{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:16:14Z","timestamp":1790820974590,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Policlinico Universitario Agostino Gemelli IRCCs","award":["Ricerca corrente 2022"],"award-info":[{"award-number":["Ricerca corrente 2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by a hereditary or immune-mediated deficiency of the enzyme ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). TTPs are caused by the following pathophysiological mechanisms: (1) the presence of inhibitory autoantibodies against ADAMTS13; and (2) hereditary mutations of the ADAMTS13 gene, which is present on chromosome 9. In both syndromes, TTP results from a severe deficiency of ADAMTS13, which is responsible for the impaired proteolytic processing of high-molecular-weight von Willebrand factor (HMW-VWF) multimers, which avidly interact with platelets and subendothelial collagen and promote tissue and multiorgan ischemia. Although the acute presentation of the occurring symptoms in acquired and hereditary TTPs is similar (microangiopathic hemolytic anemia, thrombocytopenia, and variable ischemic end-organ injury), their intensity, incidence, and precipitating factors are different, although, in both forms, a severe ADAMTS13 deficiency characterizes their physiopathology. This review is aimed at exploring the possible factors responsible for the different clinical and pathological features occurring in hereditary and immune-mediated TTPs.<\/jats:p>","DOI":"10.3390\/jcm12093111","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T02:06:35Z","timestamp":1682388395000},"page":"3111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immune and Hereditary Thrombotic Thrombocytopenic Purpura: Can ADAMTS13 Deficiency Alone Explain the Different Clinical Phenotypes?"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8090-9040","authenticated-orcid":false,"given":"Stefano","family":"Lancellotti","sequence":"first","affiliation":[{"name":"Servizio Malattie Emorragiche e Trombotiche, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2395-2691","authenticated-orcid":false,"given":"Monica","family":"Sacco","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia Traslazionale, Facolt\u00e0 di Medicina e Chirurgia \u201cAgostino Gemelli\u201d, Universit\u00e0 Cattolica S. Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8669-006X","authenticated-orcid":false,"given":"Maira","family":"Tardugno","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia Traslazionale, Facolt\u00e0 di Medicina e Chirurgia \u201cAgostino Gemelli\u201d, Universit\u00e0 Cattolica S. Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Ferretti","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia Traslazionale, Facolt\u00e0 di Medicina e Chirurgia \u201cAgostino Gemelli\u201d, Universit\u00e0 Cattolica S. Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-8849","authenticated-orcid":false,"given":"Raimondo","family":"De Cristofaro","sequence":"additional","affiliation":[{"name":"Servizio Malattie Emorragiche e Trombotiche, Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS, 00168 Roma, Italy"},{"name":"Dipartimento di Medicina e Chirurgia Traslazionale, Facolt\u00e0 di Medicina e Chirurgia \u201cAgostino Gemelli\u201d, Universit\u00e0 Cattolica S. Cuore, 00168 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/j.1752-8062.2009.00142.x","article-title":"Thrombotic microangiopathies: Multimers, metalloprotease, and beyond","volume":"2","author":"Moake","year":"2009","journal-title":"Clin. Transl. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Malgaj Vrecko, M., Ales Rigler, A., and Veceric-Haler, Z. (2022). Coronavirus Disease 2019-Associated Thrombotic Microangiopathy: Literature Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911307"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41059","DOI":"10.1074\/jbc.C100515200","article-title":"Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura","volume":"276","author":"Zheng","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/35097008","article-title":"Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura","volume":"413","author":"Levy","year":"2001","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1056\/NEJM199811263392202","article-title":"von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome","volume":"339","author":"Furlan","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1056\/NEJM199811263392203","article-title":"Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura","volume":"339","author":"Tsai","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11065","DOI":"10.1021\/bi0204692","article-title":"Processing of von Willebrand factor by ADAMTS-13","volume":"41","author":"Chung","year":"2002","journal-title":"Biochemistry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1056\/NEJMcp053024","article-title":"Clinical practice. Thrombotic thrombocytopenic purpura","volume":"354","author":"George","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1055\/s-0038-1669459","article-title":"Anti-ADAMTS13 Autoantibodies against Cryptic Epitopes in Immune-Mediated Thrombotic Thrombocytopenic Purpura","volume":"118","author":"Roose","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1097\/MOH.0000000000000602","article-title":"Insights into ADAMTS13 structure: Impact on thrombotic thrombocytopenic purpura diagnosis and management","volume":"27","author":"Roose","year":"2020","journal-title":"Curr. Opin. Hematol."},{"key":"ref_11","first-page":"353","article-title":"Open ADAMTS13, induced by antibodies, is a biomarker for subclinical immune-mediated thrombotic thrombocytopenic purpura","volume":"136","author":"Roose","year":"2020","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.blre.2009.11.001","article-title":"Inhibitory anti-ADAMTS 13 antibodies: Measurement and clinical application","volume":"24","author":"Scully","year":"2010","journal-title":"Blood Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1097\/CCM.0b013e31822e9d66","article-title":"Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Experience of the French Thrombotic Microangiopathies Reference Center","volume":"40","author":"Froissart","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1056\/NEJMoa1505533","article-title":"Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura","volume":"374","author":"Peyvandi","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1056\/NEJMoa1806311","article-title":"Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura","volume":"380","author":"Scully","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1515\/bmc-2019-0022","article-title":"Mechanochemistry of von Willebrand factor","volume":"10","author":"Lancellotti","year":"2019","journal-title":"Biomol. Concepts"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/S0006-3495(04)74136-3","article-title":"Hydrodynamic forces applied on intercellular bonds, soluble molecules, and cell-surface receptors","volume":"86","author":"Shankaran","year":"2004","journal-title":"Biophys. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1182\/blood-2003-05-1616","article-title":"Nonneutralizing IgM and IgG antibodies to von Willebrand factor-cleaving protease (ADAMTS-13) in a patient with thrombotic thrombocytopenic purpura","volume":"102","author":"Scheiflinger","year":"2003","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1111\/j.1538-7836.2006.02025.x","article-title":"Inhibitory autoantibodies against ADAMTS-13 in patients with thrombotic thrombocytopenic purpura bind ADAMTS-13 protease and may accelerate its clearance in vivo","volume":"4","author":"Shelat","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1182\/blood-2004-11-4490","article-title":"ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases","volume":"106","author":"Rieger","year":"2005","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.ebiom.2015.06.007","article-title":"Pathogenicity of Anti-ADAMTS13 Autoantibodies in Acquired Thrombotic Thrombocytopenic Purpura","volume":"2","author":"Thomas","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3232","DOI":"10.1182\/blood-2003-03-0908","article-title":"ADAMTS-13 cysteine-rich\/spacer domains are functionally essential for von Willebrand factor cleavage","volume":"102","author":"Soejima","year":"2003","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1160\/TH04-05-0301","article-title":"The spacer domain of ADAMTS13 contains a major binding site for antibodies in patients with thrombotic thrombocytopenic purpura","volume":"93","author":"Luken","year":"2005","journal-title":"Thromb. Haemost."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1160\/TH06-03-0135","article-title":"Amino acid regions 572-579 and 657-666 of the spacer domain of ADAMTS13 provide a common antigenic core required for binding of antibodies in patients with acquired TTP","volume":"96","author":"Luken","year":"2006","journal-title":"Thromb. Haemost."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/jth.15170","article-title":"Immunogenic hotspots in the spacer domain of ADAMTS13 in immune-mediated thrombotic thrombocytopenic purpura","volume":"19","author":"Roose","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/jth.13922","article-title":"An open conformation of ADAMTS-13 is a hallmark of acute acquired thrombotic thrombocytopenic purpura","volume":"16","author":"Roose","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1111\/jth.15332","article-title":"A human monoclonal antibody against the distal carboxyl terminus of ADAMTS-13 modulates its susceptibility to an inhibitor in thrombotic thrombocytopenic purpura","volume":"19","author":"Halkidis","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.1016\/S2352-3026(16)30018-7","article-title":"Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): A cross-sectional analysis of the French national registry for thrombotic microangiopathy","volume":"3","author":"Mariotte","year":"2016","journal-title":"Lancet Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1002\/pbc.24612","article-title":"Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: Comparison of incidence, demographic and clinical features","volume":"60","author":"Reese","year":"2013","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Martino, S., Jamme, M., Deligny, C., Busson, M., Loiseau, P., Azoulay, E., Galicier, L., Pene, F., Provot, F., and Dossier, A. (2016). Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156679"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.3324\/haematol.2016.151407","article-title":"Dissecting the pathophysiology of immune thrombotic thrombocytopenic purpura: Interplay between genes and environmental triggers","volume":"103","author":"Hrdinova","year":"2018","journal-title":"Haematologica"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/j.1538-7836.2010.03772.x","article-title":"HLA-DRB1*11: A strong risk factor for acquired severe ADAMTS13 deficiency-related idiopathic thrombotic thrombocytopenic purpura in Caucasians","volume":"8","author":"Coppo","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1538-7836.2009.03692.x","article-title":"Human leukocyte antigen association in idiopathic thrombotic thrombocytopenic purpura: Evidence for an immunogenetic link","volume":"8","author":"Scully","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mancini, I., Giacomini, E., Pontiggia, S., Artoni, A., Ferrari, B., Pappalardo, E., Gualtierotti, R., Trisolini, S.M., Capria, S., and Facchini, L. (2020). The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians. J. Clin. Med., 9.","DOI":"10.3390\/jcm9103379"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00277-011-1384-z","article-title":"The role of human leukocyte antigens as predisposing and\/or protective factors in patients with idiopathic thrombotic thrombocytopenic purpura","volume":"91","author":"John","year":"2012","journal-title":"Ann. Hematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1182\/blood.2020005395","article-title":"HLA loci predisposing to immune TTP in Japanese: Potential role of the shared ADAMTS13 peptide bound to different HLA-DR","volume":"135","author":"Sakai","year":"2020","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/j.1365-2141.2008.07107.x","article-title":"Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse","volume":"141","author":"Jin","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3324\/haematol.11739","article-title":"ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission","volume":"93","author":"Peyvandi","year":"2008","journal-title":"Haematologica"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1182\/blood-2016-06-724161","article-title":"Clinical importance of ADAMTS13 activity during remission in patients with acquired thrombotic thrombocytopenic purpura","volume":"128","author":"Page","year":"2016","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1182\/blood-2012-06-433235","article-title":"A second hit for TMA","volume":"120","author":"Miyata","year":"2012","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/j.1538-7836.2012.04674.x","article-title":"Complement activation in thrombotic thrombocytopenic purpura","volume":"10","author":"Reti","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1111\/bjh.16415","article-title":"Interrelationship between ADAMTS13 activity, von Willebrand factor, and complement activation in remission from immune-mediated trhrombotic thrombocytopenic purpura","volume":"189","author":"Wu","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1111\/jth.12369","article-title":"Complement activation and mortality during an acute episode of thrombotic thrombocytopenic purpura","volume":"11","author":"Wu","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.hoc.2015.01.008","article-title":"Ultralarge von Willebrand factor-induced platelet clumping and activation of the alternative complement pathway in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndromes","volume":"29","author":"Turner","year":"2015","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.4049\/jimmunol.1601121","article-title":"Interaction between Multimeric von Willebrand Factor and Complement: A Fresh Look to the Pathophysiology of Microvascular Thrombosis","volume":"199","author":"Bettoni","year":"2017","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Turner, N.A., and Moake, J. (2013). Assembly and activation of alternative complement components on endothelial cell-anchored ultra-large von Willebrand factor links complement and hemostasis-thrombosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059372"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Feng, S., Liang, X., Cruz, M.A., Vu, H., Zhou, Z., Pemmaraju, N., Dong, J.F., Kroll, M.H., and Afshar-Kharghan, V. (2013). The interaction between factor H and Von Willebrand factor. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073715"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1182\/blood-2014-06-585430","article-title":"von Willebrand factor is a cofactor in complement regulation","volume":"125","author":"Feng","year":"2015","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1182\/blood.2019001040","article-title":"Synergistic effects of ADAMTS13 deficiency and complement activation in pathogenesis of thrombotic microangiopathy","volume":"134","author":"Zheng","year":"2019","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/jca.21880","article-title":"Application of the French TMA Reference Center Score and the mortality in TTP Score in de novo and relapsed episodes of acquired thrombotic thrombocytopenic purpura at a tertiary care facility in Spain","volume":"36","year":"2021","journal-title":"J. Clin. Apher."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e12802","DOI":"10.1002\/rth2.12802","article-title":"Epidemiology, treatment patterns, clinical outcomes, and disease burden among patients with immune-mediated thrombotic thrombocytopenic purpura in the United States","volume":"6","author":"Adeyemi","year":"2022","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/jth.13186","article-title":"High prevalence of hereditary thrombotic thrombocytopenic purpura in central Norway: From clinical observation to evidence","volume":"14","author":"Waage","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.3324\/haematol.2019.216796","article-title":"The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: Key findings at enrollment until 2017","volume":"104","author":"Taleghani","year":"2019","journal-title":"Haematologica"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1160\/TH15-02-0119","article-title":"The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura. A clinical, biochemical and in silico study","volume":"115","author":"Lancellotti","year":"2016","journal-title":"Thromb. Haemost."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1182\/blood-2018-11-884700","article-title":"Characterization and treatment of congenital thrombotic thrombocytopenic purpura","volume":"133","author":"Alwan","year":"2019","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11902","DOI":"10.1073\/pnas.172277399","article-title":"Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity","volume":"99","author":"Kokame","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1182\/blood-2005-06-2482","article-title":"Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation","volume":"107","author":"Plaimauer","year":"2006","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1111\/j.1538-7836.2008.03109.x","article-title":"ADAMTS13 P475S polymorphism causes a lowered enzymatic activity and urea lability in vitro","volume":"6","author":"Akiyama","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1182\/blood-2018-01-827063","article-title":"A neonate presenting with jaundice, anemia, and thrombocytopenia","volume":"131","author":"Hager","year":"2018","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1182\/blood.2020009801","article-title":"Annual incidence and severity of acute episodes in hereditary thrombotic thrombocytopenic purpura","volume":"137","author":"Tarasco","year":"2021","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sukumar, S., Lammle, B., and Cataland, S.R. (2021). Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management. J. Clin. Med., 10.","DOI":"10.3390\/jcm10030536"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1111\/j.1538-7836.2009.03568.x","article-title":"IgG subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura","volume":"7","author":"Ferrari","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.3389\/fimmu.2018.01646","article-title":"Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura","volume":"9","author":"Sinkovits","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1182\/blood-2008-09-179754","article-title":"Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses","volume":"113","author":"Bruhns","year":"2009","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.3324\/haematol.2022.280651","article-title":"Immune thrombotic thrombocytopenic purpura plasmas induce calcium- and IgG-dependent endothelial activation: Correlations with disease severity","volume":"108","author":"Tellier","year":"2023","journal-title":"Haematologica"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6280","DOI":"10.1073\/pnas.1814797116","article-title":"P-selectin drives complement attack on endothelium during intravascular hemolysis in TLR-4\/heme-dependent manner","volume":"116","author":"Merle","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1182\/blood-2013-03-489245","article-title":"Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome","volume":"122","author":"Frimat","year":"2013","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Cauchois, R., Muller, R., Lagarde, M., Dignat-George, F., Tellier, E., and Kaplanski, G. (2023). Is Endothelial Activation a Critical Event in Thrombotic Thrombocytopenic Purpura?. J. Clin. Med., 12.","DOI":"10.3390\/jcm12030758"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0049-3848(98)00151-0","article-title":"Plasma from a patient with thrombotic thrombocytopenic purpura induces endothelial cell apoptosis and platelet aggregation","volume":"93","author":"Wu","year":"1999","journal-title":"Thromb. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1046\/j.1365-2141.2001.02516.x","article-title":"Elevated endothelial microparticles in thrombotic thrombocytopenic purpura: Findings from brain and renal microvascular cell culture and patients with active disease","volume":"112","author":"Jimenez","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1111\/jth.12681","article-title":"Circulating endothelial cells and progenitors as prognostic factors during autoimmune thrombotic thrombocytopenic purpura: Results of a prospective multicenter French study","volume":"12","author":"Widemann","year":"2014","journal-title":"J. Thromb. Haemost."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1182\/blood-2010-04-280479","article-title":"Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus)","volume":"116","author":"Feys","year":"2010","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1002\/cphy.c180034","article-title":"Transient Receptor Potential Channels and Endothelial Cell Calcium Signaling","volume":"9","author":"Thakore","year":"2019","journal-title":"Compr. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev.pharmtox.48.113006.094928","article-title":"The TRPC class of ion channels: A critical review of their roles in slow, sustained increases in intracellular Ca2+ concentrations","volume":"49","author":"Birnbaumer","year":"2009","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s00418-004-0720-y","article-title":"Expression of TRPC homologs in endothelial cells and smooth muscle layers of human arteries","volume":"122","author":"Yip","year":"2004","journal-title":"Histochem. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e29992","DOI":"10.1002\/pbc.29992","article-title":"Clinical features and neurological outcomes in pediatric immune-mediated thrombotic thrombocytopenic purpura: A report from a large pediatric hematology center","volume":"69","author":"Graciaa","year":"2022","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1182\/blood-2017-06-788026","article-title":"Recombinant ADAMTS-13: First-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura","volume":"130","author":"Scully","year":"2017","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"E420","DOI":"10.1002\/ajh.26693","article-title":"Caplacizumab for congenital thrombotic thrombocytopenic purpura","volume":"97","author":"Boothby","year":"2022","journal-title":"Am. J. 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