E0B3;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eMedian\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(Q1-Q3)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.26%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFE599;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eMedian\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(Q1-Q3)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.42%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#C5E0B3;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003eMedian\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(Q1-Q3)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFE599;padding:0in 5.4pt 0in 5.4pt;height:14.2pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003ep value\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border-top:none;border-left:none;border-bottom: solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background: #C5E0B3;padding:0in 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style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e0,69\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.16%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#E2EFD9;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e0,73\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height:24.1pt;border:none;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:8.98%;border:solid windowtext 1.0pt;border-top: none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eFibrinogen (mg/dl)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.12%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFF2CC;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e244\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(229-259)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.22%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid 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style=\"width:12.26%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFF2CC;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e199\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(150-328)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.42%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#E2EFD9;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e155\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(94-241)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFF2CC;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e0,67\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border-top:none;border-left:none;border-bottom: solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background: #E2EFD9;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e0,83\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFF2CC;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e0,76\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.16%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#E2EFD9;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e0,47\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height:24.1pt;border:none;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:8.98%;border:solid windowtext 1.0pt;border-top: none;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003eD-dimers\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;'\u003e(mcg/dl)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.12%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFF2CC;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e3,5\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(3,4-11,8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.22%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#E2EFD9;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e11,1\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(1,7-20,0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.16%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFF2CC;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e15,3\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(6,9-20,0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.18%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#E2EFD9;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e20,0\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(3,6-20,0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.26%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFF2CC;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e5,4\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(2,6-20,0)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.42%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#E2EFD9;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e7,5\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e(2,7-19,7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFF2CC;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e0,021\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border-top:none;border-left:none;border-bottom: solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background: #E2EFD9;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e1,0\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.5%;border:none;border-bottom:solid windowtext 1.0pt;background:#FFF2CC;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e0,33\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:5.16%;border-top:none;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt;background:#E2EFD9;padding:0in 5.4pt 0in 5.4pt;height:24.1pt;\"\u003e\n \u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:center;border:none;'\u003e\u003cspan style='font-size:8px;font-family:\"Times New Roman\",serif;color:black;'\u003e0,46\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"height:24.1pt;border:none;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;font-size:13px;font-family:\"Arial\",sans-serif;text-align:justify;border:none;'\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eLegend: \u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-family:\"Times New Roman\",serif;'\u003eHLH = haemophagocytic lymphohistiocytosis (p = primary; s = secondary); MAS = macrophage activation syndrome; sJIA = systemic juvenile idiopathic arthritis; T1 = time of admission to intensive care; T2: moment with highest value of ferritinemia; AST = aspartate amino transferase; ALT = alanine amino transferase; LDH = lactate dehydrogenase.\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAnalysis of laboratory values of 48 patients stratified by survival in PICU.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eLaboratory tests\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eNON-SURVIVORS (N\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eSURVIVORS (N\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eMann-Whitney\u003cem\u003eU\u003c/em\u003e test\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eT1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eT2\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMediana\u003c/p\u003e\u003cp\u003e(Q1-Q3)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMediana\u003c/p\u003e\u003cp\u003e(Q1-Q3)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMediana\u003c/p\u003e\u003cp\u003e(Q1-Q3)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMediana\u003c/p\u003e\u003cp\u003e(Q1-Q3)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFerritin\u003c/p\u003e\u003cp\u003e(ng/ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11717\u003c/p\u003e\u003cp\u003e(7531\u0026ndash;17271)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e72290\u003c/p\u003e\u003cp\u003e(25517\u0026ndash;124582)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3975\u003c/p\u003e\u003cp\u003e(1400\u0026ndash;11360)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e15200\u003c/p\u003e\u003cp\u003e(7062\u0026ndash;45661)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,069\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0,010\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite blood cells (*10\u003csup\u003e3\u003c/sup\u003e/mcl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5,34\u003c/p\u003e\u003cp\u003e(0,69\u0026thinsp;\u0026minus;\u0026thinsp;9,15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5,81\u003c/p\u003e\u003cp\u003e(0,83\u0026thinsp;\u0026minus;\u0026thinsp;14,16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9,32\u003c/p\u003e\u003cp\u003e(3,18\u0026thinsp;\u0026minus;\u0026thinsp;17,40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e5,33\u003c/p\u003e\u003cp\u003e(1,94\u0026thinsp;\u0026minus;\u0026thinsp;12,60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,076\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0,776\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophils (*10\u003csup\u003e3\u003c/sup\u003e/mcl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0,9\u003c/p\u003e\u003cp\u003e(0,12\u0026thinsp;\u0026minus;\u0026thinsp;4,7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3,90\u003c/p\u003e\u003cp\u003e(0,80\u0026thinsp;\u0026minus;\u0026thinsp;7,63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7,12\u003c/p\u003e\u003cp\u003e(1,97\u0026thinsp;\u0026minus;\u0026thinsp;12,91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2,81\u003c/p\u003e\u003cp\u003e(1,04\u0026ndash;8,17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0,012\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0,948\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets\u003c/p\u003e\u003cp\u003e(*10\u003csup\u003e3\u003c/sup\u003e/mcl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e39\u003c/p\u003e\u003cp\u003e(32\u0026ndash;150)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32\u003c/p\u003e\u003cp\u003e(15\u0026ndash;58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e101\u003c/p\u003e\u003cp\u003e(40\u0026ndash;134)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e72\u003c/p\u003e\u003cp\u003e(33\u0026ndash;132)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,358\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0,022\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST\u003c/p\u003e\u003cp\u003e(UI/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e142\u003c/p\u003e\u003cp\u003e(44\u0026ndash;455)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e658\u003c/p\u003e\u003cp\u003e(291\u0026ndash;2602)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e122\u003c/p\u003e\u003cp\u003e(57\u0026ndash;602)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e388\u003c/p\u003e\u003cp\u003e(107\u0026ndash;996)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,863\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0,043\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u003c/p\u003e\u003cp\u003e(UI/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e101\u003c/p\u003e\u003cp\u003e(41\u0026ndash;171)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e330\u003c/p\u003e\u003cp\u003e(158\u0026ndash;1130)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e52\u003c/p\u003e\u003cp\u003e(32\u0026ndash;149)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e121\u003c/p\u003e\u003cp\u003e(53\u0026ndash;575)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,501\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0,025\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDH\u003c/p\u003e\u003cp\u003e(UI/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1361\u003c/p\u003e\u003cp\u003e(689\u0026ndash;2545)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3496\u003c/p\u003e\u003cp\u003e(1844\u0026ndash;9692)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1766\u003c/p\u003e\u003cp\u003e(1033\u0026ndash;4796)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2287\u003c/p\u003e\u003cp\u003e(985\u0026ndash;5211)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,144\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0,103\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTriglycerides (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e262\u003c/p\u003e\u003cp\u003e(107\u0026ndash;538)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e262\u003c/p\u003e\u003cp\u003e(176\u0026ndash;443)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e239\u003c/p\u003e\u003cp\u003e(139\u0026ndash;307)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e298\u003c/p\u003e\u003cp\u003e(149\u0026ndash;412)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,976\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0,951\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrinogen\u003c/p\u003e\u003cp\u003e(mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e199\u003c/p\u003e\u003cp\u003e(150\u0026ndash;254)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e153\u003c/p\u003e\u003cp\u003e(102\u0026ndash;203)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e215\u003c/p\u003e\u003cp\u003e(150\u0026ndash;334)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e172\u003c/p\u003e\u003cp\u003e(117\u0026ndash;247)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,594\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0,425\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eD-dimers\u003c/p\u003e\u003cp\u003e(mcg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3,24\u003c/p\u003e\u003cp\u003e(2,64\u0026thinsp;\u0026minus;\u0026thinsp;6,50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6,1\u003c/p\u003e\u003cp\u003e(2,7\u0026ndash;20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e15,1\u003c/p\u003e\u003cp\u003e(3\u0026ndash;20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e9\u003c/p\u003e\u003cp\u003e(2,5\u0026ndash;20,0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0,074\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0,785\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cb\u003eLegend\u003c/b\u003e: HLH\u0026thinsp;=\u0026thinsp;haemophagocytic lymphohistiocytosis (p\u0026thinsp;=\u0026thinsp;primary; s\u0026thinsp;=\u0026thinsp;secondary); MAS\u0026thinsp;=\u0026thinsp;macrophage activation syndrome; sJIA\u0026thinsp;=\u0026thinsp;systemic juvenile idiopathic arthritis; T1\u0026thinsp;=\u0026thinsp;time of admission to intensive care; T2: moment with highest value of ferritinemia; AST\u0026thinsp;=\u0026thinsp;aspartate amino transferase; ALT\u0026thinsp;=\u0026thinsp;alanine amino transferase; LDH\u0026thinsp;=\u0026thinsp;lactate dehydrogenase.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePlatelet count, on the other hand, was similar at PICU admission (T1) but showed a significant difference at T2 [32,000 /\u0026micro;L vs. 72,000 /\u0026micro;L (p\u0026thinsp;=\u0026thinsp;0.022)]. All patients received some form of mechanical ventilation; in 80% of cases, support was provided via invasive mechanical ventilation. Long-term mechanical ventilation (greater than 14 days) was necessary in 50% of pHLH patients, 60% of MAS patients, and 42.4% of sHLH patients.\u003c/p\u003e\u003cp\u003eRegarding extracorporeal organ support, ECMO was used only in the sHLH group: one patient with MAS (support duration of 108 days) and nine cases among sHLH patients from other predisposing conditions (median duration of 7 days). Continuous renal replacement therapy (CRRT) was employed in 60% of pHLH cases, 50% of MAS cases, and 59.5% of sHLH cases, with median durations of 22, 21, and 16 days, respectively. Plasma exchange was used exclusively in the secondary HLH group: in 2 out of 6 MAS cases (33.3%) and in 14 out of 37 other sHLH cases (37.8%). Hemoadsorption, in combination with CRRT, was performed in one pHLH case and four sHLH cases, with a median duration of 72 hours.\u003c/p\u003e\u003cp\u003eLong-term mechanical ventilation was observed in 37.5% of non-survivors compared to 40.6% of survivors. Additionally, ECMO support was provided to 25% of non-survivors versus 18.8% of survivors; the median duration of ECMO support was 7 days among non-survivors and 7.5 days among survivors.\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e reports the median duration of extracorporeal supports, distinguishing between survivors and non-survivors. A statistically significant difference was found in the duration of CRRT (p\u0026thinsp;=\u0026thinsp;0.021) and the number of Hemoadsorption sessions (p\u0026thinsp;=\u0026thinsp;0.037) between these groups.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of extracorporeal supports and outcomes of 48 patients stratified by survival.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtra-corporeal supports and outcomes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNon-survivors (N\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSurvivors (N\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMechanical ventilation \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (81,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,159\u003csup\u003eF\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration (days) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (8\u0026ndash;23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (6\u0026ndash;29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,969\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECMO\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (18,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,712\u003csup\u003eF\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration (days) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7,5 (2\u0026ndash;16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (6\u0026ndash;54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,476\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCRRT\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (81,3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (46,9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,021\u003c/b\u003e\u003csup\u003e\u003cb\u003eC\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration (days) \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (10\u0026ndash;30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (10\u0026ndash;31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,821\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlasma exchange\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (31,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (34,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1,0\u003csup\u003eC\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoadsorption \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,037\u003c/b\u003e\u003csup\u003e\u003cb\u003eF\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIM2 upon entering PICU\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (10,1\u0026ndash;64,8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4,6 (2,1\u0026ndash;13,6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,010\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRelapse of disease \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6,3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (34,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,040\u003csup\u003eC\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays in PICU\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27 (16\u0026ndash;37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (9\u0026ndash;36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,308\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePICU stay\u0026thinsp;\u0026gt;\u0026thinsp;28 days \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (34,4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,307\u003csup\u003eC\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e1\u003c/sup\u003eNumber (%) - Chi-square test C/ Fisher exact test F; \u003csup\u003e2\u003c/sup\u003eMedian (1st-3rd quartile) - Mann-Whitney test.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMortality was higher among primary HLH (60%) and onco-hematological cases (100%). Secondary HLH cases showed a mortality rate of 35.1%, while MAS cases had no observed mortality (0%) in this study sample. MAS also exhibited a higher relapse rate (66.7%) compared to pHLH (20%) and sHLH (18.9%).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eTo the best of our knowledge, our study reports on the characteristics of one of the largest pediatric series of patients with pHLH and sHLH treated in the PICU setting. In our cohort, the distribution between males and females (22 vs. 26, respectively) was similar. We found that primary HLH forms tend to have an earlier onset in childhood, and among the secondary forms, infectious predisposition was the most common (48.8%).\u003c/p\u003e\u003cp\u003eA previous study [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] reported an overall survival rate of 45%, with increased mortality associated with HLH triggered by infection or malignancy. However, differences in survival did not correlate with genetic profile or the extent of therapy. The same study [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] discusses how the uncertain performance of the HLH-2004 criteria and the consequences of missed or incorrect diagnoses have led to widely variable approaches to diagnosis and treatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These findings are consistent with our sample, where overall mortality in the PICU was high (33.3%), particularly in the primary HLH group (60%) and the onco-hematological group (100%), but no mortality was observed among the MAS group (0%).\u003c/p\u003e\u003cp\u003eIn our cohort, patients with the worst prognosis exhibited features such as splenomegaly at onset, lower platelet counts, and higher ferritin levels at PICU admission. Extracorporeal support therapies were used uniformly across all patients, but for longer durations in the most severe cases, which correlated with higher mortality.\u003c/p\u003e\u003cp\u003eThe higher mortality observed in primary HLH and sHLH related to onco-hematological disease may be linked to underlying genetic conditions that predispose these patients to early childhood risks, as well as to compromised general health and comorbidities in the latter group. Conversely, the more frequent relapses seen in the MAS group, with no associated mortality, likely reflect the classic pattern of recurrent exacerbations of rheumatological disorders. Early diagnosis and targeted therapies in patients with known diagnoses may also contribute to this trend.\u003c/p\u003e\u003cp\u003eIn our population, pHLH always presented with a full symptom complex. Fever was the most common clinical symptom, even in secondary forms. Splenomegaly and bone marrow hemophagocytosis were frequent but not universal. According to the literature [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], splenomegaly occurs in about 79% of HLH cases (survivors 84.85%, non-survivors 66.67%), likely due to immune activation, especially of lymphocytes and macrophages. In our study, splenomegaly at onset was more common in patients who died compared to those who survived (overall 58.3%, survivors 53.1%, non-survivors 68.8%). This suggests that more severe immune activation may lead to a more severe clinical presentation, with splenomegaly potentially serving as a negative prognostic factor.\u003c/p\u003e\u003cp\u003eThe incidence of multi-organ failure (MOF), central nervous system impairments, and renal dysfunction was higher among non-survivors, though these differences did not reach statistical significance.\u003c/p\u003e\u003cp\u003eThe length of PICU stay was shorter in the MAS group and longer in the other groups. The hepatobiliary damage (HBD) score changed from T1 to T2, worsening in the pHLH group (which showed no alterations at T1), improving among MAS patients, and worsening in other sHLH cases\u0026mdash;indicating a greater involvement of the hepatobiliary system in secondary non-rheumatologic forms of HLH. The Pediatric Index of Mortality 2 (PIM2) at T1 was higher in pHLH (19.6%), lower in sHLH (8.2%), and much lower in MAS (2.1%). PIM2 was also significantly higher among non-survivors (25% vs. 4.6%; p\u0026thinsp;=\u0026thinsp;0.01; see Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). This finding suggests that PIM2 could serve as a reliable prognostic tool.\u003c/p\u003e\u003cp\u003eFerritin levels at T1 were similar across pHLH, sHLH, and MAS; however, at T2, ferritin levels were higher in pHLH, lower in MAS, and much lower in other sHLH cases. Ferritin levels were approximately three times higher among non-survivors compared to survivors at T1 (p\u0026thinsp;=\u0026thinsp;0.069) and about twice as high at T2 (p\u0026thinsp;=\u0026thinsp;0.01), confirming that ferritin functions as a prognostic biomarker in HLH [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRegarding white blood cell counts, we observed differences among MAS, sHLH, and pHLH, but values remained within the normal range for both survivors and non-survivors. Therefore, white blood cell count does not appear to be useful for predicting severity.\u003c/p\u003e\u003cp\u003eIn contrast, platelet counts were lower among non-survivors at both T1 and T2, indicating that this parameter could help identify patients at higher risk of death. This trend of decreasing platelets and white blood cells may reflect a better disease status at T1 in some patients, while the uniformity of worse values at T2 across groups likely indicates clinical worsening.\u003c/p\u003e\u003cp\u003eLDH levels were elevated in all groups. In pHLH patients, LDH increased from three times the upper normal limit at T1 to twenty times at T2. In MAS patients, LDH remained consistently high (about 17 times the normal), while in sHLH patients, it increased from 5 to 8 times from T1 to T2.\u003c/p\u003e\u003cp\u003eExtracorporeal support techniques played a significant role in our patient management, especially considering that this study was conducted in the PICU setting, where all patients had severe HLH, rapidly evolving clinical conditions, or hemodynamic instability. Patients with more severe conditions required extracorporeal support more frequently and for longer durations. Often, a combination of techniques was used (e.g., invasive mechanical ventilation, CRRT, ECMO, plasma exchange, hemoadsorption).\u003c/p\u003e\u003cp\u003eAll patients with pHLH initially received non-invasive ventilation, and most patients with pHLH, MAS, and sHLH also required invasive mechanical ventilation. Interestingly, long-term mechanical ventilation (more than 14 days) was associated with survival in our cohort. ECMO was used only in the sHLH group (a total of 10 patients, with only one patient having MAS), with a median duration of 7 days. ECMO was applied at similar rates among survivors (18.8%) and non-survivors (25%), with the same median duration (7 vs. 7.5 days). However, the mean duration was about three times longer in non-survivors (10.5 vs. 33.3 days).\u003c/p\u003e\u003cp\u003eRenal replacement therapy (CRRT) was more frequently required in non-survivors (81.3%) compared to survivors (46.9%), and for longer periods (20 vs. 16 days). Plasma exchange was performed only in MAS and sHLH groups, at similar rates among survivors (34.4%) and non-survivors (31.3%). Hemoadsorption with CytoSorb was used in one case of pHLH and in four cases of sHLH, mainly among non-survivors (6.3% vs. 25%).\u003c/p\u003e\u003cp\u003eThe high incidence of extracorporeal therapies and mechanical ventilation in our cohort of critically ill children admitted to the PICU reflects the complexity of these patients and the high prevalence of organ dysfunction associated with HLH as a hyperinflammatory syndrome.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eHemophagocytic lymphohistiocytosis (HLH) is associated with high mortality despite intensive care and maximal therapeutic support. Mortality is particularly elevated in patients with primary HLH and those with onco-hematological forms. While MAS patients were prone to relapse, no deaths occurred in this subgroup during the study period. Early presence of splenomegaly, low platelet count, and elevated ferritin levels at PICU admission are potential predictors of adverse outcomes. The PIM2 score may serve as a useful prognostic tool in HLH. Extracorporeal support therapies\u0026mdash;including ECMO, invasive mechanical ventilation, continuous renal replacement therapy (CRRT), plasma exchange, and CytoSorb\u0026mdash;were applied consistently across patients, though for longer durations in the most severe cases, which correlated with higher mortality. To our knowledge, this is one of the largest pediatric cohorts of patients with both primary and secondary HLH treated in a PICU setting.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCMV: cytomegalovirus\u003c/p\u003e\n\u003cp\u003eCRRT: Continuous Renal Replacement Therapy\u003c/p\u003e\n\u003cp\u003eDIC: diffuse intravascular coagulation\u003c/p\u003e\n\u003cp\u003eEBV: Epstein-Barr virus\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eECMO: extracorporeal membrane oxygenation\u003c/p\u003e\n\u003cp\u003eHBD: hepatobiliary damage\u003c/p\u003e\n\u003cp\u003eHLH: hemophagocytic lymphohistiocytosis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMAS: macrophage activation syndrome\u003c/p\u003e\n\u003cp\u003eMOF: multiple organ failure\u003c/p\u003e\n\u003cp\u003eMV: mechanical ventilation\u003c/p\u003e\n\u003cp\u003epHLH: primary hemophagocytic lymphohistiocytosis\u003c/p\u003e\n\u003cp\u003ePICU: pediatric intensive care unit\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePIM2: Pediatric Index of Mortality\u003c/p\u003e\n\u003cp\u003esHLH: secondary hemophagocytic lymphohistiocytosis\u003c/p\u003e\n\u003cp\u003esJIA: systemic juvenile idiopathic arthritis\u003c/p\u003e\n\u003cp\u003eSLE: systemic lupus erythematosus\u003c/p\u003e\n\u003cp\u003eSPENCD: Spondyloenchondrodysplasia\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study received approval from the Institutional Review Board of Children Hospital Bambino Ges\u0026ugrave;. Informed consent was waived due to the retrospective nature of the study. This study was performed in line with the principles of the Declaration of Helsinki. This is an observational study. Approval was granted by the Ethics Committee of Bambino Ges\u0026ugrave; Children\u0026apos;s Hospital, IRCCS, Rome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eAll phases of this study were supported by Bambino Ges\u0026ugrave; Children\u0026rsquo;s Hospital, IRCCS, Rome, Italy. This work was supported by the Italian Ministry of Health with Current Research funds.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eMM, GB, CB and MDN conceptualized and designed the study, coordinate and supervised collected data and drafted the initial manuscript; FC, FDL, PM conceptualized and designed the study, coordinate and supervised collected data, and drafted the initial manuscript; DPM, collaborate to the design of the study and performed all statistical analyses, contributed to manuscript drafting, critically reviewed and revised the manuscript; \u0026nbsp;MM, GB, CB, MDN, FC, FDL and PM collaborate to the design of the study, contributed to manuscript drafting, critically reviewed and revised the manuscript; CC and FDB designed the study, \u0026nbsp;supervised data collection, and reviewed and revised the manuscript for important intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJoseph A, Carcillo B, Shakoory D, Simon. Kate Kernan. Understanding Disseminated Intravascular Coagulation and Hepatobiliary Dysfunction Multiple Organ Failure in Hyperferritinemic Critical Illness. Pediatric Critical Care Medicine, October 2018 \u0026bull; Volume 19 \u0026bull; Number 10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/PCC.0000000000001712\u003c/span\u003e\u003cspan address=\"10.1097/PCC.0000000000001712\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRavelli A, Grom AA, Behrens EM, Cron RQ. Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment. Genes Immun. 2012;13:289\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJanka G, Imashuku S, Elinder G, Schneider M, Henter JI. Infection and malignancy associated hemophagocytic syndromes. Secondary hemophagocytic lymphohistiocytosis. Hematol Oncol Clin North Am. 1998;12:435\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCastillo L, Carcillo J. Secondary hemophagocytic lymphohistiocytosis and severe sepsis/ systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation. Pediatr Crit Care Med. 2009;10(3):387\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/PCC.0b013e3181a1ae08\u003c/span\u003e\u003cspan address=\"10.1097/PCC.0b013e3181a1ae08\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID:19325510.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJanka GE. Familial hemophagocytic lymphohistiocytosis., Eur JP. 1983 Jun-Jul;140(3):221\u0026thinsp;\u0026ndash;\u0026thinsp;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF00443367\u003c/span\u003e\u003cspan address=\"10.1007/BF00443367\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 6354720.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJanka GE. Hemophagocytic syndromes. Blood Rev. 2007;21:245\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLarroche C, Mouthon L. Pathogenesis of hemophagocytic syndrome (HPS). Autoimmun Rev. 2004;3:69\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGrom A, Horne A AC and, De Benedetti F. Macrophage activation syndrome in the era of biologic therapy. Nat Reviews Rheumatol volume. 2016;12:pages259\u0026ndash;268.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBracaglia C, Prencipe G, De Benedetti F, Bracaglia, et al. Pediatr Rheumatol. 2017;15:5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12969-016-0130-4\u003c/span\u003e\u003cspan address=\"10.1186/s12969-016-0130-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIshii E, Ohga S, Imashuku S, et al. Review of hemophagocytic lymphohistiocytosis (HLH) in children with focus on Japanese experiences. Crit Rev Oncol Hematol. 2005;53:209\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarcenaro S, Gallo F, Martini S, et al. Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease. Blood. 2006;108:2316\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJoseph A, Carcillo B, Shakoory D, Simon. Kate Kernan. Understanding Disseminated Intravascular Coagulation and Hepatobiliary Dysfunction Multiple Organ Failure in Hyperferritinemic Critical Illness. Pediatric Critical Care Medicine, October 2018 \u0026bull; Volume 19 \u0026bull; Number 10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/PCC.0000000000001712\u003c/span\u003e\u003cspan address=\"10.1097/PCC.0000000000001712\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoldman J, Desai MS, McClain KL, et al. Hepatobiliary Dysfunction and Disseminated Intravascular Coagulation Increase Risk of Mortality in Pediatric Hemophagocytic Lymphohistiocytosis. Ped Crit Care Med. 2018;19:e522\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKyriazopoulou E, Leventogiannis K, Norrby-Teglund A, Hellenic Sepsis Study Group, et al. Macrophage activation-like syndrome: An immunological entity associated with rapid progression to death in sepsis. BMC Med. 2017;15:172.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMachowicz R, Jankab G, Wiktor-Jedrzejczak W. Similar but not the same: Differential diagnosis of HLH and sepsis. Crit Rev Oncol/Hematol. 2017;114:1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHenter JI, Horne A, Aric\u0026oacute; M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124\u0026thinsp;\u0026ndash;\u0026thinsp;31. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/pbc.21039\u003c/span\u003e\u003cspan address=\"10.1002/pbc.21039\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 16937360.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRavelli A, Minoia F, Dav\u0026igrave; S, Horne A, Bovis F, Pistorio A, Aric\u0026ograve; M, Avcin T, Behrens EM, De Benedetti F, Filipovic L, Grom AA, Henter JI, Ilowite NT, Jordan MB, Khubchandani R, Kitoh T, Lehmberg K, Lovell DJ, Miettunen P, Nichols KE, Ozen S, Pachlopnik Schmid J, Ramanan AV, Russo R, Schneider R, Sterba G, Uziel Y, Wallace C, Wouters C, Wulffraat N, Demirkaya E, Brunner HI, Martini A, Ruperto N, Cron RQ. Paediatric Rheumatology International Trials Organisation; Childhood Arthritis and Rheumatology Research Alliance; Pediatric Rheumatology Collaborative Study Group; Histiocyte Society. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol. 2016;68(3):566\u0026ndash;76. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/art.39332\u003c/span\u003e\u003cspan address=\"10.1002/art.39332\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2016 Feb 9. PMID: 26314788.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoldman J, Desai MS, McClain KL, Tcharmtchi MH, Kennedy CE, Thompson K, Lam F, Bashir DA, Chinn IK, Goldberg BR, Allen CE, Nguyen TC. Hepatobiliary Dysfunction and Disseminated Intravascular Coagulation Increase Risk of Mortality in Pediatric Hemophagocytic Lymphohistiocytosis. Pediatr Crit Care Med. 2018;19(10):e522\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/PCC.0000000000001684\u003c/span\u003e\u003cspan address=\"10.1097/PCC.0000000000001684\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 30113519; PMCID: PMC9097722.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChinn IK, Eckstein OS, Peckham-Gregory EC, Goldberg BR, Forbes LR, Nicholas SK, Mace EM, Vogel TP, Abhyankar HA, Diaz MI, Heslop HE, Krance RA, Martinez CA, Nguyen TC, Bashir DA, Goldman JR, Stray-Pedersen A, Pedroza LA, Poli MC, Aldave-Becerra JC, McGhee SA, Al-Herz W, Chamdin A, Coban-Akdemir ZH, Jhangiani SN, Muzny DM, Cao TN, Hong DN, Gibbs RA, Lupski JR, Orange JS, McClain KL, Allen CE. Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis. Blood. 2018;132(1):89\u0026ndash;100. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/blood-2017-11-814244\u003c/span\u003e\u003cspan address=\"10.1182/blood-2017-11-814244\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2018 Apr 9. PMID: 29632024; PMCID: PMC6034641.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118(15):4041-52. doi: 10.1182/blood-2011-03-278127. Epub 2011 Aug 9. PMID: 21828139; PMCID: PMC3204727.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHenter JI, Elinder G. Familial hemophagocytic lymphohistiocytosis. Clinical review based on the findings in seven children. Acta Paediatr Scand. 1991;80(3):269\u0026thinsp;\u0026ndash;\u0026thinsp;77. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1651-2227.1991.tb11849.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1651-2227.1991.tb11849.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 2035321.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eImashuku S, Kuriyama K, Teramura T, Ishii E, Kinugawa N, Kato M, Sako M, Hibi S. Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J Clin Oncol. 2001;19(10):2665-73. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/JCO.2001.19.10.2665\u003c/span\u003e\u003cspan address=\"10.1200/JCO.2001.19.10.2665\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 11352958.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYu TY, Lu MY, Lin KH, Chang HH, Chou SW, Lin DT, Jou ST, Yang YL. Outcomes and prognostic factors associated with 180-day mortality in Taiwanese pediatric patients with Hemophagocytic Lymphohistiocytosis. J Formos Med Assoc. 2021;120(4):1061\u0026ndash;8. Epub 2020 Nov 17. PMID: 33218852.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"proj","sideBox":"Learn more about [Pediatric Rheumatology](http://ped-rheum.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/proj/default.aspx","title":"Pediatric Rheumatology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"hemophagocytic lymphohistiocytosis, HLH, macrophage activation syndrome, MAS, pediatric intensive care, PICU, extracorporeal support, organ failure, mortality, inflammation","lastPublishedDoi":"10.21203/rs.3.rs-8216536/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8216536/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eHemophagocytic lymphohistiocytosis (HLH) is a challenging and potentially life-threatening condition characterized by an uncontrolled inflammatory response resulting from hyperactivation of T lymphocytes and macrophages, leading to excessive production of inflammatory cytokines. HLH can lead to multiple organ failure and death in a significant proportion of cases. It is challenging to differentiate HLH from sepsis. This study aims to describe the clinical characteristics, risk factors, and outcomes of a cohort of children admitted to a pediatric intensive care unit (PICU) with primary and secondary hemophagocytic lymphohistiocytosis (pHLH and sHLH).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eRetrospective observational analysis of all children with HLH admitted to the PICU between 2006 and 2019.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Patients were evaluated at two time points: upon PICU admission (T1) and at the time of the highest ferritin level (T2). A total of 48 patients were included: 5 with pHLH, 37 with sHLH, and 6 with macrophage activation syndrome (MAS) in the context of systemic juvenile idiopathic arthritis (sJIA). The overall mortality rate in the PICU was 33.3%. Mortality rates within each group were: 60% for pHLH, 35.1% for sHLH, and nobody for MAS. The Pediatric Index of Mortality (PIM2) was higher among non-survivors. Splenomegaly and leukopenia at PICU admission were more common in non-survivors compared to survivors, as were the incidence of multiple organ failure and acute renal failure during the PICU stay. Platelet counts were significantly lower in patients who died, but only at T2. Ferritin levels remained consistently elevated in non-survivors throughout their PICU stay.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eIn this cohort, mortality among children admitted to the PICU with HLH was high, particularly among those with primary or onco-hematological forms. Conversely, patients with MAS experienced more relapses but no mortality was observed in this sample. Early presence of splenomegaly, low platelet count, elevated ferritin levels, and PIM2 score at PICU admission appear to be indicators of poor prognosis. These findings may help to early identify patients at highest risk for complications and mortality.\u003c/p\u003e","manuscriptTitle":"Critical care outcomes of hemophagocytic lymphohistiocytosis in children: a single centre retrospective observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-04 12:06:54","doi":"10.21203/rs.3.rs-8216536/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-19T02:37:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-16T01:42:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-08T06:35:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190414550382783653346214344353562150152","date":"2025-12-02T23:28:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"46711468913491638154300742206055818228","date":"2025-12-02T21:49:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-02T20:25:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-02T12:22:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-02T12:20:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Rheumatology","date":"2025-11-26T23:34:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"proj","sideBox":"Learn more about [Pediatric Rheumatology](http://ped-rheum.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/proj/default.aspx","title":"Pediatric Rheumatology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6c707385-047c-428d-b1ca-d05867bdfdde","owner":[],"postedDate":"December 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-03-31T20:38:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-04 12:06:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8216536","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8216536","identity":"rs-8216536","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}