Clinical Profile and Outcomes of Thrombotic Microangiopathy - A Prospective Study From a Tertiary Centre in India

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While thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) dominate Western cohorts, secondary TMAs due to snake envenomation and sepsis are increasingly recognized in tropical regions. We conducted a prospective study to evaluate the clinical spectrum, laboratory features, risk stratification, treatment, and outcomes of TMA in an Indian tertiary care setting. Methods Consecutive patients with newly diagnosed TMA were enrolled between March 2024 and April 2025. Patients were categorized as TTP, HUS, or secondary TMA. Demographic, clinical, and laboratory data were recorded. PLASMIC scores were calculated, and ADAMTS13 activity was assessed where feasible. Treatment strategies, including plasma exchange, dialysis, antisnake venom, and supportive care, were documented. The primary outcome was discharge status (recovered vs. died). Results Sixty-six patients were included: TTP (n = 16), HUS (n = 34), and secondary TMA (n = 16). Patients with TTP were older and more likely to present with neurologic symptoms, whereas HUS demonstrated the highest renal burden and dialysis requirement. Secondary TMAs were predominantly due to snakebite (n = 20) and sepsis (n = 17). Hemoglobin was lowest in secondary TMA, creatinine was highest in HUS, and LDH was elevated across all subtypes. The PLASMIC score effectively stratified TTP, with severe ADAMTS13 deficiency confirmed in most tested cases. Plasma exchange was performed in 14 patients (mainly TTP), while all snakebite cases received antisnake venom, 4 patients received plasma exchange. Overall survival was 71.2%: HUS 82.4%, TTP 62.5%, and secondary TMA 56.2%. Mortality was highest in sepsis-associated TMA. Conclusion In this prospective Indian cohort, TMA presented with distinct subtype-specific patterns. The PLASMIC score enabled early recognition of TTP, while snakebite- and sepsis-associated TMAs contributed substantially to disease burden and outcomes. These findings highlight the need for context-specific strategies for TMA management in tropical settings. Thrombotic microangiopathy (TMA) Thrombotic thrombocytopenic purpura (TTP) Hemolytic uremic syndrome (HUS) PLASMIC score ADAMTS13 Snakebite Sepsis India Plasma Exchange Introduction Thrombotic microangiopathies (TMAs) are rare but severe syndromes characterized by microangiopathic hemolytic anemia, thrombocytopenia, and variable organ dysfunction caused by widespread microvascular thrombosis [ 1 , 2 ]. The principal primary forms are thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), while secondary TMAs occur in association with diverse triggers including infection, autoimmune disease, pregnancy, malignancy, drugs, and envenomation [ 3 – 6 ]. TTP, first described by Moschcowitz in 1924, was historically almost uniformly fatal until the advent of plasma exchange, which remains the cornerstone of therapy [ 5 , 16 ]. Its pathogenesis was clarified with the recognition that severe deficiency of ADAMTS13, a von Willebrand factor–cleaving protease, underlies most cases, due to either autoantibodies or inherited mutations [ 7 , 18 , 27 , 47 ]. Registry data have demonstrated that rapid recognition and plasma exchange dramatically reduce mortality, bringing survival rates closer to those reported in Western cohorts [ 8 , 9 ]. In contrast, HUS was classically linked to Shiga toxin–producing Escherichia coli and presents with predominant renal injury [ 6 , 13 ]. Later, atypical HUS (aHUS) was identified as a complement-mediated disorder with poor renal prognosis if untreated, but dramatically altered outcomes with complement inhibitors such as eculizumab [ 14 , 45 ]. This evolution highlights the importance of molecular classification for prognosis and therapy. Secondary TMAs account for a substantial proportion of cases globally and are particularly common in low- and middle-income countries. Sepsis, autoimmune disorders, malignant hypertension, transplantation, and snake envenomation are recognized precipitants [ 19 , 20 , 34 , 35 , 43 ]. In contrast to registries from Europe and North America—where malignancy, drugs, and transplantation predominate [ 19 , 41 , 44 , 46 ]—Indian and tropical cohorts report a significant burden of snakebite- and infection-related TMA [ 35 – 38 , 40 ]. These conditions share overlapping mechanisms of endothelial injury, complement activation, and coagulation abnormalities, complicating diagnosis and management [ 21 – 23 ]. Despite advances, TMAs remain diagnostically and therapeutically challenging. Geographic variation is striking: primary TTP and complement-mediated HUS dominate in Western series [ 8 , 41 ], whereas secondary TMAs due to sepsis and snake envenomation contribute substantially in tropical countries [ 34 – 38 ]. Systematic evaluation of clinical spectrum, management, and outcomes in such contexts is essential to refine diagnostic strategies and improve survival. We therefore conducted a prospective observational study at a tertiary center in southern India to describe the profile, treatment, and short-term outcomes of TMA, with emphasis on the role of the PLASMIC score and the contribution of secondary TMAs to disease spectrum. Materials and Methods Study design and setting We conducted a prospective observational study at Kasturba Medical College, Manipal, between March 2024 and April 2025. Consecutive patients presenting with clinical and laboratory features suggestive of thrombotic microangiopathy (TMA) were enrolled. Ethical approval was obtained from the Institutional Ethics Committee, and written informed consent was obtained from all participants. Inclusion and exclusion criteria Eligible patients were those with newly diagnosed TMA, defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and at least one organ involvement. Patients with pregnancy-associated TMA (preeclampsia, HELLP syndrome, or pregnancy-triggered atypical HUS) were excluded, as these syndromes represent distinct entities with unique pathophysiology and maternal–fetal outcomes. Data collection At baseline, demographic details, comorbidities, and clinical presentations were recorded. Laboratory parameters included hemoglobin, platelet count, lactate dehydrogenase (LDH), serum creatinine, coagulation profile, and fibrinogen. Schistocyte grading was performed on peripheral blood smears. The PLASMIC score [ 10 ] was calculated to assess the likelihood of severe ADAMTS13 deficiency. ADAMTS13 activity and Complement assays (C3, C4) were performed when a strong clinical suspicion was present. Classification of subtypes Patients were categorized as: TTP : Microangiopathic hemolytic anemia with thrombocytopenia in the absence of an alternative cause; severe ADAMTS13 deficiency (< 10%) confirmed the diagnosis when tested. HUS : Renal-predominant microangiopathy without severe ADAMTS13 deficiency; no Shiga toxin–associated cases were identified. Where available, complement evaluation supported the diagnosis of atypical HUS or HUS of uncertain mechanism. Secondary TMA : A clear precipitating factor (e.g., sepsis, autoimmune disease, snake envenomation, malignancy, drug exposure) was present. In cases with overlapping triggers or incomplete testing, final classification was made by investigator consensus after review of all clinical, laboratory, and treatment data. Treatment modalities Treatment was individualized according to institutional protocol. Plasma exchange was considered for suspected TTP and selected severe secondary TMAs. Fresh frozen plasma was administered as adjunctive therapy. Hemodialysis was performed when clinically indicated for acute kidney injury. Antisnake venom was administered in all cases of envenomation. Rituximab was used in refractory or relapsing TTP. Supportive measures included transfusion of red blood cells, infection control, and organ support as appropriate. Outcome assessment Patients were followed throughout the index hospitalization. The primary outcome was discharge status (recovered vs. died). Secondary outcomes included the need for dialysis, renal function at discharge, and the occurrence of major in-hospital complications. Statistical analysis Data were analyzed using SPSS version XX (IBM, Armonk, NY) . Categorical variables were expressed as proportions and compared using the Chi-square or Fisher’s exact test. Continuous variables were summarized as mean ± SD or median (IQR) and compared using Student’s t -test or Mann–Whitney U test as appropriate. A p -value < 0.05 was considered statistically significant. Results Cohort and subtype distribution A total of 66 patients with thrombotic microangiopathy were enrolled, comprising 16 with thrombotic thrombocytopenic purpura (TTP, 24.2%), 34 with hemolytic uremic syndrome (HUS, 51.5%), and 16 with secondary TMA (24.2%). Within the secondary TMA group, the most frequent precipitants were snake envenomation (n = 20 overall) and sepsis (n = 15), followed by autoimmune diseases and malignant hypertension. Baseline characteristics (Table 1 ) The mean age was highest in patients with TTP (53.4 ± 16.6 years), followed by secondary TMA (47.7 ± 16.1 years) and HUS (43.8 ± 19.0 years), though these differences were not statistically significant (p = 0.174). Sex distribution was comparable across groups, with no significant difference in male-to-female ratios. Comorbidities were most frequent in TTP: hypertension was present in 37.5% and diabetes in 25%, compared with 11.8% and 17.6% respectively, in HUS, while secondary TMA had lower rates (12.5% and none, respectively). Chronic kidney disease and ischemic heart disease were rare overall, and no significant differences were observed between groups. Presenting complaints varied by subtype. Fever was common in TTP (68.8%) and HUS (61.8%), but less frequent in secondary TMA (31.2%). Edema was strikingly more common in HUS (58.8%, p = 0.0014). Abdominal distension occurred more often in TTP (25%). Neurologic manifestations were prominent in TTP and secondary TMA: altered sensorium was noted in 31.2% and 37.5% respectively, compared with only 11.8% in HUS. Seizures were documented in 12.5% of TTP and 6.2% of secondary TMA. Respiratory symptoms, such as breathlessness, occurred in one-third of TTP and secondary TMA patients, but only 11.8% of HUS. Gastrointestinal complaints, including vomiting (20–31%) and diarrhea (6–19%), occurred across groups without significant differences. Renal dysfunction was most pronounced in HUS, with decreased urine output reported in 29.4% of patients, compared with 12.5% in TTP and 6.2% in secondary TMA. Hematuria and jaundice were infrequent in all subtypes. Table 1 Baseline characteristics of patients with thrombotic microangiopathy (TMA) by subtype Characteristic TTP (n = 16) HUS (n = 34) Secondary TMA (n = 16) p-value Demographics Age, years (mean ± SD) 53.4 ± 16.6 43.8 ± 19.0 47.7 ± 16.1 0.1743 Male sex, n (%) 8 (50.0) 18 (52.9) 10 (62.5) 0.7494 Female sex, n (%) 8 (50.0) 16 (47.1) 6 (37.5) 0.7494 Comorbidities Hypertension, n (%) 6 (37.5) 4 (11.8) 2 (12.5) 0.0706 Type 2 diabetes, n (%) 4 (25.0) 6 (17.6) 0 (0.0) 0.1207 Chronic kidney disease, n (%) 0 (0.0) 0 (0.0) 1 (6.2) 0.2046 Ischemic heart disease, n (%) 1 (6.2) 0 (0.0) 0 (0.0) 0.2046 Bronchial asthma, n (%) 0 (0.0) 1 (2.9) 0 (0.0) 0.6201 Presenting features Fever, n (%) 11 (68.8) 21 (61.8) 5 (31.2) 0.0641 Breathlessness, n (%) 5 (31.2) 4 (11.8) 5 (31.2) 0.1537 Vomiting, n (%) 4 (25.0) 7 (20.6) 5 (31.2) 0.7118 Diarrhea, n (%) 1 (6.2) 4 (11.8) 3 (18.8) 0.5538 Altered sensorium, n (%) 5 (31.2) 4 (11.8) 6 (37.5) 0.0830 Seizures, n (%) 2 (12.5) 0 (0.0) 1 (6.2) 0.1314 Decreased urine output, n (%) 2 (12.5) 10 (29.4) 1 (6.2) 0.1118 Hematuria, n (%) 1 (6.2) 1 (2.9) 0 (0.0) 0.5870 Abdominal distension, n (%) 4 (25.0) 2 (5.9) 1 (6.2) 0.0994 Edema/Swelling, n (%) 2 (12.5) 20 (58.8) 3 (18.8) 0.0014 Laboratory parameters (Table 2 ; Supplementary Tables 1–3) Hematological profile Baseline hemoglobin was lowest in secondary TMA (8.1 ± 2.6 g/dL) compared with HUS (9.2 ± 2.0 g/dL) and TTP (10.9 ± 2.6 g/dL) (p = 0.017). Hemoglobin trends during hospitalization showed improvement across groups in patients who survived, though recovery was slower in HUS and secondary TMA. Platelet counts were uniformly depressed at baseline in all groups (mean 58–66 × 10³/µL). Gradual recovery was observed over the first week, with median counts approaching 90–145 × 10³/µL by day 9, particularly in HUS. Renal profile Renal dysfunction was most severe in HUS, with the highest admission creatinine (7.3 ± 4.5 mg/dL, median 5.6) compared with secondary TMA (5.4 ± 4.6 mg/dL, median 4.9) and TTP (3.2 ± 1.9 mg/dL, median 2.4) (p = 0.004). Serial measurements confirmed persistently higher creatinine and urea in HUS, reflecting its renal-predominant phenotype. Hemolysis markers LDH was elevated across all groups at baseline, with the highest mean in HUS (1521 IU/L), followed by secondary TMA (1269 IU/L) and TTP (917 IU/L). Levels declined progressively with treatment but remained above reference ranges through the first week. Indirect bilirubin was mildly elevated but did not differ significantly across groups. Coagulation profile INR values were largely preserved in TTP and HUS but showed more variability in secondary TMA. Fibrinogen levels were frequently depressed in sepsis-associated secondary TMA, with some patients reaching undetectable values, while TTP patients generally had higher levels. Table 2 Laboratory parameters Parameter TTP (n = 16) HUS (n = 34) Secondary TMA (n = 16) p-value Hematology Hemoglobin, g/dL 10.9 ± 2.6 9.2 ± 2.0 8.1 ± 2.6 0.018 Platelets, ×10³/µL 57.9 ± 48.2 58.5 ± 39.6 66.2 ± 48.2 0.797 Renal profile Serum creatinine, mg/dL 3.2 ± 1.9 7.3 ± 4.5 5.4 ± 4.6 0.004 Urea, mg/dL 94.5 ± 47.9 141.8 ± 66.8 138.9 ± 59.8 0.022 Hemolysis markers LDH, IU/L 917 ± 494 1521 ± 1065 1270 ± 1113 0.087 Coagulation Fibrinogen, mg/dL 196.5 ± 205.1 176.3 ± 128.7 228.4 ± 202.1 0.694 PLASMIC score and ADAMTS13 activity (Table 3 ) The PLASMIC score stratified patients in line with clinical diagnosis. High-probability scores (6–7) were observed in 87.5% of TTP cases, compared with 52.9% of HUS and only 18.8% of secondary TMA (p = 0.002). In contrast, low scores (≤ 4) clustered in secondary TMA (37.5%) and were absent in TTP. ADAMTS13 activity, available in 24 patients, confirmed severe deficiency (< 10%) in 75% of tested TTP cases, while none of the HUS or secondary TMA patients demonstrated this finding (p 50%) was typical in HUS and secondary TMA. These results validated the PLASMIC score as a bedside surrogate when ADAMTS13 testing was unavailable. Table 3 PLASMIC score distribution and ADAMTS13 activity Parameter TTP (n = 16) HUS (n = 34) Secondary TMA (n = 16) p-value PLASMIC score 0–4 (low probability) 0 (0.0%) 4 (11.8%) 6 (37.5%) < 0.001 5 (intermediate probability) 2 (12.5%) 12 (35.3%) 7 (43.8%) 0.041 6–7 (high probability) 14 (87.5%) 18 (52.9%) 3 (18.8%) < 0.001 Mean ± SD 6.5 ± 0.6 5.4 ± 1.1 4.7 ± 1.3 0.002 Median (IQR) 7 (6–7) 5 (5–6) 5 (4–6) 0.003 ADAMTS13 activity* < 10% (severe deficiency) 6/8 (75.0%) 0/10 (0.0%) 0/6 (0.0%) 50% 0/8 (0.0%) 8/10 (80.0%) 5/6 (83.3%) < 0.001 *ADAMTS13 activity was performed in a subset of 24 patients based on clinical suspicion. Treatments Plasma exchange was performed in 14 patients (21.2%), predominantly those with TTP, although it was also used in a minority of severe secondary TMA cases, including 4 with snakebite-related disease. Fresh frozen plasma was administered in 33 patients (50.0%). Hemodialysis was required in 41 patients (62.1%), mostly among HUS and secondary TMA. All patients with snakebite-associated TMA received antisnake venom. Rituximab was administered to 2 patients with refractory or relapsing TTP. Outcomes (Table 4 ) Overall in-hospital survival was 71.2% (47/66). Subtype-specific survival was highest in HUS (82.4%, 28/34), followed by TTP (62.5%, 10/16), and lowest in secondary TMA (56.2%, 9/16). Mortality was greatest in patients with sepsis-associated secondary TMA, where multiorgan failure was the predominant cause of death. Among patients with snakebite-related TMA (n = 20), most recovered with antisnake venom and supportive care; plasma exchange was selectively employed in 4 (20%), with good benefit. Table 4 OUTCOMES BY TMA SUBTYPE Outcome TTP (n = 16) HUS (n = 34) Secondary TMA (n = 16) Survival status Alive at discharge, n (%) 10 (62.5) 28 (82.4) 9 (56.2) Deaths, n (%) 6 (37.5) 6 (17.6) 7 (43.8) Discussion This prospective single-center study provides one of the few systematic characterizations of thrombotic microangiopathies (TMAs) from India, with particular emphasis on snakebite- and sepsis-associated disease. These secondary TMAs, seldom reported in Western cohorts, accounted for a substantial proportion of our cases and highlight the importance of region-specific data. While the clinical hallmarks of microangiopathic hemolytic anemia and thrombocytopenia were shared across subtypes, outcomes were strongly determined by the underlying etiology and the timeliness of intervention. Demographic and clinical profile Patients with thrombotic thrombocytopenic purpura (TTP) in our series were older (mean 53 years) and more likely to present with neurological features, consistent with reports from the International TTP Registry and the Oklahoma cohort [ 8 , 9 , 42 ]. Hemolytic uremic syndrome (HUS) demonstrated the greatest renal burden, with the highest creatinine and dialysis requirement, reflecting its renal-predominant phenotype and aligning with global descriptions of Shiga toxin–negative and complement-mediated HUS [ 13 , 14 , 26 , 45 ]. Secondary TMAs accounted for one-quarter of our patients, driven predominantly by snake envenomation and sepsis. This contrasts with European and North American registries where malignancy, transplantation, and drugs predominate [ 19 , 25 , 41 , 44 ]. Such differences emphasize the geographic variability in TMA epidemiology and the need for local cohort data. Laboratory features and risk stratification Hematologic indices at baseline reflected the systemic burden of microangiopathy. Anemia was universal but most pronounced in secondary TMAs, in keeping with prior reports that systemic inflammation and consumptive processes amplify hemolysis in infection- and malignancy-related disease [ 19 , 44 ]. TTP patients, in contrast, often maintained comparatively higher hemoglobin, similar to observations from the Oklahoma TTP Registry where anemia was less severe than in renal-predominant forms [ 9 , 42 ]. Platelet counts were profoundly reduced across all groups, but recovery patterns diverged: in our series, HUS patients demonstrated more rapid platelet recovery by day, while recovery in TTP and secondary TMAs was delayed. This echoes registry findings that hematologic remission is often achieved earlier in complement-mediated HUS than in antibody-mediated TTP, despite comparable initial thrombocytopenia [ 8 , 41 ]. Renal parameters clearly differentiated the subtypes. Patients with HUS showed the highest creatinine and urea levels throughout hospitalization, underscoring the renal-dominant phenotype described in classical and atypical HUS cohorts [ 13 , 14 , 45 ]. TTP patients generally exhibited only modest renal dysfunction, paralleling international registry data where neurologic rather than renal features predominated [ 8 , 42 ]. Secondary TMAs displayed intermediate renal involvement, consistent with heterogeneous etiologies ranging from sepsis to envenomation, which have been shown in prior Indian series to carry variable but often significant renal burden [ 35 – 38 ]. Markers of hemolysis were elevated across all groups, with LDH remaining above normal despite clinical improvement. Persistent LDH elevation despite hematologic recovery has been highlighted in both the French TMA Registry and the International TTP Registry as evidence of ongoing endothelial injury [ 19 , 41 ]. The highest levels were seen in HUS and secondary TMAs, consistent with more severe organ involvement. Indirect bilirubin showed only modest differences, echoing prior reports where LDH is the more sensitive marker of ongoing microangiopathy [ 21 , 22 ]. Coagulation profiles provided additional distinction. In TTP, INR and fibrinogen were generally preserved, in line with the absence of consumptive coagulopathy described in immune-mediated TTP [ 23 , 33 ]. By contrast, secondary TMAs—particularly those associated with sepsis—exhibited hypofibrinogenemia and variable INR elevation, reflecting overlap with disseminated intravascular coagulation [ 39 ]. This mirrors earlier descriptions by George et al. [ 22 ] and Levi et al. [ 23 ], where sepsis-associated TMA frequently displayed laboratory features intermediate between classical TMA and DIC. Risk stratification using the PLASMIC score aligned well with clinical phenotypes. High-probability scores clustered in TTP, enabling rapid recognition and initiation of plasma exchange even before ADAMTS13 confirmation. Similar utility of the PLASMIC score as an early surrogate for severe ADAMTS13 deficiency has been demonstrated in North American and European cohorts [ 10 – 12 ]. In the subset of patients tested, severe ADAMTS13 deficiency was confined to suspected TTP, validating both the score and the clinical classification. This concordance parallels findings from the International TTP Registry and other validation studies, underscoring the global relevance of bedside scoring even in resource-limited settings [ 8 , 11 , 48 ]. Treatment Therapy was tailored to subtype and resource availability. Plasma exchange was performed in 14 patients, predominantly with TTP, reaffirming its status as the standard of care [ 16 , 28 , 32 , 33 , 48 ]. Fresh frozen plasma was administered in half the cohort, largely as supportive therapy. Dialysis was required in over 60% of patients, particularly in HUS and secondary TMA, underscoring the renal burden. Rituximab was used in two patients with refractory TTP[ 17 ], but advanced therapies such as caplacizumab and eculizumab were unavailable, contrasting with contemporary Western practice [ 14 , 15 , 29 , 30 , 34 , 35 ]. This gap underscores the challenge of equitable access to novel agents in low- and middle-income countries. Snakebite-associated TMA is a distinctive strength of this study. All 20 patients received antisnake venom, with generally favorable short-term survival. Plasma exchange was selectively used in 20%, reflecting a pragmatic approach to refractory cases. Similar findings have been reported in recent Indian series: Sahay et al. (2018) described viper bite–related TMA requiring dialysis in most cases, with plasma exchange used selectively [ 36 ], while Patil et al. (2020) highlighted improved renal and hematologic recovery with early therapeutic plasma exchange [ 35 ]. More recently, Sukumar et al. (2020) emphasized the contribution of microangiopathy to snakebite-associated acute kidney injury and the role of supportive care including dialysis and plasma exchange in selected patients [ 37 ]. Our prospective data therefore complement these reports, supporting that plasma exchange is not universally required but may benefit patients with severe or refractory presentations[ 49 ]. Sepsis-associated TMA carried the highest mortality in our series. The overlap between endothelial injury, complement activation, and disseminated intravascular coagulation makes both diagnosis and management challenging. Recent work has emphasized that sepsis can trigger a TMA-like phenotype distinct from classical DIC. George (2020) described sepsis-associated TMA as an underrecognized entity requiring careful differentiation from DIC [ 22 ], while Levi et al. (2020) highlighted the complex interplay of coagulation and inflammation in septic microangiopathy [ 23 ]. These observations parallel our findings, where mortality was driven largely by multiorgan dysfunction despite supportive therapy. Prognosis and survival Overall in-hospital survival was 71.2%, comparable to international cohorts [ 8 , 41 ]. However, subtype-specific outcomes differed. Survival in TTP (62.5%) was lower than registry figures of ~ 80–90% [ 8 , 31 , 42 ], reflecting delayed recognition and limited access to caplacizumab or early rituximab. HUS survival (82.4%) was reasonable but lower than outcomes reported with eculizumab [ 14 , 45 ]. Secondary TMA had the poorest outcomes (56.2% survival), driven by sepsis-related mortality, in line with evidence that prognosis in secondary TMAs is dictated by the underlying trigger rather than the microangiopathy itself [ 19 , 22 , 44 ]. Snakebite-associated cases fared relatively better with antisnake venom and supportive care, highlighting an important distinction between tropical and Western etiologies [ 35 – 38 ]. Strengths and limitations Strengths of this study include its prospective design, systematic classification, and detailed evaluation of secondary TMAs relevant to tropical countries. Limitations include modest sample size, single-center setting, lack of long-term renal follow-up, and restricted access to molecular diagnostics. The absence of novel agents such as eculizumab and caplacizumab limited comparisons with outcomes in high-income settings. Conclusions Outcomes in TMA were determined more by underlying etiology and timeliness of therapy than by any single laboratory marker. The PLASMIC score proved highly effective for bedside risk stratification and guided early plasma exchange in suspected TTP. HUS carried the greatest renal burden, requiring intensive dialysis support, while secondary TMAs were dominated by snakebite and sepsis, reflecting the regional epidemiology. Snakebite-associated cases generally responded well to antisnake venom and supportive care, whereas sepsis-associated TMA had the highest mortality. These findings highlight the importance of early recognition, rapid initiation of plasma exchange in TTP, and context-specific strategies to address the burden of secondary TMAs in low- and middle-income countries. Declarations Ethics Approval and Consent to Participate The study was approved by the Institutional Ethics Committee, Kasturba Medical College, Manipal (IEC 2:648/2023). The study was conducted in accordance with the Declaration of Helsinki and its later amendments. Written informed consent was obtained from all participants. Conflict of Interest Statement The authors declare that they have no competing financial or personal interests that could have influenced the work reported in this manuscript. Funding Statement No external funding was received for this study. Author Contribution Dr Jagadeesh Mullapudi conceived and designed the study, collected and analyzed data, and drafted the manuscript. Dr Ram Bhat supervised the study and critically reviewed the manuscript.All authors approved the final version. Data Availability Data supporting the findings of this study are available from the corresponding author upon reasonable request. References George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014;371(7):654–66. doi: 10.1056/NEJMra1312353 Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836–46. doi: 10.1182/blood-2016-10-709857 Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of TTP. 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J Nephrol. 2019;32(4):517–30. doi: 10.1007/s40620-019-00577-6 Zheng XL. ADAMTS13 testing—methods and interpretation. Am J Hematol. 2015;90(12):1222–31. doi: 10.1002/ajh.24201 Sarode R, et al. ASFA guidelines on therapeutic plasma exchange. J Clin Apher. 2019;34(3):171–354. doi: 10.1002/jca.21705 Peyvandi F, et al. Caplacizumab phase 3 trial. N Engl J Med. 2016;374(6):511–22. doi: 10.1056/NEJMoa1505533 Page EE, et al. Rituximab to prevent relapses in TTP. Blood. 2016;127(24):3097–101. doi: 10.1182/blood-2016-02-697425 Scully M, et al. Long-term follow-up of TTP survivors. Blood. 2015;125(23):3828–36. doi: 10.1182/blood-2015-02-631275 Coppo P, et al. Early PEX and steroids in TTP. Haematologica. 2011;96(3):455–63. doi: 10.3324/haematol.2010.031401 Favaloro EJ, et al. Differentiating TTP from DIC and other TMAs. Pathology. 2017;49(7):713–29. doi: 10.1016/j.pathol.2017.08.007 Warrell DA. Snake bite. Lancet. 2010;375(9708):77–88. doi: 10.1016/S0140-6736(09)61754-2 Patil R, et al. Therapeutic plasma exchange in snakebite-induced TMA. Indian J Nephrol. 2020;30(2):97–103. doi: 10.4103/ijn.IJN_46_19 Sahay M, et al. TMA following viper envenomation. Nephrology (Carlton). 2018;23(3):262–8. doi: 10.1111/nep.13012 Sukumar S, et al. Snakebite-associated AKI in India. Clin Kidney J. 2020;13(3):351–7. doi: 10.1093/ckj/sfz114 Chugh KS, et al. Snakebite-induced acute kidney injury: Indian experience. Kidney Int. 1989;35(3):891–5. doi: 10.1038/ki.1989.77 Maduwage K, Isbister GK. Venom-induced consumption coagulopathy vs DIC. Thromb Res. 2014;133(3):539–46. doi: 10.1016/j.thromres.2014.01.015 Alirol E, et al. Snake bite envenoming: a neglected tropical disease. Lancet. 2015;386(10010):87–99. doi: 10.1016/S0140-6736(14)61686-9 Picod A, et al. French Reference Center for TMA: national cohort. Haematologica. 2019;104(12):2308–17. doi: 10.3324/haematol.2018.213686 Terrell DR, Williams LA, Okhuysen-Cawley R, et al. Oklahoma TTP-HUS Registry update. Am J Hematol. 2015;90(12):1254–60. doi: 10.1002/ajh.24214 Benhamou Y, et al. Cardiac involvement in TTP. Circulation. 2015;131(7):640–8. doi: 10.1161/CIRCULATIONAHA.114.013441 Mariotte E, et al. Cancer-associated TMAs. Oncologist. 2012;17(8):954–62. doi: 10.1634/theoncologist.2011-0464 Loirat C, Fakhouri F, Ariceta G, et al. Atypical HUS in children: recommendations. Pediatr Nephrol. 2016;31(1):15–39. doi: 10.1007/s00467-015-3076-8 Kremer Hovinga JA, Coppo P, et al. EULAR/ISTH/SSC consensus on TTP. J Thromb Haemost. 2021;19(6):1585–96. doi: 10.1111/jth.15320 Sadler JE. TTP and ADAMTS13: a mechanistic review. Annu Rev Pathol. 2015;10:395–415. doi: 10.1146/annurev-pathol-012414-040424 Kremer Hovinga JA, et al. Monitoring ADAMTS13 in TTP. Haematologica. 2022;107(11):2471–81. doi: 10.3324/haematol.2021.279959 Gupta A, et al. Thrombotic microangiopathy following snakebite: diagnostic challenges and outcomes. Indian J Nephrol. 2024;34(2):145–52. doi: 10.4103/ijn.ijn_2024_18 Additional Declarations No competing interests reported. Supplementary Files SupplementaryTables.docx Cite Share Download PDF Status: Posted Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7744574","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":535350417,"identity":"300c3e13-4e2d-4a97-aea0-5d4809fdeb63","order_by":0,"name":"Jagadeesh Mullapudi¹","email":"data:image/png;base64,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","orcid":"","institution":"Kasturba Medical College, Manipal","correspondingAuthor":true,"prefix":"","firstName":"Jagadeesh","middleName":"","lastName":"Mullapudi¹","suffix":""},{"id":535350419,"identity":"59f4dca3-6009-4e7a-87ed-35b0a7682b25","order_by":1,"name":"Ram 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07:09:07","extension":"html","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":118313,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7744574/v1/5b6df4b0c3ec0d13274d435d.html"},{"id":95226177,"identity":"960b4628-1386-43fb-a8fc-18add6a1977f","added_by":"auto","created_at":"2025-11-05 16:30:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1025722,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7744574/v1/caa397b4-b084-407b-99ae-059f781ef378.pdf"},{"id":94731990,"identity":"da14d03e-cc66-4f05-9811-3fb4c15f9946","added_by":"auto","created_at":"2025-10-30 07:09:03","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":19144,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7744574/v1/2079c2c5f0b9b74f530a4dd7.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eClinical Profile and Outcomes of Thrombotic Microangiopathy - A Prospective Study From a Tertiary Centre in India\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThrombotic microangiopathies (TMAs) are rare but severe syndromes characterized by microangiopathic hemolytic anemia, thrombocytopenia, and variable organ dysfunction caused by widespread microvascular thrombosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The principal primary forms are thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), while secondary TMAs occur in association with diverse triggers including infection, autoimmune disease, pregnancy, malignancy, drugs, and envenomation [\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTTP, first described by Moschcowitz in 1924, was historically almost uniformly fatal until the advent of plasma exchange, which remains the cornerstone of therapy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Its pathogenesis was clarified with the recognition that severe deficiency of ADAMTS13, a von Willebrand factor\u0026ndash;cleaving protease, underlies most cases, due to either autoantibodies or inherited mutations [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Registry data have demonstrated that rapid recognition and plasma exchange dramatically reduce mortality, bringing survival rates closer to those reported in Western cohorts [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn contrast, HUS was classically linked to Shiga toxin\u0026ndash;producing \u003cem\u003eEscherichia coli\u003c/em\u003e and presents with predominant renal injury [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Later, atypical HUS (aHUS) was identified as a complement-mediated disorder with poor renal prognosis if untreated, but dramatically altered outcomes with complement inhibitors such as eculizumab [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. This evolution highlights the importance of molecular classification for prognosis and therapy.\u003c/p\u003e\u003cp\u003eSecondary TMAs account for a substantial proportion of cases globally and are particularly common in low- and middle-income countries. Sepsis, autoimmune disorders, malignant hypertension, transplantation, and snake envenomation are recognized precipitants [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. In contrast to registries from Europe and North America\u0026mdash;where malignancy, drugs, and transplantation predominate [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u0026mdash;Indian and tropical cohorts report a significant burden of snakebite- and infection-related TMA [\u003cspan additionalcitationids=\"CR36 CR37\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. These conditions share overlapping mechanisms of endothelial injury, complement activation, and coagulation abnormalities, complicating diagnosis and management [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite advances, TMAs remain diagnostically and therapeutically challenging. Geographic variation is striking: primary TTP and complement-mediated HUS dominate in Western series [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], whereas secondary TMAs due to sepsis and snake envenomation contribute substantially in tropical countries [\u003cspan additionalcitationids=\"CR35 CR36 CR37\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Systematic evaluation of clinical spectrum, management, and outcomes in such contexts is essential to refine diagnostic strategies and improve survival. We therefore conducted a prospective observational study at a tertiary center in southern India to describe the profile, treatment, and short-term outcomes of TMA, with emphasis on the role of the PLASMIC score and the contribution of secondary TMAs to disease spectrum.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and setting\u003c/h2\u003e\u003cp\u003eWe conducted a prospective observational study at Kasturba Medical College, Manipal, between March 2024 and April 2025. Consecutive patients presenting with clinical and laboratory features suggestive of thrombotic microangiopathy (TMA) were enrolled. Ethical approval was obtained from the Institutional Ethics Committee, and written informed consent was obtained from all participants.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInclusion and exclusion criteria\u003c/h3\u003e\n\u003cp\u003eEligible patients were those with newly diagnosed TMA, defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and at least one organ involvement. Patients with pregnancy-associated TMA (preeclampsia, HELLP syndrome, or pregnancy-triggered atypical HUS) were excluded, as these syndromes represent distinct entities with unique pathophysiology and maternal\u0026ndash;fetal outcomes.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eAt baseline, demographic details, comorbidities, and clinical presentations were recorded. Laboratory parameters included hemoglobin, platelet count, lactate dehydrogenase (LDH), serum creatinine, coagulation profile, and fibrinogen. Schistocyte grading was performed on peripheral blood smears. The PLASMIC score [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] was calculated to assess the likelihood of severe ADAMTS13 deficiency. ADAMTS13 activity and Complement assays (C3, C4) were performed when a strong clinical suspicion was present.\u003c/p\u003e\n\u003ch3\u003eClassification of subtypes\u003c/h3\u003e\n\u003cp\u003ePatients were categorized as:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eTTP\u003c/b\u003e: Microangiopathic hemolytic anemia with thrombocytopenia in the absence of an alternative cause; severe ADAMTS13 deficiency (\u0026lt;\u0026thinsp;10%) confirmed the diagnosis when tested.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eHUS\u003c/b\u003e: Renal-predominant microangiopathy without severe ADAMTS13 deficiency; no Shiga toxin\u0026ndash;associated cases were identified. Where available, complement evaluation supported the diagnosis of atypical HUS or HUS of uncertain mechanism.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eSecondary TMA\u003c/b\u003e: A clear precipitating factor (e.g., sepsis, autoimmune disease, snake envenomation, malignancy, drug exposure) was present. In cases with overlapping triggers or incomplete testing, final classification was made by investigator consensus after review of all clinical, laboratory, and treatment data.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\n\u003ch3\u003eTreatment modalities\u003c/h3\u003e\n\u003cp\u003eTreatment was individualized according to institutional protocol. Plasma exchange was considered for suspected TTP and selected severe secondary TMAs. Fresh frozen plasma was administered as adjunctive therapy. Hemodialysis was performed when clinically indicated for acute kidney injury. Antisnake venom was administered in all cases of envenomation. Rituximab was used in refractory or relapsing TTP. Supportive measures included transfusion of red blood cells, infection control, and organ support as appropriate.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eOutcome assessment\u003c/h2\u003e\u003cp\u003ePatients were followed throughout the index hospitalization. The \u003cb\u003eprimary outcome\u003c/b\u003e was discharge status (recovered vs. died). \u003cb\u003eSecondary outcomes\u003c/b\u003e included the need for dialysis, renal function at discharge, and the occurrence of major in-hospital complications.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eData were analyzed using \u003cb\u003eSPSS version XX (IBM, Armonk, NY)\u003c/b\u003e. Categorical variables were expressed as proportions and compared using the Chi-square or Fisher\u0026rsquo;s exact test. Continuous variables were summarized as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median (IQR) and compared using Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test or Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test as appropriate. A \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eCohort and subtype distribution\u003c/h2\u003e\u003cp\u003eA total of 66 patients with thrombotic microangiopathy were enrolled, comprising 16 with thrombotic thrombocytopenic purpura (TTP, 24.2%), 34 with hemolytic uremic syndrome (HUS, 51.5%), and 16 with secondary TMA (24.2%). Within the secondary TMA group, the most frequent precipitants were snake envenomation (n\u0026thinsp;=\u0026thinsp;20 overall) and sepsis (n\u0026thinsp;=\u0026thinsp;15), followed by autoimmune diseases and malignant hypertension.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eBaseline characteristics (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/h2\u003e\u003cp\u003eThe mean age was highest in patients with TTP (53.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6 years), followed by secondary TMA (47.7\u0026thinsp;\u0026plusmn;\u0026thinsp;16.1 years) and HUS (43.8\u0026thinsp;\u0026plusmn;\u0026thinsp;19.0 years), though these differences were not statistically significant (p\u0026thinsp;=\u0026thinsp;0.174). Sex distribution was comparable across groups, with no significant difference in male-to-female ratios.\u003c/p\u003e\u003cp\u003eComorbidities were most frequent in TTP: hypertension was present in 37.5% and diabetes in 25%, compared with 11.8% and 17.6% respectively, in HUS, while secondary TMA had lower rates (12.5% and none, respectively). Chronic kidney disease and ischemic heart disease were rare overall, and no significant differences were observed between groups.\u003c/p\u003e\u003cp\u003ePresenting complaints varied by subtype. Fever was common in TTP (68.8%) and HUS (61.8%), but less frequent in secondary TMA (31.2%). Edema was strikingly more common in HUS (58.8%, p\u0026thinsp;=\u0026thinsp;0.0014). Abdominal distension occurred more often in TTP (25%). Neurologic manifestations were prominent in TTP and secondary TMA: altered sensorium was noted in 31.2% and 37.5% respectively, compared with only 11.8% in HUS. Seizures were documented in 12.5% of TTP and 6.2% of secondary TMA. Respiratory symptoms, such as breathlessness, occurred in one-third of TTP and secondary TMA patients, but only 11.8% of HUS. Gastrointestinal complaints, including vomiting (20\u0026ndash;31%) and diarrhea (6\u0026ndash;19%), occurred across groups without significant differences. Renal dysfunction was most pronounced in HUS, with decreased urine output reported in 29.4% of patients, compared with 12.5% in TTP and 6.2% in secondary TMA. Hematuria and jaundice were infrequent in all subtypes.\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\u003eBaseline characteristics of patients with thrombotic microangiopathy (TMA) by subtype\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTTP (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHUS (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSecondary TMA (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDemographics\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43.8\u0026thinsp;\u0026plusmn;\u0026thinsp;19.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e47.7\u0026thinsp;\u0026plusmn;\u0026thinsp;16.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.1743\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale sex, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (52.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.7494\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale sex, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (47.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.7494\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComorbidities\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0706\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType 2 diabetes, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.1207\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic kidney disease, n (%)\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\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (6.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.2046\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic heart disease, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6.2)\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\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.2046\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBronchial asthma, n (%)\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\u003e1 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.6201\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePresenting features\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFever, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (68.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (61.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (31.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0641\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBreathlessness, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (31.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (31.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.1537\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVomiting, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (20.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (31.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.7118\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiarrhea, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (18.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.5538\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAltered sensorium, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (31.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (11.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0830\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSeizures, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (12.5)\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\u003e1 (6.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.1314\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDecreased urine output, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (29.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (6.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.1118\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHematuria, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (6.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.5870\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal distension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (6.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0994\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEdema/Swelling, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (58.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (18.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.0014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eLaboratory parameters (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; Supplementary Tables\u0026nbsp;1\u0026ndash;3)\u003c/h2\u003e\u003cdiv id=\"Sec14\" class=\"Section3\"\u003e\u003ch2\u003eHematological profile\u003c/h2\u003e\u003cp\u003eBaseline hemoglobin was lowest in secondary TMA (8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 g/dL) compared with HUS (9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0 g/dL) and TTP (10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 g/dL) (p\u0026thinsp;=\u0026thinsp;0.017). Hemoglobin trends during hospitalization showed improvement across groups in patients who survived, though recovery was slower in HUS and secondary TMA. Platelet counts were uniformly depressed at baseline in all groups (mean 58\u0026ndash;66 \u0026times; 10\u0026sup3;/\u0026micro;L). Gradual recovery was observed over the first week, with median counts approaching 90\u0026ndash;145 \u0026times; 10\u0026sup3;/\u0026micro;L by day 9, particularly in HUS.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eRenal profile\u003c/h2\u003e\u003cp\u003eRenal dysfunction was most severe in HUS, with the highest admission creatinine (7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5 mg/dL, median 5.6) compared with secondary TMA (5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6 mg/dL, median 4.9) and TTP (3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9 mg/dL, median 2.4) (p\u0026thinsp;=\u0026thinsp;0.004). Serial measurements confirmed persistently higher creatinine and urea in HUS, reflecting its renal-predominant phenotype.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eHemolysis markers\u003c/h2\u003e\u003cp\u003eLDH was elevated across all groups at baseline, with the highest mean in HUS (1521 IU/L), followed by secondary TMA (1269 IU/L) and TTP (917 IU/L). Levels declined progressively with treatment but remained above reference ranges through the first week. Indirect bilirubin was mildly elevated but did not differ significantly across groups.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eCoagulation profile\u003c/h2\u003e\u003cp\u003eINR values were largely preserved in TTP and HUS but showed more variability in secondary TMA. Fibrinogen levels were frequently depressed in sepsis-associated secondary TMA, with some patients reaching undetectable values, while TTP patients generally had higher levels.\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\u003eLaboratory parameters\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTTP (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHUS (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSecondary TMA (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHematology\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin, g/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets, \u0026times;10\u0026sup3;/\u0026micro;L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57.9\u0026thinsp;\u0026plusmn;\u0026thinsp;48.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58.5\u0026thinsp;\u0026plusmn;\u0026thinsp;39.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66.2\u0026thinsp;\u0026plusmn;\u0026thinsp;48.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.797\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRenal profile\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum creatinine, mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrea, mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e94.5\u0026thinsp;\u0026plusmn;\u0026thinsp;47.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e141.8\u0026thinsp;\u0026plusmn;\u0026thinsp;66.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e138.9\u0026thinsp;\u0026plusmn;\u0026thinsp;59.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHemolysis markers\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDH, IU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e917\u0026thinsp;\u0026plusmn;\u0026thinsp;494\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1521\u0026thinsp;\u0026plusmn;\u0026thinsp;1065\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1270\u0026thinsp;\u0026plusmn;\u0026thinsp;1113\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.087\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCoagulation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrinogen, mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e196.5\u0026thinsp;\u0026plusmn;\u0026thinsp;205.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e176.3\u0026thinsp;\u0026plusmn;\u0026thinsp;128.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e228.4\u0026thinsp;\u0026plusmn;\u0026thinsp;202.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.694\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003ePLASMIC score and ADAMTS13 activity (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/h2\u003e\u003cp\u003eThe PLASMIC score stratified patients in line with clinical diagnosis. High-probability scores (6\u0026ndash;7) were observed in 87.5% of TTP cases, compared with 52.9% of HUS and only 18.8% of secondary TMA (p\u0026thinsp;=\u0026thinsp;0.002). In contrast, low scores (\u0026le;\u0026thinsp;4) clustered in secondary TMA (37.5%) and were absent in TTP.\u003c/p\u003e\u003cp\u003eADAMTS13 activity, available in 24 patients, confirmed severe deficiency (\u0026lt;\u0026thinsp;10%) in 75% of tested TTP cases, while none of the HUS or secondary TMA patients demonstrated this finding (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Intermediate reductions (10\u0026ndash;50%) were seen in a minority of TTP and non-TTP cases, whereas preserved activity (\u0026gt;\u0026thinsp;50%) was typical in HUS and secondary TMA. These results validated the PLASMIC score as a bedside surrogate when ADAMTS13 testing was unavailable.\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\u003e\u003cb\u003ePLASMIC score distribution and ADAMTS13 activity\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTTP (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHUS (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSecondary TMA (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\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\u003ePLASMIC score\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\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u0026ndash;4 (low probability)\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\u003e4 (11.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (37.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5 (intermediate probability)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (12.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (35.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (43.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.041\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u0026ndash;7 (high probability)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (87.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (52.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (18.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (6\u0026ndash;7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (5\u0026ndash;6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (4\u0026ndash;6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eADAMTS13 activity*\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\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;10% (severe deficiency)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6/8 (75.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0/10 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0/6 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u0026ndash;50%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2/8 (25.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2/10 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1/6 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.77\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;50%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0/8 (0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8/10 (80.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5/6 (83.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e*ADAMTS13 activity was performed in a subset of 24 patients based on clinical suspicion.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eTreatments\u003c/h2\u003e\u003cp\u003ePlasma exchange was performed in 14 patients (21.2%), predominantly those with TTP, although it was also used in a minority of severe secondary TMA cases, including 4 with snakebite-related disease. Fresh frozen plasma was administered in 33 patients (50.0%). Hemodialysis was required in 41 patients (62.1%), mostly among HUS and secondary TMA. All patients with snakebite-associated TMA received antisnake venom. Rituximab was administered to 2 patients with refractory or relapsing TTP.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eOutcomes (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/h2\u003e\u003cp\u003eOverall in-hospital survival was 71.2% (47/66). Subtype-specific survival was highest in HUS (82.4%, 28/34), followed by TTP (62.5%, 10/16), and lowest in secondary TMA (56.2%, 9/16). Mortality was greatest in patients with sepsis-associated secondary TMA, where multiorgan failure was the predominant cause of death. Among patients with snakebite-related TMA (n\u0026thinsp;=\u0026thinsp;20), most recovered with antisnake venom and supportive care; plasma exchange was selectively employed in 4 (20%), with good benefit.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOUTCOMES BY TMA SUBTYPE\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=\"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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTTP (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHUS (n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSecondary TMA (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurvival status\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlive at discharge, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28 (82.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9 (56.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDeaths, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6 (17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e7 (43.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective single-center study provides one of the few systematic characterizations of thrombotic microangiopathies (TMAs) from India, with particular emphasis on snakebite- and sepsis-associated disease. These secondary TMAs, seldom reported in Western cohorts, accounted for a substantial proportion of our cases and highlight the importance of region-specific data. While the clinical hallmarks of microangiopathic hemolytic anemia and thrombocytopenia were shared across subtypes, outcomes were strongly determined by the underlying etiology and the timeliness of intervention.\u003c/p\u003e\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\u003ch2\u003eDemographic and clinical profile\u003c/h2\u003e\u003cp\u003ePatients with thrombotic thrombocytopenic purpura (TTP) in our series were older (mean 53 years) and more likely to present with neurological features, consistent with reports from the International TTP Registry and the Oklahoma cohort [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Hemolytic uremic syndrome (HUS) demonstrated the greatest renal burden, with the highest creatinine and dialysis requirement, reflecting its renal-predominant phenotype and aligning with global descriptions of Shiga toxin\u0026ndash;negative and complement-mediated HUS [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Secondary TMAs accounted for one-quarter of our patients, driven predominantly by snake envenomation and sepsis. This contrasts with European and North American registries where malignancy, transplantation, and drugs predominate [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Such differences emphasize the geographic variability in TMA epidemiology and the need for local cohort data.\u003c/p\u003e\u003cdiv id=\"Sec23\" class=\"Section3\"\u003e\u003ch2\u003eLaboratory features and risk stratification\u003c/h2\u003e\u003cp\u003eHematologic indices at baseline reflected the systemic burden of microangiopathy. Anemia was universal but most pronounced in secondary TMAs, in keeping with prior reports that systemic inflammation and consumptive processes amplify hemolysis in infection- and malignancy-related disease [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. TTP patients, in contrast, often maintained comparatively higher hemoglobin, similar to observations from the Oklahoma TTP Registry where anemia was less severe than in renal-predominant forms [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Platelet counts were profoundly reduced across all groups, but recovery patterns diverged: in our series, HUS patients demonstrated more rapid platelet recovery by day, while recovery in TTP and secondary TMAs was delayed. This echoes registry findings that hematologic remission is often achieved earlier in complement-mediated HUS than in antibody-mediated TTP, despite comparable initial thrombocytopenia [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRenal parameters clearly differentiated the subtypes. Patients with HUS showed the highest creatinine and urea levels throughout hospitalization, underscoring the renal-dominant phenotype described in classical and atypical HUS cohorts [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. TTP patients generally exhibited only modest renal dysfunction, paralleling international registry data where neurologic rather than renal features predominated [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Secondary TMAs displayed intermediate renal involvement, consistent with heterogeneous etiologies ranging from sepsis to envenomation, which have been shown in prior Indian series to carry variable but often significant renal burden [\u003cspan additionalcitationids=\"CR36 CR37\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMarkers of hemolysis were elevated across all groups, with LDH remaining above normal despite clinical improvement. Persistent LDH elevation despite hematologic recovery has been highlighted in both the French TMA Registry and the International TTP Registry as evidence of ongoing endothelial injury [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The highest levels were seen in HUS and secondary TMAs, consistent with more severe organ involvement. Indirect bilirubin showed only modest differences, echoing prior reports where LDH is the more sensitive marker of ongoing microangiopathy [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCoagulation profiles provided additional distinction. In TTP, INR and fibrinogen were generally preserved, in line with the absence of consumptive coagulopathy described in immune-mediated TTP [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. By contrast, secondary TMAs\u0026mdash;particularly those associated with sepsis\u0026mdash;exhibited hypofibrinogenemia and variable INR elevation, reflecting overlap with disseminated intravascular coagulation [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. This mirrors earlier descriptions by George et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and Levi et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], where sepsis-associated TMA frequently displayed laboratory features intermediate between classical TMA and DIC.\u003c/p\u003e\u003cp\u003eRisk stratification using the PLASMIC score aligned well with clinical phenotypes. High-probability scores clustered in TTP, enabling rapid recognition and initiation of plasma exchange even before ADAMTS13 confirmation. Similar utility of the PLASMIC score as an early surrogate for severe ADAMTS13 deficiency has been demonstrated in North American and European cohorts [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the subset of patients tested, severe ADAMTS13 deficiency was confined to suspected TTP, validating both the score and the clinical classification. This concordance parallels findings from the International TTP Registry and other validation studies, underscoring the global relevance of bedside scoring even in resource-limited settings [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\u003ch2\u003eTreatment\u003c/h2\u003e\u003cp\u003eTherapy was tailored to subtype and resource availability. Plasma exchange was performed in 14 patients, predominantly with TTP, reaffirming its status as the standard of care [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Fresh frozen plasma was administered in half the cohort, largely as supportive therapy. Dialysis was required in over 60% of patients, particularly in HUS and secondary TMA, underscoring the renal burden. Rituximab was used in two patients with refractory TTP[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], but advanced therapies such as caplacizumab and eculizumab were unavailable, contrasting with contemporary Western practice [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This gap underscores the challenge of equitable access to novel agents in low- and middle-income countries.\u003c/p\u003e\u003cp\u003eSnakebite-associated TMA is a distinctive strength of this study. All 20 patients received antisnake venom, with generally favorable short-term survival. Plasma exchange was selectively used in 20%, reflecting a pragmatic approach to refractory cases. Similar findings have been reported in recent Indian series: Sahay et al. (2018) described viper bite\u0026ndash;related TMA requiring dialysis in most cases, with plasma exchange used selectively [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], while Patil et al. (2020) highlighted improved renal and hematologic recovery with early therapeutic plasma exchange [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. More recently, Sukumar et al. (2020) emphasized the contribution of microangiopathy to snakebite-associated acute kidney injury and the role of supportive care including dialysis and plasma exchange in selected patients [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur prospective data therefore complement these reports, supporting that plasma exchange is not universally required but may benefit patients with severe or refractory presentations[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSepsis-associated TMA carried the highest mortality in our series. The overlap between endothelial injury, complement activation, and disseminated intravascular coagulation makes both diagnosis and management challenging. Recent work has emphasized that sepsis can trigger a TMA-like phenotype distinct from classical DIC. George (2020) described sepsis-associated TMA as an underrecognized entity requiring careful differentiation from DIC [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], while Levi et al. (2020) highlighted the complex interplay of coagulation and inflammation in septic microangiopathy [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. These observations parallel our findings, where mortality was driven largely by multiorgan dysfunction despite supportive therapy.\u003c/p\u003e\u003cdiv id=\"Sec25\" class=\"Section3\"\u003e\u003ch2\u003ePrognosis and survival\u003c/h2\u003e\u003cp\u003eOverall in-hospital survival was 71.2%, comparable to international cohorts [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. However, subtype-specific outcomes differed. Survival in TTP (62.5%) was lower than registry figures of ~\u0026thinsp;80\u0026ndash;90% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], reflecting delayed recognition and limited access to caplacizumab or early rituximab. HUS survival (82.4%) was reasonable but lower than outcomes reported with eculizumab [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Secondary TMA had the poorest outcomes (56.2% survival), driven by sepsis-related mortality, in line with evidence that prognosis in secondary TMAs is dictated by the underlying trigger rather than the microangiopathy itself [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Snakebite-associated cases fared relatively better with antisnake venom and supportive care, highlighting an important distinction between tropical and Western etiologies [\u003cspan additionalcitationids=\"CR36 CR37\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec26\" class=\"Section3\"\u003e\u003ch2\u003eStrengths and limitations\u003c/h2\u003e\u003cp\u003eStrengths of this study include its prospective design, systematic classification, and detailed evaluation of secondary TMAs relevant to tropical countries. Limitations include modest sample size, single-center setting, lack of long-term renal follow-up, and restricted access to molecular diagnostics. The absence of novel agents such as eculizumab and caplacizumab limited comparisons with outcomes in high-income settings.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOutcomes in TMA were determined more by underlying etiology and timeliness of therapy than by any single laboratory marker. The PLASMIC score proved highly effective for bedside risk stratification and guided early plasma exchange in suspected TTP. HUS carried the greatest renal burden, requiring intensive dialysis support, while secondary TMAs were dominated by snakebite and sepsis, reflecting the regional epidemiology. Snakebite-associated cases generally responded well to antisnake venom and supportive care, whereas sepsis-associated TMA had the highest mortality. These findings highlight the importance of early recognition, rapid initiation of plasma exchange in TTP, and context-specific strategies to address the burden of secondary TMAs in low- and middle-income countries.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics Approval and Consent to Participate\u003c/h2\u003e\n\u003cp\u003eThe study was approved by the Institutional Ethics Committee, Kasturba Medical College, Manipal (IEC 2:648/2023). The study was conducted in accordance with the Declaration of Helsinki and its later amendments. Written informed consent was obtained from all participants.\u003c/p\u003e\n\u003ch2\u003eConflict of Interest Statement\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing financial or personal interests that could have influenced the work reported in this manuscript.\u003c/p\u003e\n\u003ch2\u003eFunding Statement\u003c/h2\u003e\n\u003cp\u003eNo external funding was received for this study.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eDr Jagadeesh Mullapudi conceived and designed the study, collected and analyzed data, and drafted the manuscript.\u003c/p\u003e\n\u003cp\u003eDr Ram Bhat supervised the study and critically reviewed the manuscript.All authors approved the final version.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eData supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGeorge JN, Nester CM. 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Indian J Nephrol. 2024;34(2):145\u0026ndash;52. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/ijn.ijn_2024_18\u003c/span\u003e\u003cspan address=\"10.4103/ijn.ijn_2024_18\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Thrombotic microangiopathy (TMA), Thrombotic thrombocytopenic purpura (TTP), Hemolytic uremic syndrome (HUS), PLASMIC score, ADAMTS13, Snakebite, Sepsis, India, Plasma Exchange","lastPublishedDoi":"10.21203/rs.3.rs-7744574/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7744574/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThrombotic microangiopathies (TMAs) are rare but life-threatening syndromes characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction. While thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) dominate Western cohorts, secondary TMAs due to snake envenomation and sepsis are increasingly recognized in tropical regions. We conducted a prospective study to evaluate the clinical spectrum, laboratory features, risk stratification, treatment, and outcomes of TMA in an Indian tertiary care setting.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eConsecutive patients with newly diagnosed TMA were enrolled between March 2024 and April 2025. Patients were categorized as TTP, HUS, or secondary TMA. Demographic, clinical, and laboratory data were recorded. PLASMIC scores were calculated, and ADAMTS13 activity was assessed where feasible. Treatment strategies, including plasma exchange, dialysis, antisnake venom, and supportive care, were documented. The primary outcome was discharge status (recovered vs. died).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eSixty-six patients were included: TTP (n\u0026thinsp;=\u0026thinsp;16), HUS (n\u0026thinsp;=\u0026thinsp;34), and secondary TMA (n\u0026thinsp;=\u0026thinsp;16). Patients with TTP were older and more likely to present with neurologic symptoms, whereas HUS demonstrated the highest renal burden and dialysis requirement. Secondary TMAs were predominantly due to snakebite (n\u0026thinsp;=\u0026thinsp;20) and sepsis (n\u0026thinsp;=\u0026thinsp;17). Hemoglobin was lowest in secondary TMA, creatinine was highest in HUS, and LDH was elevated across all subtypes. The PLASMIC score effectively stratified TTP, with severe ADAMTS13 deficiency confirmed in most tested cases. Plasma exchange was performed in 14 patients (mainly TTP), while all snakebite cases received antisnake venom, 4 patients received plasma exchange. Overall survival was 71.2%: HUS 82.4%, TTP 62.5%, and secondary TMA 56.2%. Mortality was highest in sepsis-associated TMA.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn this prospective Indian cohort, TMA presented with distinct subtype-specific patterns. The PLASMIC score enabled early recognition of TTP, while snakebite- and sepsis-associated TMAs contributed substantially to disease burden and outcomes. These findings highlight the need for context-specific strategies for TMA management in tropical settings.\u003c/p\u003e","manuscriptTitle":"Clinical Profile and Outcomes of Thrombotic Microangiopathy - A Prospective Study From a Tertiary Centre in India","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-30 07:04:18","doi":"10.21203/rs.3.rs-7744574/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a3b2d7d7-b997-4451-983e-0d69566dd26b","owner":[],"postedDate":"October 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-09T23:08:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-30 07:04:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7744574","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7744574","identity":"rs-7744574","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}