Caplacizumab in a Case of Very Late Diagnosis of Congenital Thrombotic Thrombocytopenic Purpura

Caplacizumab in a Case of Very Late Diagnosis of Congenital Thrombotic Thrombocytopenic Purpura | 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 Case Report Caplacizumab in a Case of Very Late Diagnosis of Congenital Thrombotic Thrombocytopenic Purpura Elisa Quinti, Laura Fasano, Chiara Lucarelli, Valentina Carrai, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7435341/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombotic microangiopathy caused by inherited deficiency of ADAMTS13. This enzymatic defect results in the accumulation of ultra-large VWF multimers, predisposing to microvascular thrombosis. Clinical presentation usually occurs in neonatal period or childhood, more rarely in adults, especially during pregnancy. Treatment involves support with fresh frozen plasma transfusions to normalize ADAMTS13 levels. Caplacizumab, an anti-VWF antibody, is approved for the treatment of acquired TTP and the use in congenital forms should be considered off-label in selected cases with severe clinical manifestations. In this case, we describe our experience with Caplaczumab, highlighting its therapeutic potential in congenital forms for rapid clinical and hematological improvement, reducing both the number of plasmapheresis sessions and the length of stay in intensive care. Although off-label, Caplacizumab may represent a valuable option in selected cTTP patients with severe manifestations or refractory to the standard procedures. Further studies to define its role in congenital TTP management are warranted. Congenital thrombotic thrombocytopenic purpura ADAMTS13 Caplaczumab case report Figures Figure 1 Introduction Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombotic microangiopathy caused by an inherited deficiency of the von Willebrand factor (VWF)-cleaving metalloproteinase ADAMTS13. This deficiency leads to the presence of abnormal ultra-large VWF multimers, which are presumed to contribute to the subsequent development of immune thrombotic thrombocytopenic purpura (TTP). Disease-causing mutations occur throughout the ADAMTS13 gene, located on chromosome 9q34, with over 150 mutations described to date. (1) Microangiopathic Haemolytic Anemia (MAHA) is the diagnostic presentation in 90% of patients with the remaining patients being diagnosed following investigation for thrombocytopenia. The timing of the first manifestation can be variable: most males present with the disease in the neonatal period or in childhood, while in females it usually occurs during pregnancy. In very few cases of less severe forms we may have late-onset symptoms and diagnosis, even after 70 years of age. In this context, clinical histories have reported recurrence of symptoms such as thrombocytopenia or anemia during the disease or pregnancy, or obstetric complications, or vascular events such as early TIA or stroke, and previous diagnosis of conditions such as chronic immune thrombocytopenic purpura, immune-mediated TTP or Evans syndrome. Late recognition of cTTP and delay in treatment may result in adverse outcomes(1). The mainstay of treatment for cTTP focuses on restoring ADAMTS13 levels, typically through plasma infusions as regular prophylactic support or on-demand treatment based on clinical features. Caplacizumab, an anti-von Willebrand factor antibody, is approved for the treatment of acquired TTP. No studies have been conducted evaluating the efficacy of caplacizumab in the treatment of cTTP, and patients with cTTP were excluded from registration studies (2). The use of caplacizumab in the treatment of thrombotic thrombocytopenic purpura should be considered off-label in selected cases with severe clinical manifestations. Our center has recently managed a patient with recurrent cTTP using caplacizumab as in autoimmune forms Case Presentation In August 2024, a 74-year-old woman presented to the Emergency Department with acute onset of dysarthria, right-sided facial deficit and Mingazzini I positivity, indicative of an acute neurological event. Her medical history included a previous ischemic stroke in January 2019 (with normal platelet count) and recurrent pregnancy loss, with thrombophilia testing ruling out inherited prothrombotic conditions (except for mild anti-cardiolipin antibody positivity). A non-contrast CT scan documented an ischemic infarction in the middle cerebral artery territory. Laboratory investigations revealed thrombocytopenia (platelet count 66 × 10³/µL), normal coagulation parameters, elevated lactate dehydrogenase (LDH 585 U/L), normal hemoglobin levels (12.7 g/dL) and white blood cell count, normal total bilirubin (1.1 mg/dl) and preserved renal function (creatinine: 1.12 mg/dL). Given the thrombocytopenia, corticosteroid therapy (methylprednisolone 1 mg/kg) was started. Initially, the cerebral ischemia was suspected to be secondary to septic endocarditis due to the detection of valvular abnormalities on echocardiography. Consequently, empirical antibiotic therapy was initiated but later discontinued after a PET scan ruled out an ongoing infectious process. Given the suspicion of thrombotic thrombocytopenic purpura (TTP), additional laboratory tests were performed. Peripheral blood smear analysis revealed the presence of schistocytes (5%), along with evidence of hemolysis, including reduced haptoglobin (<30 mg/dL) and further elevation of LDH (893 U/L), negative direct coomb and ADAMTS13 activity was suppressed. Based on these findings, the patient was promptly transferred to the intensive care unit (ICU) for initiation of Caplacizumab (10 mg) and therapeutic plasma exchange. After four days, the patient demonstrated a full recovery of platelet count (375 x 10³/µL) and improvement in hemolysis markers (Figure 1), leading to discontinuation of PEX. Meanwhile, repeated testing showed that ADAMTS13 inhibitor levels remained within normal limits, whereas ADAMTS13 activity started to increase, but below 10%. Suspecting refractory disease, therapy was supplemented with four weekly infusions of Rituximab (375 mg/m²). Despite this, hemolysis markers (LDH, bilirubin, and haptoglobin) continued to show an improving trend, platelet counts remained within the normal range, but ADAMTS13 activity was 1.7%. Given the patient’s clinical history, extensive autoimmunity and coagulation studies were performed, including ANA, ENA, ANCA, lupus anticoagulant (LAC), anti-phospholipid antibodies, and genetic testing for F2 (prothrombin gene mutation) and F5 Leiden , protein C, protein S and activated protein C resistance. All results were negative. Consequently, screening for a congenital form of TTP was pursued by Next Generation Sequencing and unexpectedly two variants were detected: c.1883A>G; p.(Tyr628Cys) and c.3251G>A;p.(Cys1084Tyr). The first variant was still not described in literature, the second one was associated with cTTP. According to the recommendation for the management of congenital form (3) caplacizumab was stopped and fresh frozen plasma administration was started as a source of ADAMTS13 activity. Unfortunately, following the first administration, the patient developed severe pneumonia, which triggered a re-exacerbation of the TMA, ultimately proving fatal for respiratory distress. First of all, in the clinical case described we had an unusual very late recognition of cTTP with a consequent delayed diagnosis. As frequently reported in the literature, the patient had been diagnosed with chronic immune thrombocytopenic purpura for many years, and experienced several ischemic hits and relative serious sequelae. Caplacizumab has proven effective in adults as add-on therapy for aTTP (4, 5), without indication in the setting of congenital forms. To our knowledge, only a case of cTTP successfully treated with caplacizumab has been reported (6). Even in our experience, the use of caplacizumab associated with PEX determined a rapid haematological response, allowing procedures to stop without any significant adverse events. It appears that caplacizumab may present a valuable therapeutic option even in the setting of cTTP, maybe assuming only a short administration period to achieve a complete hematological response, especially in those cases refractory to therapy and where the risk of volume overload is significant. Recombinant ADAMTS13 may eventually becomes the principal strategy for the treatment of cTTP (7), but we could expect that some patients, as described in haemophilia (8), develop anti-ADAMTS13 alloantibodies. In this context of high risk of clinical relapses a bypass strategy could be indicated and caplacizumab, despite limited evidence on efficacy and safety in cTTP, has an important therapeutic potential even in this setting. Declarations Ethics approval and consent to participate : The study was conducted in accordance with the Declaration of Helsinki. Ethics review and approval for this study have been suspended because it involves a single clinical case without a formal analysis to evaluate the efficacy of a therapeutic approach. Consent for publication : Written informed consent for publication has been acquired from the patients whose picture is described in this report. Funding : This research received no external funding. Author Contribution Conceptualization, methodology, patient management, case reporting and writing - original draft preparation, E.Q., B.S.; methodology, patient managemen and writing L.F., C.L., C. V., F.F., A.A., I.M. ; writing—review and editing A.M.V. References Alwan F, Vendramin C, Liesner R, Clark A, Lester W, Dutt T, Thomas W, Gooding R, Biss T, Watson HG, Cooper N, Rayment R, Cranfield T, van Veen JJ, Hill QA, Davis S, Motwani J, Bhatnagar N, Priddee N, David M, Crowley MP, Alamelu J, Lyall H, Westwood JP, Thomas M, Scully M. Characterization and treatment of congenital thrombotic thrombocytopenic purpura. Ann Hematol. [Forthcoming]. European Medicines Agency. European Public Assessment Report: Cablivi. [Internet]. [cited 2025 May 24]. Available from: https://www.ema.europa.eu/en/documents/assessment-report/cablivi-epar-public-assessment-report_en.pdf Zheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, Matsumoto M, Mustafa RA, Pai M, Rock G, Russell L, Tarawneh R, Valdes J, Peyvandi F. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496–2502. Scully M, Cataland SR, Peyvandi F, et al; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335–346. Peyvandi F, Cataland S, Scully M, Coppo P, Knoebl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Minkue Mi Edou J, De Winter H, Callewaert F. Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis. Blood Adv. 2021;5(8):2137–2141. Boobthy A, Mazepa M. Caplacizumab for congenital thrombotic thrombocytopenic purpura. Am J Hematol. 2022;97(11):E420–E421. Scully M, Knöbl P, Kentouche K, Rice L, Windyga J, Schneppenheim R, Kremer Hovinga JA, Kajiwara M, Fujimura Y, Maggiore C, Doralt J, Hibbard C, Martell L, Ewenstein B. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017;130(19):2055–2063. Peyvandi F, Mannucci PM, Garagiola I, El-Beshlawy A, Elalfy M, Ramanan V, Eshghi P, Hanagavadi S, Varadarajan R, Karimi M, et al. A randomized trial of factor VIII and neutralizing antibodies in hemophilia A. N Engl J Med. 2016;374:2054–2064. Additional Declarations No competing interests reported. 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-7435341","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":523918954,"identity":"012ba872-c5b2-4307-a357-27abba397d3a","order_by":0,"name":"Elisa 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11:37:50","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":39263,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7435341/v1/bfc4eb7fe2f652d744aea6d5.html"},{"id":92801115,"identity":"16aa2bc4-dead-4769-acf6-17e3e3e57341","added_by":"auto","created_at":"2025-10-05 11:37:50","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":239692,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical overview of laboratory parameters across treatment days with combined PEX and Caplacizumab therapy\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7435341/v1/4b3c9d7cd64d79c8ba570e22.jpeg"},{"id":108180982,"identity":"b75fc36e-f043-497a-88c6-d0757a5c0fe9","added_by":"auto","created_at":"2026-04-30 08:55:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":351251,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7435341/v1/5aea3bb3-8d04-40a8-af88-e700b71348ef.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eCaplacizumab in a Case of Very Late Diagnosis of Congenital Thrombotic Thrombocytopenic Purpura \u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCongenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombotic microangiopathy caused by an inherited deficiency of the von Willebrand factor (VWF)-cleaving metalloproteinase ADAMTS13. This deficiency leads to the presence of abnormal ultra-large VWF multimers, which are presumed to contribute to the subsequent development of immune thrombotic thrombocytopenic purpura (TTP). Disease-causing mutations occur throughout the ADAMTS13 gene, located on chromosome 9q34, with over 150 mutations described to date. (1)\u003c/p\u003e\n\u003cp\u003eMicroangiopathic Haemolytic Anemia (MAHA) is \u0026nbsp;the diagnostic presentation in 90% of patients \u0026nbsp;with the remaining patients being diagnosed following investigation for thrombocytopenia.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe timing of the first manifestation can be variable: most males present with the disease in the neonatal period or in childhood, while in females it usually occurs during pregnancy. In very few cases of less severe forms we may have late-onset symptoms and diagnosis, even after 70 years of age.\u003c/p\u003e\n\u003cp\u003eIn this context, clinical histories have reported recurrence of symptoms such as thrombocytopenia or anemia during the disease or pregnancy, or obstetric complications, or vascular events such as early TIA or stroke, and previous diagnosis of conditions such as chronic immune thrombocytopenic purpura, immune-mediated TTP or Evans syndrome. Late recognition of cTTP and delay in treatment may result in \u0026nbsp;adverse outcomes(1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mainstay of treatment for cTTP focuses on restoring ADAMTS13 levels, typically through plasma infusions as regular prophylactic support or on-demand treatment based on clinical features. Caplacizumab, an anti-von Willebrand factor antibody, is approved for the treatment of acquired TTP. No studies have been conducted evaluating the efficacy of caplacizumab in the treatment of cTTP, and patients with cTTP were excluded from registration studies (2). The use of caplacizumab in the treatment of thrombotic thrombocytopenic purpura should be considered off-label in selected cases with severe clinical manifestations. Our center has recently managed a patient with recurrent cTTP using caplacizumab as in autoimmune forms\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eIn August 2024, a 74-year-old woman presented to the Emergency Department with acute onset of dysarthria, right-sided facial deficit and Mingazzini I positivity, indicative of an acute neurological event. Her medical history included a previous ischemic stroke in January 2019 (with normal platelet count) and recurrent pregnancy loss, with thrombophilia testing ruling out inherited prothrombotic conditions (except for mild anti-cardiolipin antibody positivity). A non-contrast CT scan documented an ischemic infarction in the middle cerebral artery territory.\u003c/p\u003e\n\u003cp\u003eLaboratory investigations revealed thrombocytopenia (platelet count 66 × 10³/µL), normal coagulation parameters, elevated lactate dehydrogenase (LDH 585 U/L), normal hemoglobin levels (12.7 g/dL) and white blood cell count, normal total bilirubin (1.1 mg/dl) and preserved renal function (creatinine: 1.12 mg/dL). Given the thrombocytopenia, corticosteroid therapy (methylprednisolone 1 mg/kg) was started.\u003c/p\u003e\n\u003cp\u003eInitially, the cerebral ischemia was suspected to be secondary to septic endocarditis due to the detection of valvular abnormalities on echocardiography. Consequently, empirical antibiotic therapy was initiated but later discontinued after a PET scan ruled out an ongoing infectious process.\u003c/p\u003e\n\u003cp\u003eGiven the suspicion of thrombotic thrombocytopenic purpura (TTP), additional laboratory tests were performed. Peripheral blood smear analysis revealed the presence of schistocytes (5%), along with evidence of hemolysis, including reduced haptoglobin (\u0026lt;30 mg/dL) and further elevation of LDH (893 U/L), negative direct coomb and ADAMTS13 activity was suppressed. Based on these findings, the patient was promptly transferred to the intensive care unit (ICU) for initiation of Caplacizumab (10 mg) and therapeutic plasma exchange.\u003c/p\u003e\n\u003cp\u003eAfter four days, the patient demonstrated a full recovery of platelet count (375 x 10³/µL) and improvement in hemolysis markers (Figure 1), leading to discontinuation of PEX. Meanwhile, repeated testing showed that ADAMTS13 inhibitor levels remained within normal limits, whereas ADAMTS13 activity started to increase, but below 10%. Suspecting refractory disease, therapy was supplemented with four weekly infusions of Rituximab (375 mg/m²). Despite this, hemolysis markers (LDH, bilirubin, and haptoglobin) continued to show an improving trend, platelet counts remained within the normal range, but ADAMTS13 activity was 1.7%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGiven the patient’s clinical history, extensive autoimmunity and coagulation studies were performed, including ANA, ENA, ANCA, lupus anticoagulant (LAC), anti-phospholipid antibodies, and genetic testing for \u003cem\u003eF2\u003c/em\u003e (prothrombin gene mutation) and \u003cem\u003eF5 Leiden\u003c/em\u003e, protein C, protein S and activated protein C resistance. All results were negative. Consequently, screening for a congenital form of TTP was pursued by Next Generation Sequencing and unexpectedly two variants were detected: c.1883A\u0026gt;G; p.(Tyr628Cys) and c.3251G\u0026gt;A;p.(Cys1084Tyr). The first variant was still not described in literature, the second one was associated with cTTP.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccording to the recommendation for the management of congenital form (3) caplacizumab was stopped and fresh frozen plasma administration was started as a source of ADAMTS13 activity. Unfortunately, following the first administration, the patient developed severe pneumonia, which triggered a re-exacerbation of the TMA, ultimately proving fatal for respiratory distress.\u003c/p\u003e\n\u003cp\u003eFirst of all, in the clinical case described we had an unusual very late recognition of cTTP with a consequent delayed diagnosis. As frequently reported in the literature, the patient had been \u0026nbsp;diagnosed with chronic immune thrombocytopenic purpura for many years, and experienced several ischemic hits and relative \u0026nbsp; serious sequelae.\u003c/p\u003e\n\u003cp\u003eCaplacizumab has proven effective in adults as add-on therapy for aTTP (4, 5), without indication in the setting of congenital forms.\u003c/p\u003e\n\u003cp\u003eTo our knowledge, only a case of cTTP successfully treated \u0026nbsp;with caplacizumab has been reported (6).\u003c/p\u003e\n\u003cp\u003eEven in our experience, the use of caplacizumab associated with PEX determined a rapid haematological response, allowing procedures to stop without any significant adverse events. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIt appears that caplacizumab may present a valuable therapeutic option even in the setting of cTTP, maybe assuming only a short administration period to achieve a complete hematological response, especially in those cases refractory to therapy and where the risk of volume overload is significant. Recombinant ADAMTS13 may eventually becomes the principal strategy for the treatment of cTTP (7), but we could expect that some patients, as described \u0026nbsp;in haemophilia (8), \u0026nbsp;develop anti-ADAMTS13 alloantibodies. In this context of high risk of clinical relapses a bypass strategy could be indicated and caplacizumab, despite limited evidence on efficacy and safety in cTTP, has \u0026nbsp;an important therapeutic potential even in this setting.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e: The study was conducted in accordance with the\u003cbr\u003e\u0026nbsp;Declaration of Helsinki. Ethics review and approval for this study have been suspended because it involves a single clinical case without a formal analysis to evaluate the efficacy of a therapeutic approach.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e: Written informed consent for publication has been acquired from the patients whose picture is described in this report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e: This research received no external funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization, methodology, patient management, case reporting and writing - original draft preparation, E.Q., B.S.; methodology, patient managemen and writing L.F., C.L., C. V., F.F., A.A., I.M. ; writing\u0026mdash;review and editing A.M.V.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAlwan F, Vendramin C, Liesner R, Clark A, Lester W, Dutt T, Thomas W, Gooding R, Biss T, Watson HG, Cooper N, Rayment R, Cranfield T, van Veen JJ, Hill QA, Davis S, Motwani J, Bhatnagar N, Priddee N, David M, Crowley MP, Alamelu J, Lyall H, Westwood JP, Thomas M, Scully M. Characterization and treatment of congenital thrombotic thrombocytopenic purpura. Ann Hematol. [Forthcoming].\u003c/li\u003e\n\u003cli\u003eEuropean Medicines Agency. European Public Assessment Report: Cablivi. [Internet]. [cited 2025 May 24]. Available from: https://www.ema.europa.eu/en/documents/assessment-report/cablivi-epar-public-assessment-report_en.pdf\u003c/li\u003e\n\u003cli\u003eZheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, Matsumoto M, Mustafa RA, Pai M, Rock G, Russell L, Tarawneh R, Valdes J, Peyvandi F. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496\u0026ndash;2502.\u003c/li\u003e\n\u003cli\u003eScully M, Cataland SR, Peyvandi F, et al; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335\u0026ndash;346.\u003c/li\u003e\n\u003cli\u003ePeyvandi F, Cataland S, Scully M, Coppo P, Knoebl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Minkue Mi Edou J, De Winter H, Callewaert F. Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis. Blood Adv. 2021;5(8):2137\u0026ndash;2141.\u003c/li\u003e\n\u003cli\u003eBoobthy A, Mazepa M. Caplacizumab for congenital thrombotic thrombocytopenic purpura. Am J Hematol. 2022;97(11):E420\u0026ndash;E421.\u003c/li\u003e\n\u003cli\u003eScully M, Kn\u0026ouml;bl P, Kentouche K, Rice L, Windyga J, Schneppenheim R, Kremer Hovinga JA, Kajiwara M, Fujimura Y, Maggiore C, Doralt J, Hibbard C, Martell L, Ewenstein B. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017;130(19):2055\u0026ndash;2063.\u003c/li\u003e\n\u003cli\u003ePeyvandi F, Mannucci PM, Garagiola I, El-Beshlawy A, Elalfy M, Ramanan V, Eshghi P, Hanagavadi S, Varadarajan R, Karimi M, et al. A randomized trial of factor VIII and neutralizing antibodies in hemophilia A. N Engl J Med. 2016;374:2054\u0026ndash;2064.\u003c/li\u003e\n\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":"Congenital thrombotic thrombocytopenic purpura, ADAMTS13, Caplaczumab, case report","lastPublishedDoi":"10.21203/rs.3.rs-7435341/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7435341/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCongenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombotic microangiopathy caused by inherited deficiency of ADAMTS13. This enzymatic defect results in the accumulation of ultra-large VWF multimers, predisposing to microvascular thrombosis. Clinical presentation usually occurs in neonatal period or childhood, more rarely in adults, especially during pregnancy. \u003cbr\u003e\nTreatment involves support with fresh frozen plasma transfusions to normalize ADAMTS13 levels. Caplacizumab, an anti-VWF antibody, is approved for the treatment of acquired TTP and the use in congenital forms should be considered off-label in selected cases with severe clinical manifestations. \u003cbr\u003e\n In this case, we describe our experience with Caplaczumab, highlighting its therapeutic potential in congenital forms for rapid clinical and hematological improvement, reducing both the number of plasmapheresis sessions and the length of stay in intensive care. Although off-label, Caplacizumab may represent a valuable option in selected cTTP patients with severe manifestations or refractory to the standard procedures. Further studies to define its role in congenital TTP management are warranted.\u003c/p\u003e","manuscriptTitle":"Caplacizumab in a Case of Very Late Diagnosis of Congenital Thrombotic Thrombocytopenic Purpura","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-05 11:37:45","doi":"10.21203/rs.3.rs-7435341/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":"1d65705d-906f-498f-888c-091efa1b7b29","owner":[],"postedDate":"October 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-25T06:10:39+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-05 11:37:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7435341","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7435341","identity":"rs-7435341","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}