Time-Course of Platelets Count in Children with Hemolytic Uremic Syndrome. Data from the ItalKid-HUS Network.

Time-Course of Platelets Count in Children with Hemolytic Uremic Syndrome. Data from the ItalKid-HUS Network. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Time-Course of Platelets Count in Children with Hemolytic Uremic Syndrome. Data from the ItalKid-HUS Network. Daniele Rossetti, Daniele Di Luise, Maria Cristina Mancuso, Giacomo Tamburini, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8432171/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Hemolytic uremic syndrome (HUS) related to Shiga toxin-producing Escherichia Coli (STEC) infection is a severe, life-threatening thrombotic microangiopathy (TMA). Endothelial damage causes platelet consumption and consequently platelet count is a key biomarker for monitoring disease activity. The present paper describes the time course of platelet count in a cohort of patients with STEC-HUS in order to provide references helpful in identifying subjects who divert from the expected course because complications. Methods All children treated at our Center with a well-established diagnosis of STEC-HUS during the period 2010–2025 were retrospectively enrolled and platelets count was recorded until discharge. The nadir of platelets count for each patient was used to align the results and investigate the time course towards platelets normalization. The cumulative percentage of platelets normalization was calculated on daily basis, together with the 10th centile of platelets count. Result During the 16 years under investigation, a total of 148 children were enrolled. The nadir of platelets count was 23,000/mm3 (IQR 14,000–39,000) on day 8 since the beginning of symptoms. By day 14 from the nadir, 100% of patients had reached a platelets count > 150.000/mm3. Conclusions Given that STEC-HUS is a self-limiting disease, the related TMA is expected to spontaneously cease within a defined time. If platelets count has a different course from the expected, the patient is likely to have complications that need to be actively searched for and treated accordingly (e.g. atypical HUS, disseminated intravascular coagulation or heparin induced thrombocytopenia). Platelets HUS STEC TMA Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Hemolytic uremic syndrome (HUS), in its typical form caused by Shiga Toxin-producing Escherichia Coli (STEC-HUS), is the most common thrombotic micro-angiopathy (TMA) affecting previously healthy children and it is defined by the concomitant occurrence of platelets consumption, hemolysis and kidney damage. 1 , 2 Despite significant advances in the scientific knowledge and medical technology, the disease remains a major individual and public health challenge worldwide. The disease follows an intestinal infection by STEC, most commonly (> 80% of cases) associated with blood in stools, and it has a relatively regular course: after an incubation period of 3–8 days from bacteria ingestion, secretive diarrhea (variably associated with abdominal pain, vomiting and fever) is observed. 3 After 24–48 hours from the onset of initial symptoms, blood in stools appears. The majority of patients will recover from diarrhea within 5–6 days, while in about 15% of infected patients the disease eventually turns into HUS. 4 This condition is characterized by a case-fatality rate ranging between 1–5%, need of renal replacement therapy for some days in 30–60% of cases, central nervous system (CNS) involvement in 10–25% of cases, intensive care support in 10–30% of patients and long term sequels (renal, neurologic, intestinal) are not rare (20–30%). 5 The disease has no specific treatment and supportive care is the only therapeutic opportunity. 6,7 With this regard, the days between TMA onset and remission are the most critical ones as to need of care. Timely understanding of the disease progression in individual cases might be crucial for clinical decision making. 8 Platelets (PLT) count, more than any other laboratory parameter, can better represent the time course of the TMA in order to anticipate and predict its evolution. Moreover, a detailed knowledge of the PLT count time course in this disease enables the rapid identification of patients whose condition is not progressing as expected towards spontaneous recovery, raising the suspicion that a complication may have occurred. This paper is aimed at describing and sharing the time-course of PLT count towards the TMA resolution in a cohort of patients with uncomplicated STEC-HUS. Materials and Methods All children diagnosed with STEC-HUS at our Center since 2010 were considered for the present analysis. The diagnosis of HUS was based on the concomitant presence of PLT consumption, hemolysis and kidney damage. The diagnosis of STEC infection was based on the detection of Stx encoding genes by PCR in stools. Patients who tested negative for Stx genes but were positive for serum ant-lypopolysaccharide for the “top 6” serotypes (O157, O26, O103, O111, O145 and O104) were considered as confirmed STEC-HUS cases if negative for antiCFH autoantibodies or for complement regulatory gene variants. Patients with atypical HUS (aHUS) were excluded from the analysis. Patients who died before reaching normal PLT count were also excluded. For each enrolled patient the following information was recorded: sex, date of birth, date of symptoms onset, date of bloody diarrhea onset, date of HUS diagnosis, laboratory at diagnosis and all available platelet counts throughout the disease until discharge. The need for renal replacement therapy as well as eventual CNS involvement and the laboratory results at restitutio ad integrum or at 2 years after the disease onset was also recorded. Patients or parents (as applicable) gave their informed consent to participate in the study, which was authorized by our institutional Ethical Committee (Registration number 129/10). Laboratory investigations STEC-related genes were searched for by the Reverse Dot Blot Assay (Genotype EHEC, Arnika) until 2018, followed by multiplex Real-Time PCR (R-biopharm) untill 2021. In 2021 the method of detection of Stx related genes changed, moving to Seegen multiplex panel for screening. Since 2023, a syndromic panel (QIAstat-Dx Gastrointestinal Panel 2) has been used. Patients with negative PCR for Stx were tested for anti-lipopolysaccharide antibodies for the “top 6” serotypes (O157, O26, O103, O111, O145, and O104). Blood count was performed using a XN-9000 hematology analyzer. All samples analyzed with PLT-I (impedance method) count and flag of platelet abnormal distribution were automatically reanalyzed with PLT-F (fluorescence method). Rules were defined in the middle-ware Sysmex Extended Information Processing Unit (Sysmex Europe GMBH, Norderstadt, Germany). Data Analysis Data are provided in absolute numbers and percent or as median and IQR, as appropriate. For each patient, whenever a PLT count was missing (not measured) in a given day, we imputed it by calculating the geometric mean of PLT values of the day before and the day after. The median value of PLT count and the 10th centile were also calculated, day by day after patients had reached the nadir of PLT count. The cumulative proportion of PLT normalization was also calculated. Analyses were carried out using either StatView SE+ (Abacus Concepts INC, 1988) and R version 4.5.0 (R Core Team, 2025) within RStudio version 2025.05.1 + 513 (Posit Software, PBC). Results A total of 183 patients were initially enrolled in the study. Six cases were excluded because they carried pathogenic complement regulatory genes variants (atypical HUS). Twelve patients were excluded because the nadir of PLTs count was not identifiable (the lowest PLT count coincided with the first determination). Two cases had fatal outcome before reaching normal PLT count. Fifteen additional patients were excluded due to missing data critical for the study. The cohort under investigation included 148 patients (85 female; 57.4%) with median age of 3.0 years (1.7–6.7). Stx 2 was the most common cause of HUS (n: 86; 58.1%), while Stx1 + 2 were identified in 25 (16.9%) of cases. In 1 patient (0.7%) only, Stx1 alone was detected. In 36 patients (24.3%) the Stx was not identified initially, but the diagnosis of STEC infection was made based on antiLPS antibodies (19 cases) or on the symptoms occasionally associated with family members positive to Stx (other 17 cases). Table 1 shows relevant TMA parameters at HUS diagnosis; in details median PLT count was 62x10 3 /ul (IQR 36.0-87.5). Sixty-one patients (41.2%) required renal replacement therapy (hemodialysis) with a median duration of 6 days (IQR 3–9). In 13 cases, (8.8%) overt CNS involvement was observed. All these data are summarized in table 1. The analysis of PLTs count was based on a total of 1245 values of PLT (mean of 8.4 determination for patient). The median nadir of PLT count was 23x10 3 /mm3 (IQR 14–39) and it was reached in 8 days from onset of symptoms (table 1). The distribution of the PLT count at the nadir and the corresponding box-plot is shown in Fig. 1. The cumulative proportion of PLTs normalization (Fig. 2) shows that 50% of patients had reached normal PLT count by day 5 and 100% by day 14 from the nadir. Figure 3 describes the time course, day by day, of PLT count as lower limit (10th centile) during the recovery period (after the nadir of PLT count). At day 9 from the nadir PLT count, 9 out of 10 patients reached the normal value of 150.000/mm 3 . Figure 4 shows the key time points of STEC-HUS from the beginning of abdominal symptoms, as observed in the 148 investigated patients with special regard to the time-course of PLT count. In particular, the nadir was reached on day 8. By day 14 half of the patients had normalized their PLT count and by day 25 all had normal PLT count. Discussion The diagnosis of STEC-HUS is based on the classic diagnostic triad (platelet consumption, hemolysis, and kidney damage) in association with a STEC-proven gastrointestinal infection. 1 On the contrary, atypical HUS is an exclusion diagnosis, if the mentioned triad is present and STEC infection and Thrombotic Thrombocytopenic Purpura (and few other ultrarare conditions) have been ruled out. 9 This nomenclature has been recently criticized, in favor of a classification more consistent with the advancement of knowledge in this area and based on the etiology of each entity. 10 Unfortunately, aHUS often complicates other conditions, such as infections, that may represent a trigger for complement disregulating abnormalities (genetic or acquired). Therefore, STEC infection, besides causing STEC-HUS may well trigger aHUS if the patient carries one or more of the mentioned abnormalities. Indeed, variants in complement regulatory genes are not so rare and consequently STEC infections could occur in subjects at risk of developing aHUS as a consequence of the infection. 11 Whenever STEC infection and aHUS coexist in the same subject, a diagnostic dilemma is generated with potential serious consequences. In the described setting the differential diagnosis may be very challenging because all the laboratory parameters traditionally used for assessing TMA (haptoglobin, LDH, bilirubin, proteinuria, hematuria, thrombocytopenia, schistocytes, hemoglobin, etc.) will be indistinguishable in the two diseases. However, while STEC-HUS is a self-limiting condition and the TMA is expected to spontaneously resolve within days, aHUS due to complement dysregulation, most commonly, does not resolve spontaneously and, if untreated, the majority of patients will require chronic dialysis due to the persisting microangiopathic process. 12 We believe that the PLT count, better than any other biomarkers, can be useful to identify the coexistence of the 2 conditions by revealing an inconsistent time-course during recovery. The carefully monitoring platelet count during the recovery phase of STEC-related HUS may reveal a derangement from “normal” course that should raise suspicion of aHUS or of other conditions complicating STEC-HUS. namely superimposed infections or heparin-induced thrombocytopenia. All these conditions are associated with PLT consumption that will interfere with the recovery from STEC-HUS. However, in order to identify a derangement from the natural course, a reference paradigm is needed and, to the best of our knowledge, such a paradigm is missing. The present paper is an attempt to provide reference values for PLT count in STEC-HUS based on data from 148 patients. In details, we underline that 100% of patients with STEC-HUS have reached a normal PLT count by day 14 from the nadir. Moreover, the 10th centile of PLT count day by day is provided as limit below which other diagnostic options should be considered. Conclusion In conclusion we offer clinicians a reference value of platelets count day by day as expected during the recovery phase of uncomplicated STEC-HUS to guide them in correctly evaluating the trend towards normalization that is expected in all patients within 14 days from the nadir value that is reached at a median of 8 days since the onset of symptoms. Abbreviations HUS Hemolytic uremic syndrome aHUS Atypical Hemolytic uremic syndrome STEC Shiga Toxin-producing Escherichia Coli TMA Thrombotic Micro-Angiopathy CNS Central Nervous System PLT Platelet Declarations Address correspondence to Daniele Rossetti, Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Della Commenda 9, Milan, 20122, Italy ( [email protected] ) Conflict of interest The authors declare no competing interests. Funding statement No funding was provided to perform this study. Acknowledgements: We wish to express our sincere gratitude to the following members of the ItalKid-HUS Network for their valuable collaboration and their commitment to the screening of patients presenting with acute bloody diarrhea: Fiorella Acquotta, Paolo Adamoli, Nicola Altamura, Angela Amoroso, Stefano Andreoni, Massimo Andreotti, Maddalena Antolini, Milana Arghittu, Francesca Atzeri, Carlo Baldioli, Barbara Balduzzi, Irene Benini, Simone Benvenuto, Francesco Beretta, Cristina Bertulli, Valeria Besutti, Lorenzo Biscardi, Annalisa Bonazza, Cristina Bonetti, Annalisa Bosco, Grazia Bossi, Marta Brambilla, Maria Francesca Brambillasca, Valentina Burzio, Anna Elisabetta Bussolini, Elena Cama, Patrizia Carlucci, Maria Carrabba, Maria Luisa Casciana, Daniela Casnaghi, Eleonora Castellone, Valeria Castorani, Marco Cazzaniga, Claudio Cavalli, Lisa Lucia Chenal, Rosaria Celano, Rossella Ceruti, Marta Cerutti, Giulia Cesano, Giulia Chiopris, Anna Cogliardi, Giacomo Colella, Lucia Collini, Rosaria Colombo, Dario Consonni, Crescenzo Coppola, Angela Corna, Annalisa Corti, Giorgia Daffunchio, Simona De Franco, Elena Lucia De Rose, Laura Dell’Era, Giulia Dilio, Clelia Di Mari, Sandra Esposito, Diana Fanti, Alessandra Ferrari, Ilaria Frugnoli, Maria Forestieri, Gloria Fumagalli, Maria Rita Gallina, Miriam Chiara Gatto, Claudio Giacomazzi, Stefano Grossi, Silvia Grosso, Chiara Gualeni, Elisa La Barba, Anna Maria La Pusata, Sara La Rosa, Annalisa Lastrico, Alberto Lepre, Francesca Lizzoli, Rosa Maria Maccarone, Anna Madera, Laura Martelli, Elena Mazzali, Elisabetta Mazzola, Marcella Mercuri, Elisa Milanesi, Chiara Minini, Paola Mirri, Sonia Monticone, Alice Monzani, Vincenza Morinello, Arianna Moroni, Maria Carmela Musolino, Maria Amata Negri, Stefano Nespoli, Bianca Osnaghi, Elisabetta Pagani, Franca Pagani, Cristina Partenope, Palmiro Pedroni, Giovanni Raimondo Pieri, Maria Antonietta Piscopo, Stefano Poli, Ilaria Possenti, Giulia Ramponi, Agrippino Reciputo, Barbara Roman, Barbara Ronchi, Chiara Rosazza, Elena Rossi, Claudia Ruggieri, Maria Lorena Ruzza, Filippo Salvini, Letizia Sardella, Martina Scali, Chiara Sciuto, Alessandra Scolari, Micaela Silvestri, Daniela Simoncini, Giulia Smylie, Rosa Maria Taibi, Francesca Tel, Sara Testa, Valentina Todescato, Elena Tommasoni, Paola Tommasi, Gaia Vanzù, Antonio Vergori, Federica Vianello, Chiara Vismara, Chiara Zambetti. Data availability Data will be made available upon reasonable request. References Ardissino G, Possenti I, Tel F, Testa S, Paglialonga F (2014) Time to change the definition of hemolytic uremic syndrome. European Journal of Internal Medicine vol. 25 Preprint at https://doi.org/10.1016/j.ejim.2013.12.002 Fakhouri F, Zuber J, Frémeaux-Bacchi V, Loirat C (2017) Haemolytic uraemic syndrome. The Lancet vol. 390 681–696 Preprint at https://doi.org/10.1016/S0140-6736(17)30062-4 Awofisayo-Okuyelu A, Brainard J, Hall I, McCarthy N (2019) Incubation Period of Shiga Toxin-Producing Escherichia coli. Epidemiologic Reviews vol. 41 121–129 Preprint at https://doi.org/10.1093/epirev/mxz001 Ardissino G et al (2021) Bloody Diarrhea and Shiga Toxin–Producing Escherichia coli Hemolytic Uremic Syndrome in Children: Data from the ItalKid-HUS Network. J Pediatr 237 Michael M, Bagga A, Sartain SE, Smith RJH (2022) Haemolytic uraemic syndrome. The Lancet vol. 400 1722–1740 Preprint at https://doi.org/10.1016/S0140-6736(22)01202-8 Ardissino G et al (2016) Early volume expansion and outcomes of hemolytic uremic syndrome. Pediatrics 137 Tarr PI, Gordon CA, Chandler WL (2005) Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. in Lancet vol. 365 1073–1086Elsevier B.V Maleknia L et al (2025) Predicting Progression of STEC-HUS: Use of Shiga Toxin Subtype and Routine Laboratory Screening. J Pediatr Infect Dis Soc 14 Kavanagh D et al (2024) Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum. Kidney Int 106:1038–1050 Nester CM et al (2024) An expert discussion on the atypical hemolytic uremic syndrome nomenclature—identifying a road map to precision: a report of a National Kidney Foundation Working Group. Kidney Int 106:326–336 Frémeaux-Bacchi V et al (2019) Complement gene variants and shiga toxin-producing escherichia coli-associated hemolytic uremic syndrome retrospective genetic and clinical study. Clin J Am Soc Nephrol 14:364–377 Ardissino G et al (2024) Outcome of atypical hemolytic uremic syndrome: role of triggers and complement abnormalities in the response to C5 inhibition. J Nephrol 37:1017–1026 Tables Table 1 is available in the Supplementary Files section. Supplementary Files Table1.pdf ethicscommittee.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major Revisions Needed 16 Feb, 2026 Reviewers agreed at journal 20 Jan, 2026 Reviewers invited by journal 15 Jan, 2026 Editor assigned by journal 14 Jan, 2026 First submitted to journal 14 Jan, 2026 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-8432171","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":575094273,"identity":"50403e80-a9f2-47fc-825c-a6e803640f87","order_by":0,"name":"Daniele 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14:50:31","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":54860,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8432171/v1/9f9f471b693217c18285bf1d.html"},{"id":100695003,"identity":"7cf38d7b-e5f0-4cd7-902c-5adfe73fa086","added_by":"auto","created_at":"2026-01-20 14:49:42","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":202493,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"11.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8432171/v1/1f11ea3a80fc35a0f29e4249.jpg"},{"id":100695163,"identity":"5747dae8-c302-48fd-837a-43db923f57db","added_by":"auto","created_at":"2026-01-20 14:51:28","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":299258,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"12.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8432171/v1/d1342109f96fe14a1b58c3e6.jpg"},{"id":100695066,"identity":"734c7b29-ce60-49cd-ad37-658869b53320","added_by":"auto","created_at":"2026-01-20 14:50:34","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":270615,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"13.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8432171/v1/4bdb2c62f9139bac8c24adb2.jpg"},{"id":100694923,"identity":"44822feb-ba73-49e6-8db2-c9808c05173b","added_by":"auto","created_at":"2026-01-20 14:48:09","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":300961,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"14.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8432171/v1/04c57f81663020cfcbc43cfa.jpg"},{"id":100702798,"identity":"69922417-7f67-42ad-93dd-8ce06ea09352","added_by":"auto","created_at":"2026-01-20 16:23:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1513915,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8432171/v1/8e7a365f-95b6-47ce-a8fc-27632386259c.pdf"},{"id":100694910,"identity":"088b2d6e-90c1-4bb1-9f42-0d4b252db878","added_by":"auto","created_at":"2026-01-20 14:47:52","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":119201,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8432171/v1/b5e4537c031d4bbc9dbbd050.pdf"},{"id":100694917,"identity":"e2d26444-fe61-47be-9dd1-93e215fc8434","added_by":"auto","created_at":"2026-01-20 14:48:04","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":2734762,"visible":true,"origin":"","legend":"","description":"","filename":"ethicscommittee.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8432171/v1/c322835225c95984439d2872.pdf"}],"financialInterests":"","formattedTitle":"Time-Course of Platelets Count in Children with Hemolytic Uremic Syndrome. Data from the ItalKid-HUS Network.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHemolytic uremic syndrome (HUS), in its typical form caused by Shiga Toxin-producing Escherichia Coli (STEC-HUS), is the most common thrombotic micro-angiopathy (TMA) affecting previously healthy children and it is defined by the concomitant occurrence of platelets consumption, hemolysis and kidney damage.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Despite significant advances in the scientific knowledge and medical technology, the disease remains a major individual and public health challenge worldwide. The disease follows an intestinal infection by STEC, most commonly (\u0026gt;\u0026thinsp;80% of cases) associated with blood in stools, and it has a relatively regular course: after an incubation period of 3\u0026ndash;8 days from bacteria ingestion, secretive diarrhea (variably associated with abdominal pain, vomiting and fever) is observed.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e After 24\u0026ndash;48 hours from the onset of initial symptoms, blood in stools appears. The majority of patients will recover from diarrhea within 5\u0026ndash;6 days, while in about 15% of infected patients the disease eventually turns into HUS.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e This condition is characterized by a case-fatality rate ranging between 1\u0026ndash;5%, need of renal replacement therapy for some days in 30\u0026ndash;60% of cases, central nervous system (CNS) involvement in 10\u0026ndash;25% of cases, intensive care support in 10\u0026ndash;30% of patients and long term sequels (renal, neurologic, intestinal) are not rare (20\u0026ndash;30%).\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe disease has no specific treatment and supportive care is the only therapeutic opportunity. \u003csup\u003e6,7\u003c/sup\u003e With this regard, the days between TMA onset and remission are the most critical ones as to need of care. Timely understanding of the disease progression in individual cases might be crucial for clinical decision making. \u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePlatelets (PLT) count, more than any other laboratory parameter, can better represent the time course of the TMA in order to anticipate and predict its evolution. Moreover, a detailed knowledge of the PLT count time course in this disease enables the rapid identification of patients whose condition is not progressing as expected towards spontaneous recovery, raising the suspicion that a complication may have occurred.\u003c/p\u003e \u003cp\u003eThis paper is aimed at describing and sharing the time-course of PLT count towards the TMA resolution in a cohort of patients with uncomplicated STEC-HUS.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eAll children diagnosed with STEC-HUS at our Center since 2010 were considered for the present analysis. The diagnosis of HUS was based on the concomitant presence of PLT consumption, hemolysis and kidney damage. The diagnosis of STEC infection was based on the detection of Stx encoding genes by PCR in stools. Patients who tested negative for Stx genes but were positive for serum ant-lypopolysaccharide for the \u0026ldquo;top 6\u0026rdquo; serotypes (O157, O26, O103, O111, O145 and O104) were considered as confirmed STEC-HUS cases if negative for antiCFH autoantibodies or for complement regulatory gene variants. Patients with atypical HUS (aHUS) were excluded from the analysis. Patients who died before reaching normal PLT count were also excluded.\u003c/p\u003e \u003cp\u003eFor each enrolled patient the following information was recorded: sex, date of birth, date of symptoms onset, date of bloody diarrhea onset, date of HUS diagnosis, laboratory at diagnosis and all available platelet counts throughout the disease until discharge. The need for renal replacement therapy as well as eventual CNS involvement and the laboratory results at restitutio ad integrum or at 2 years after the disease onset was also recorded.\u003c/p\u003e \u003cp\u003e Patients or parents (as applicable) gave their informed consent to participate in the study, which was authorized by our institutional Ethical Committee (Registration number 129/10).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory investigations\u003c/h2\u003e \u003cp\u003eSTEC-related genes were searched for by the Reverse Dot Blot Assay (Genotype EHEC, Arnika) until 2018, followed by multiplex Real-Time PCR (R-biopharm) untill 2021. In 2021 the method of detection of Stx related genes changed, moving to Seegen multiplex panel for screening. Since 2023, a syndromic panel (QIAstat-Dx Gastrointestinal Panel 2) has been used.\u003c/p\u003e \u003cp\u003ePatients with negative PCR for Stx were tested for anti-lipopolysaccharide antibodies for the \u0026ldquo;top 6\u0026rdquo; serotypes (O157, O26, O103, O111, O145, and O104).\u003c/p\u003e \u003cp\u003eBlood count was performed using a XN-9000 hematology analyzer. All samples analyzed with PLT-I (impedance method) count and flag of platelet abnormal distribution were automatically reanalyzed with PLT-F (fluorescence method). Rules were defined in the middle-ware Sysmex Extended Information Processing Unit (Sysmex Europe GMBH, Norderstadt, Germany).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eData are provided in absolute numbers and percent or as median and IQR, as appropriate. For each patient, whenever a PLT count was missing (not measured) in a given day, we imputed it by calculating the geometric mean of PLT values of the day before and the day after. The median value of PLT count and the 10th centile were also calculated, day by day after patients had reached the nadir of PLT count. The cumulative proportion of PLT normalization was also calculated. Analyses were carried out using either StatView SE+ (Abacus Concepts INC, 1988) and R version 4.5.0 (R Core Team, 2025) within RStudio version 2025.05.1\u0026thinsp;+\u0026thinsp;513 (Posit Software, PBC).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 183 patients were initially enrolled in the study. Six cases were excluded because they carried pathogenic complement regulatory genes variants (atypical HUS). Twelve patients were excluded because the nadir of PLTs count was not identifiable (the lowest PLT count coincided with the first determination). Two cases had fatal outcome before reaching normal PLT count.\u003c/p\u003e \u003cp\u003eFifteen additional patients were excluded due to missing data critical for the study. The cohort under investigation included 148 patients (85 female; 57.4%) with median age of 3.0 years (1.7\u0026ndash;6.7). Stx 2 was the most common cause of HUS (n: 86; 58.1%), while Stx1\u0026thinsp;+\u0026thinsp;2 were identified in 25 (16.9%) of cases. In 1 patient (0.7%) only, Stx1 alone was detected. In 36 patients (24.3%) the Stx was not identified initially, but the diagnosis of STEC infection was made based on antiLPS antibodies (19 cases) or on the symptoms occasionally associated with family members positive to Stx (other 17 cases). Table\u0026nbsp;1 shows relevant TMA parameters at HUS diagnosis; in details median PLT count was 62x10\u003csup\u003e3\u003c/sup\u003e/ul (IQR 36.0-87.5). Sixty-one patients (41.2%) required renal replacement therapy (hemodialysis) with a median duration of 6 days (IQR 3\u0026ndash;9). In 13 cases, (8.8%) overt CNS involvement was observed. All these data are summarized in table 1.\u003c/p\u003e \u003cp\u003eThe analysis of PLTs count was based on a total of 1245 values of PLT (mean of 8.4 determination for patient).\u003c/p\u003e \u003cp\u003eThe median nadir of PLT count was 23x10\u003csup\u003e3\u003c/sup\u003e/mm3 (IQR 14\u0026ndash;39) and it was reached in 8 days from onset of symptoms (table 1). The distribution of the PLT count at the nadir and the corresponding box-plot is shown in Fig.\u0026nbsp;1.\u003c/p\u003e \u003cp\u003eThe cumulative proportion of PLTs normalization (Fig.\u0026nbsp;2) shows that 50% of patients had reached normal PLT count by day 5 and 100% by day 14 from the nadir.\u003c/p\u003e \u003cp\u003eFigure 3 describes the time course, day by day, of PLT count as lower limit (10th centile) during the recovery period (after the nadir of PLT count). At day 9 from the nadir PLT count, 9 out of 10 patients reached the normal value of 150.000/mm\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFigure 4 shows the key time points of STEC-HUS from the beginning of abdominal symptoms, as observed in the 148 investigated patients with special regard to the time-course of PLT count.\u003c/p\u003e \u003cp\u003eIn particular, the nadir was reached on day 8. By day 14 half of the patients had normalized their PLT count and by day 25 all had normal PLT count.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe diagnosis of STEC-HUS is based on the classic diagnostic triad (platelet consumption, hemolysis, and kidney damage) in association with a STEC-proven gastrointestinal infection.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e On the contrary, atypical HUS is an exclusion diagnosis, if the mentioned triad is present and STEC infection and Thrombotic Thrombocytopenic Purpura (and few other ultrarare conditions) have been ruled out.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis nomenclature has been recently criticized, in favor of a classification more consistent with the advancement of knowledge in this area and based on the etiology of each entity.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Unfortunately, aHUS often complicates other conditions, such as infections, that may represent a trigger for complement disregulating abnormalities (genetic or acquired). Therefore, STEC infection, besides causing STEC-HUS may well trigger aHUS if the patient carries one or more of the mentioned abnormalities.\u003c/p\u003e \u003cp\u003eIndeed, variants in complement regulatory genes are not so rare and consequently STEC infections could occur in subjects at risk of developing aHUS as a consequence of the infection.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWhenever STEC infection and aHUS coexist in the same subject, a diagnostic dilemma is generated with potential serious consequences. In the described setting the differential diagnosis may be very challenging because all the laboratory parameters traditionally used for assessing TMA (haptoglobin, LDH, bilirubin, proteinuria, hematuria, thrombocytopenia, schistocytes, hemoglobin, etc.) will be indistinguishable in the two diseases.\u003c/p\u003e \u003cp\u003eHowever, while STEC-HUS is a self-limiting condition and the TMA is expected to spontaneously resolve within days, aHUS due to complement dysregulation, most commonly, does not resolve spontaneously and, if untreated, the majority of patients will require chronic dialysis due to the persisting microangiopathic process. \u003csup\u003e12\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe believe that the PLT count, better than any other biomarkers, can be useful to identify the coexistence of the 2 conditions by revealing an inconsistent time-course during recovery. The carefully monitoring platelet count during the recovery phase of STEC-related HUS may reveal a derangement from \u0026ldquo;normal\u0026rdquo; course that should raise suspicion of aHUS or of other conditions complicating STEC-HUS. namely superimposed infections or heparin-induced thrombocytopenia. All these conditions are associated with PLT consumption that will interfere with the recovery from STEC-HUS.\u003c/p\u003e \u003cp\u003eHowever, in order to identify a derangement from the natural course, a reference paradigm is needed and, to the best of our knowledge, such a paradigm is missing. The present paper is an attempt to provide reference values for PLT count in STEC-HUS based on data from 148 patients.\u003c/p\u003e \u003cp\u003eIn details, we underline that 100% of patients with STEC-HUS have reached a normal PLT count by day 14 from the nadir. Moreover, the 10th centile of PLT count day by day is provided as limit below which other diagnostic options should be considered.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion we offer clinicians a reference value of platelets count day by day as expected during the recovery phase of uncomplicated STEC-HUS to guide them in correctly evaluating the trend towards normalization that is expected in all patients within 14 days from the nadir value that is reached at a median of 8 days since the onset of symptoms.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHUS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHemolytic uremic syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaHUS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAtypical Hemolytic uremic syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSTEC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eShiga Toxin-producing Escherichia Coli\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThrombotic Micro-Angiopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCentral Nervous System\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePLT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePlatelet\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eAddress correspondence to\u003c/h2\u003e \u003cp\u003eDaniele Rossetti, Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Della Commenda 9, Milan, 20122, Italy ([email protected])\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding statement\u003c/h2\u003e \u003cp\u003eNo funding was provided to perform this study.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eWe wish to express our sincere gratitude to the following members of the ItalKid-HUS Network for their valuable collaboration and their commitment to the screening of patients presenting with acute bloody diarrhea:\u003c/p\u003e \u003cp\u003eFiorella Acquotta, Paolo Adamoli, Nicola Altamura, Angela Amoroso, Stefano Andreoni, Massimo Andreotti, Maddalena Antolini, Milana Arghittu, Francesca Atzeri, Carlo Baldioli, Barbara Balduzzi, Irene Benini, Simone Benvenuto, Francesco Beretta, Cristina Bertulli, Valeria Besutti, Lorenzo Biscardi, Annalisa Bonazza, Cristina Bonetti, Annalisa Bosco, Grazia Bossi, Marta Brambilla, Maria Francesca Brambillasca, Valentina Burzio, Anna Elisabetta Bussolini, Elena Cama, Patrizia Carlucci, Maria Carrabba, Maria Luisa Casciana, Daniela Casnaghi, Eleonora Castellone, Valeria Castorani, Marco Cazzaniga, Claudio Cavalli, Lisa Lucia Chenal, Rosaria Celano, Rossella Ceruti, Marta Cerutti, Giulia Cesano, Giulia Chiopris, Anna Cogliardi, Giacomo Colella, Lucia Collini, Rosaria Colombo, Dario Consonni, Crescenzo Coppola, Angela Corna, Annalisa Corti, Giorgia Daffunchio, Simona De Franco, Elena Lucia De Rose, Laura Dell\u0026rsquo;Era, Giulia Dilio, Clelia Di Mari, Sandra Esposito, Diana Fanti, Alessandra Ferrari, Ilaria Frugnoli, Maria Forestieri, Gloria Fumagalli, Maria Rita Gallina, Miriam Chiara Gatto, Claudio Giacomazzi, Stefano Grossi, Silvia Grosso, Chiara Gualeni, Elisa La Barba, Anna Maria La Pusata, Sara La Rosa, Annalisa Lastrico, Alberto Lepre, Francesca Lizzoli, Rosa Maria Maccarone, Anna Madera, Laura Martelli, Elena Mazzali, Elisabetta Mazzola, Marcella Mercuri, Elisa Milanesi, Chiara Minini, Paola Mirri, Sonia Monticone, Alice Monzani, Vincenza Morinello, Arianna Moroni, Maria Carmela Musolino, Maria Amata Negri, Stefano Nespoli, Bianca Osnaghi, Elisabetta Pagani, Franca Pagani, Cristina Partenope, Palmiro Pedroni, Giovanni Raimondo Pieri, Maria Antonietta Piscopo, Stefano Poli, Ilaria Possenti, Giulia Ramponi, Agrippino Reciputo, Barbara Roman, Barbara Ronchi, Chiara Rosazza, Elena Rossi, Claudia Ruggieri, Maria Lorena Ruzza, Filippo Salvini, Letizia Sardella, Martina Scali, Chiara Sciuto, Alessandra Scolari, Micaela Silvestri, Daniela Simoncini, Giulia Smylie, Rosa Maria Taibi, Francesca Tel, Sara Testa, Valentina Todescato, Elena Tommasoni, Paola Tommasi, Gaia Vanz\u0026ugrave;, Antonio Vergori, Federica Vianello, Chiara Vismara, Chiara Zambetti.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eData will be made available upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eArdissino G, Possenti I, Tel F, Testa S, Paglialonga F (2014) Time to change the definition of hemolytic uremic syndrome. \u003cem\u003eEuropean Journal of Internal Medicine\u003c/em\u003e vol. 25 Preprint at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ejim.2013.12.002\u003c/span\u003e\u003cspan address=\"10.1016/j.ejim.2013.12.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFakhouri F, Zuber J, Fr\u0026eacute;meaux-Bacchi V, Loirat C (2017) Haemolytic uraemic syndrome. \u003cem\u003eThe Lancet\u003c/em\u003e vol. 390 681\u0026ndash;696 Preprint at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(17)30062-4\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(17)30062-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAwofisayo-Okuyelu A, Brainard J, Hall I, McCarthy N (2019) Incubation Period of Shiga Toxin-Producing Escherichia coli. \u003cem\u003eEpidemiologic Reviews\u003c/em\u003e vol. 41 121\u0026ndash;129 Preprint at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/epirev/mxz001\u003c/span\u003e\u003cspan address=\"10.1093/epirev/mxz001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArdissino G et al (2021) Bloody Diarrhea and Shiga Toxin\u0026ndash;Producing Escherichia coli Hemolytic Uremic Syndrome in Children: Data from the ItalKid-HUS Network. J Pediatr 237\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichael M, Bagga A, Sartain SE, Smith RJH (2022) Haemolytic uraemic syndrome. \u003cem\u003eThe Lancet\u003c/em\u003e vol. 400 1722\u0026ndash;1740 Preprint at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0140-6736(22)01202-8\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(22)01202-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArdissino G et al (2016) Early volume expansion and outcomes of hemolytic uremic syndrome. Pediatrics 137\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTarr PI, Gordon CA, Chandler WL (2005) Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. in \u003cem\u003eLancet\u003c/em\u003e vol. 365 1073\u0026ndash;1086Elsevier B.V\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaleknia L et al (2025) Predicting Progression of STEC-HUS: Use of Shiga Toxin Subtype and Routine Laboratory Screening. J Pediatr Infect Dis Soc 14\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKavanagh D et al (2024) Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum. Kidney Int 106:1038\u0026ndash;1050\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNester CM et al (2024) An expert discussion on the atypical hemolytic uremic syndrome nomenclature\u0026mdash;identifying a road map to precision: a report of a National Kidney Foundation Working Group. Kidney Int 106:326\u0026ndash;336\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFr\u0026eacute;meaux-Bacchi V et al (2019) Complement gene variants and shiga toxin-producing escherichia coli-associated hemolytic uremic syndrome retrospective genetic and clinical study. Clin J Am Soc Nephrol 14:364\u0026ndash;377\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArdissino G et al (2024) Outcome of atypical hemolytic uremic syndrome: role of triggers and complement abnormalities in the response to C5 inhibition. J Nephrol 37:1017\u0026ndash;1026\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Platelets, HUS, STEC, TMA","lastPublishedDoi":"10.21203/rs.3.rs-8432171/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8432171/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHemolytic uremic syndrome (HUS) related to Shiga toxin-producing Escherichia Coli (STEC) infection is a severe, life-threatening thrombotic microangiopathy (TMA). Endothelial damage causes platelet consumption and consequently platelet count is a key biomarker for monitoring disease activity. The present paper describes the time course of platelet count in a cohort of patients with STEC-HUS in order to provide references helpful in identifying subjects who divert from the expected course because complications.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAll children treated at our Center with a well-established diagnosis of STEC-HUS during the period 2010\u0026ndash;2025 were retrospectively enrolled and platelets count was recorded until discharge. The nadir of platelets count for each patient was used to align the results and investigate the time course towards platelets normalization. The cumulative percentage of platelets normalization was calculated on daily basis, together with the 10th centile of platelets count.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003eDuring the 16 years under investigation, a total of 148 children were enrolled. The nadir of platelets count was 23,000/mm3 (IQR 14,000\u0026ndash;39,000) on day 8 since the beginning of symptoms. By day 14 from the nadir, 100% of patients had reached a platelets count\u0026thinsp;\u0026gt;\u0026thinsp;150.000/mm3.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eGiven that STEC-HUS is a self-limiting disease, the related TMA is expected to spontaneously cease within a defined time. If platelets count has a different course from the expected, the patient is likely to have complications that need to be actively searched for and treated accordingly (e.g. atypical HUS, disseminated intravascular coagulation or heparin induced thrombocytopenia).\u003c/p\u003e","manuscriptTitle":"Time-Course of Platelets Count in Children with Hemolytic Uremic Syndrome. Data from the ItalKid-HUS Network.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-20 12:22:10","doi":"10.21203/rs.3.rs-8432171/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2026-02-16T19:19:51+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2026-01-20T17:53:16+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-15T13:20:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-14T16:42:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2026-01-14T06:39:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9302c243-3dbd-4f34-abf2-723a68241cfc","owner":[],"postedDate":"January 20th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-10T12:56:20+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-20 12:22:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8432171","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8432171","identity":"rs-8432171","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}