Should we consider caplacizumab as routine treatment for acute thrombotic thrombocytopenic purpura? An expert perspective on the pros and cons

References

• Gómez-Seguí I, Pascual Izquierdo C, Mingot Castellano ME, et al. An update on the pathogenesis and diagnosis of thrombotic thrombocytopenic purpura. Expert Rev Hematol. 2023;16(1):17–32. doi: 10.1080/17474086.2023.2159803
   PubMed Web of Science ®Google Scholar
• Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian apheresis study group. N Engl J Med. 1991;325(6):393–397. doi: 10.1056/NEJM199108083250604
   PubMed Web of Science ®Google Scholar
• Staley EM, Cao W, Pham HP, et al. Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpura. Haematologica. 2019;104(1):166–175. doi: 10.3324/haematol.2018.198275
   PubMed Web of Science ®Google Scholar
• Goel R, King KE, Takemoto CM, et al. Prognostic risk-stratified score for predicting mortality in hospitalized patients with thrombotic thrombocytopenic purpura: nationally representative data from 2007 to 2012. Transfusion. 2016;56(6):1451–1458. doi: 10.1111/trf.13586
   PubMed Web of Science ®Google Scholar
• Balasubramaniyam N, Kolte D, Palaniswamy C, et al. Predictors of in-hospital mortality and acute myocardial infarction in thrombotic thrombocytopenic purpura. Am J Med. 2013;126(11):1016.e1–1017. doi: 10.1016/j.amjmed.2013.03.021
   PubMed Web of Science ®Google Scholar
• Zheng L, Zheng XL. How should caplacizumab be used for treatment of immune thrombotic thrombocytopenic purpura? Ann Blood. 2023;8:11. doi: 10.21037/aob-21-87
   PubMedGoogle Scholar
• Sukumar S, Lämmle B, Cataland SR. Thrombotic Thrombocytopenic Purpura: pathophysiology, diagnosis, and management. J Clin Med. 2021;10(3):536. doi: 10.3390/jcm10030536
   PubMed Web of Science ®Google Scholar
• Gómez-Seguí I, Pascual Izquierdo C, de la Rubia Comos J. Best practices and recommendations for drug regimens and plasma exchange for immune thrombotic thrombocytopenic purpura. Expert Rev Hematol. 2021 Aug;14(8):707–719. doi: 10.1080/17474086.2021.1956898
   PubMed Web of Science ®Google Scholar
• Westwood JP, Thomas M, Alwan F, et al. Rituximab prophylaxis to prevent thrombotic thrombocytopenic purpura relapse: outcome and evaluation of dosing regimens. Blood Adv. 2017;1(15):1159–1166. doi: 10.1182/bloodadvances.2017008268
   PubMed Web of Science ®Google Scholar
• Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020;18(10):2496–2502. doi: 10.1111/jth.15010
   PubMed Web of Science ®Google Scholar
• Mingot ME, Pascual C, González A, et al. Recommendations for the diagnosis and treatment of patients with thrombotic thrombocytopenic purpura. Med Clin. 2022;158(12):.e630.1–.e630.14. doi: 10.1016/j.medcle.2021.03.038
   Web of Science ®Google Scholar
• Sargentini-Maier ML, De Decker P, Tersteeg C, et al. Clinical pharmacology of caplacizumab for the treatment of patients with acquired thrombotic thrombocytopenic purpura. Expert Rev Clin Pharmacol. 2019;12(6):537–545. doi: 10.1080/17512433.2019.1607293
   PubMed Web of Science ®Google Scholar
• Elverdi T, Eskazan AE. Caplacizumab as an emerging treatment option for acquired thrombotic thrombocytopenic purpura. Drug Des Devel Ther. 2019;13:1251–1258. doi: 10.2147/DDDT.S134470
   PubMed Web of Science ®Google Scholar
• Zheng X, Chung D, Takayama TK, et al. Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem. 2001;276(44):41059–41063. doi: 10.1074/jbc.C100515200
   PubMed Web of Science ®Google Scholar
• Duggan S. Caplacizumab: First Global Approval. Drugs. 2018 Oct;78(15):1639–1642. doi: 10.1007/s40265-018-0989-0
   PubMed Web of Science ®Google Scholar
• Lee HT, Park UB, Jeong TJ, et al. High-resolution structure of the vWF A1 domain in complex with caplacizumab, the first nanobody-based medicine for treating acquired TTP. Biochem Biophys Res Commun. 2021;567:49–55. doi: 10.1016/j.bbrc.2021.06.030
   PubMed Web of Science ®Google Scholar
• TITAN Investigators, Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016;374(6):511–522.
   PubMed Web of Science ®Google Scholar
• HERCULES Investigators, Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019;380(4):335–346.
   PubMed Web of Science ®Google Scholar
• Peyvandi F, Cataland S, Scully M, et al. Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis. Blood Adv. 2021;5(8):2137–2141. doi: 10.1182/bloodadvances.2020001834
   PubMed Web of Science ®Google Scholar
• Coppo P, Bubenheim M, Azoulay E, et al. A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP. Blood. 2021;137(6):733–742. doi: 10.1182/blood.2020008021
   PubMedGoogle Scholar
• Völker LA, Kaufeld J, Miesbach W, et al. Real-world data confirm the effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura. Blood Adv. 2020 Jul 14;4(13):3085–3092. doi: 10.1182/bloodadvances.2020001973
   PubMed Web of Science ®Google Scholar
• Dutt T, Shaw RJ, Stubbs M, et al. Real-world experience with caplacizumab in the management of acute TTP. Blood. 2021 Apr 1;137(13):1731–1740. doi: 10.1182/blood.2020007599
   PubMed Web of Science ®Google Scholar
• Sanofi. [cited 2021 Jan 12]. Availble from: https://www.ema.europa.eu/en/medicines/human/EPAR/cablivi
   Google Scholar
• Sanofi: FDA approves Cablivi® (caplacizumab-yhdp), the first Nanobody®-based medicine, for adults with acquired thrombotic thrombocytopenic purpura (aTTP) - Sanofi. [cited 2021 Jan 12]. Availbale from: https://www.sanofi.com/en/media-room/pressreleases/2019/2019-02-06-17-43-21
   Google Scholar
• Zheng XL. The standard of care for immune thrombotic thrombocytopenic purpura today. J Thromb Haemost. 2021;19(8):1864–1871. doi: 10.1111/jth.15406
   PubMed Web of Science ®Google Scholar
• Izquierdo CP, Mingot-Castellano ME, Fuentes AEK, et al. Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura. Blood Adv. 2022;6(24):6219–6227. doi: 10.1182/bloodadvances.2022008028
   PubMed Web of Science ®Google Scholar
• German TTP-Study Group, Völker LA, Kaufeld J, Balduin G, et al. Impact of first-line use of caplacizumab on treatment outcomes in immune thrombotic thrombocytopenic purpura. J Thromb Haemost. 2023;21(3):559–572.
   PubMed Web of Science ®Google Scholar
• Völker LA, Brinkkoetter PT, Cataland SR, et al. Five years of caplacizumab - lessons learned and remaining controversies in immune-mediated thrombotic thrombocytopenic purpura. J Thromb Haemost. 2023;21(10):2718–2725. doi: 10.1016/j.jtha.2023.07.027
   PubMed Web of Science ®Google Scholar
• Goshua G, Sinha P, Hendrickson JE, et al. Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura. Blood. 2021;137(7):969–976. doi: 10.1182/blood.2020006052
   PubMed Web of Science ®Google Scholar
• Butt A, Allen C, Purcell A, et al. Global health resource utilization and cost-effectiveness of therapeutics and diagnostics in immune thrombotic Thrombocytopenic Purpura (TTP). J Clin Med. 2023 Jul 25;12(15):4887. doi: 10.3390/jcm12154887
   PubMed Web of Science ®Google Scholar
• Djulbegovic M, Tong J, Xu A, et al. Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis. Blood Adv. 2023;7(10):2132–2142. doi: 10.1182/bloodadvances.2022008443
   PubMed Web of Science ®Google Scholar
• Romero S, Sempere A, Gómez-Seguí I, et al. Practice guidelines for the emergency treatment of thrombotic microangiopathy. Guía práctica de tratamiento urgente de la microangiopatía trombótica. Med Clin. 2018;151(3):123.e1–123.e9. doi: 10.1016/j.medcli.2018.01.013
   PubMedGoogle Scholar
• Scully M, Rayment R, Clark A, et al. A British society for haematology guideline: diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies. Br J Haematol. 2023;203(4):546–563. doi: 10.1111/bjh.19026
   PubMed Web of Science ®Google Scholar
• Pascual-Izquierdo C, Piñera Salmerón P, Temboury Ruiz F, et al. Immune thrombotic thrombocytopenic purpura: clinical suspicion and basic management in emergency departments - an expert review and consensus statement from the Spanish societies of hematology and hemotherapy (SEHH) and emergency medicine (SEMES). Púrpura trombocitopénica trombótica inmune: sospecha y manejo básico en los servicios de urgencias. Revisión y consenso de un grupo de expertos de las sociedades científicas SEHH y SEMES. Emergencias. 2023;35(1):44–52.
   PubMed Web of Science ®Google Scholar
• Matsumoto M, Miyakawa Y, Kokame K, et al. Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023. Int J Hematol. 2023;118(5):529–546. doi: 10.1007/s12185-023-03657-0
   PubMed Web of Science ®Google Scholar
• Bull TP, McCulloch R, Nicolson PLR. et al. Diagnostic uncertainty presented barriers to the timely management of acute thrombotic thrombocytopenic purpura in the United Kingdom between 2014 and 2019. J Thromb Haemost. 2022 Jun;20(6):1428–1436.
   PubMed Web of Science ®Google Scholar
• Pascual C, Nieto JM, Fidalgo T, et al. Multicentric evaluation of the new HemosIL Acustar® chemiluminescence ADAMTS13 activity assay. Int J Lab Hematol. 2021;43(3):485–493. doi: 10.1111/ijlh.13414
   PubMed Web of Science ®Google Scholar
• Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol. 2017;4(4):e157–e164. doi: 10.1016/S2352-3026(17)30026-1
   PubMed Web of Science ®Google Scholar
• Coppo P, Schwarzinger M, Buffet M, et al. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience. PloS One. 2010;5(4):e10208. doi: 10.1371/journal.pone.0010208
   PubMed Web of Science ®Google Scholar
• Reeves HM, Maitta RW. Comparison of absolute immature platelet count to the PLASMIC score at presentation in predicting ADAMTS13 deficiency in suspected thrombotic thrombocytopenic purpura. Thromb Res. 2022;215:30–36. doi: 10.1016/j.thromres.2022.05.008
   PubMed Web of Science ®Google Scholar
• Sawler D, Parker A, Britto J, et al. Time from suspected thrombotic thrombocytopenic purpura to initiation of plasma exchange and impact on survival: a 10-year provincial retrospective cohort study. Thromb Res. 2020;193:53–59. doi: 10.1016/j.thromres.2020.05.045
   PubMed Web of Science ®Google Scholar
• Pereira A, Mazzara R, Monteagudo J, et al. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a multivariate analysis of factors predicting the response to plasma exchange. Ann Hematol. 1995;70(6):319–323. doi: 10.1007/BF01696619
   PubMed Web of Science ®Google Scholar
• Kayashima M, Sakai K, Harada K, et al. Strong association between insufficient plasma exchange and fatal outcomes in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura. Int J Hematol. 2021;114(4):415–423. doi: 10.1007/s12185-021-03197-5
   PubMed Web of Science ®Google Scholar
• Balduini CL, Gugliotta L, Luppi M, et al. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010;89(6):591–596. doi: 10.1007/s00277-009-0877-5
   PubMed Web of Science ®Google Scholar
• Clark WF, Rock G, Barth D, et al. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab. Br J Haematol. 2015;170(2):208–217. doi: 10.1111/bjh.13408
   PubMed Web of Science ®Google Scholar
• Cataland SR, Kourlas PJ, Yang S, et al. Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura. Blood Adv. 2017;1(23):2075–2082. doi: 10.1182/bloodadvances.2017009308
   PubMed Web of Science ®Google Scholar
• Benhamou Y, Paintaud G, Azoulay E, et al. Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: results of a phase II, multicenter noncomparative study. Am J Hematol. 2016;91(12):1246–1251. doi: 10.1002/ajh.24559
   PubMed Web of Science ®Google Scholar
• Scully M, McDonald V, Cavenagh J, et al. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood. 2011;118(7):1746–1753. doi: 10.1182/blood-2011-03-341131
   PubMed Web of Science ®Google Scholar
• Zwicker JI, Muia J, Dolatshahi L, et al. Adjuvant low-dose rituximab and plasma exchange for acquired TTP. Blood. 2019;134(13):1106–1109. doi: 10.1182/blood.2019000795
   PubMed Web of Science ®Google Scholar
• Río-Garma J D, Bobillo S, de la Rubia J, et al. Mortality in acquired thrombotic thrombocytopenic purpura in the pre-caplacizumab era. Ann Hematol. 2022;101(1):59–67. doi: 10.1007/s00277-021-04685-8
   PubMed Web of Science ®Google Scholar
• Pascual-Izquierdo C, Del Rio-Garma J, de la Rubia J, et al. Incidence, diagnosis, and outcome of immune-mediated thrombotic thrombocytopenic purpura: a nationwide survey by the Spanish registry of thrombotic thrombocytopenic purpura. J Clin Apheresis. 2021;36(4):563–573. doi: 10.1002/jca.21894
   PubMed Web of Science ®Google Scholar
• Page EE, Kremer Hovinga JA, Terrell DR, et al. Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood Adv. 2017;1(10):590–600. doi: 10.1182/bloodadvances.2017005124
   PubMed Web of Science ®Google Scholar
• Masias C, Wu H, McGookey M, et al. No major differences in outcomes between the initial and relapse episodes in patients with thrombotic thrombocytopenic purpura: the experience from the Ohio State University registry. Am J Hematol. 2018;93(3):E73–5. doi: 10.1002/ajh.25002
   PubMed Web of Science ®Google Scholar
• Italian Group of TTP Investigators, Mancini I, Pontiggia S, Palla R, et al. Clinical and laboratory features of patients with acquired thrombotic Thrombocytopenic Purpura: fourteen years of the Milan TTP registry. Thromb Haemost. 2019 May;119(5):695–704. doi: 10.1055/s-0039-1679907
   PubMed Web of Science ®Google Scholar
• Böhm M, Betz C, Miesbach W, et al. The course of ADAMTS-13 activity and inhibitor titre in the treatment of thrombotic thrombocytopenic purpura with plasma exchange and vincristine. Br J Haematol. 2005;129(5):644–652. doi: 10.1111/j.1365-2141.2005.05512.x
   PubMed Web of Science ®Google Scholar
• Matsumoto M, Bennett CL, Isonishi A, et al. Acquired idiopathic ADAMTS13 activity deficient thrombotic thrombocytopenic purpura in a population from Japan. PloS One. 2012;7(3):e33029. doi: 10.1371/journal.pone.0033029
   PubMed Web of Science ®Google Scholar
• Alwan F, Vendramin C, Vanhoorelbeke K, et al. Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura. Blood. 2017;130(4):466–471. doi: 10.1182/blood-2016-12-758656
   PubMed Web of Science ®Google Scholar
• Westwood JP, Webster H, McGuckin S, et al. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost. 2013;11(3):481–490. doi: 10.1111/jth.12114
   PubMed Web of Science ®Google Scholar
• Jang MJ, Chong SY, Kim IH. et al. Clinical features of severe acquired ADAMTS13 deficiency in thrombotic thrombocytopenic purpura: the Korean TTP registry experience. Int J Hematol. 2011 Feb;93(2):163–169.
   PubMed Web of Science ®Google Scholar
• Benhamou Y, Boelle PY, Baudin B, et al. Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French thrombotic microangiopathies reference center. J Thromb Haemost. 2015;13(2):293–302. doi: 10.1111/jth.12790
   PubMed Web of Science ®Google Scholar
• Benhamou Y, Assié C, Boelle PY, et al. Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA reference center experience. Haematologica. 2012;97(8):1181–1186. doi: 10.3324/haematol.2011.049676
   PubMed Web of Science ®Google Scholar
• Pollissard L, Shah A, Punekar RS, et al. Burden of illness among medicare and non-medicare US populations with acquired thrombotic thrombocytopenic purpura. J Med Econ. 2021;24(1):706–716. doi: 10.1080/13696998.2021.1922262
   PubMed Web of Science ®Google Scholar
• Azoulay E, Bauer PR, Mariotte E, et al. Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura. Intensive care Med. 2019;45(11):1518–1539. doi: 10.1007/s00134-019-05736-5
   PubMed Web of Science ®Google Scholar
• McGuckin S, Westwood JP, Webster H, et al. Characterization of the complications associated with plasma exchange for thrombotic thrombocytopaenic purpura and related thrombotic microangiopathic anaemias: a single institution experience. Vox Sang. 2014;106(2):161–166. doi: 10.1111/vox.12090
   PubMed Web of Science ®Google Scholar
• Som S, Deford CC, Kaiser ML, et al. Decreasing frequency of plasma exchange complications in patients treated for thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 1996 to 2011 (CME). Transfusion. 2012;52(12):2525–2532. doi: 10.1111/j.1537-2995.2012.03646.x
   PubMed Web of Science ®Google Scholar
• Comparon C, Galicier L, Rebibou JM. et al. Preemptive cyclosporin a in immune-mediated thrombotic thrombocytopenic purpura. Eur J Haematol. 2023 Feb;110(2):157–160.
   PubMed Web of Science ®Google Scholar
• Benhamou Y, Sauvètre G, Grangé S, et al. Venous thrombo-embolism during immune-mediated thrombotic thrombocytopenic purpura is prevalent in patients with a prolonged treatment with therapeutic plasma exchange. Rev Med Interne. 2020;41(12):809–813. doi: 10.1016/j.revmed.2020.06.014
   PubMed Web of Science ®Google Scholar
• Riva S, Mancini I, Maino A, et al. Long-term neuropsychological sequelae, emotional wellbeing and quality of life in patients with acquired thrombotic thrombocytopenic purpura. Haematologica. 2020;105(7):1957–1962. doi: 10.3324/haematol.2019.226423
   PubMed Web of Science ®Google Scholar
• Alwan F, Mahdi D, Tayabali S, et al. Cerebral MRI findings predict the risk of cognitive impairment in thrombotic thrombocytopenic purpura. Br J Haematol. 2020;191(5):868–874. doi: 10.1111/bjh.17126
   PubMed Web of Science ®Google Scholar
• Chaturvedi S, Oluwole O, Cataland S, et al. Post-traumatic stress disorder and depression in survivors of thrombotic thrombocytopenic purpura. Thromb Res. 2017;151:51–56. doi: 10.1016/j.thromres.2017.01.003
   PubMed Web of Science ®Google Scholar
• George JN. TTP: long-term outcomes following recovery. Hematol Am Soc Hematol Educ Program. 2018;2018(1):548–552. doi: 10.1182/asheducation-2018.1.548
   PubMedGoogle Scholar
• Brodsky MA, Sukumar S, Selvakumar S, et al. Major adverse cardiovascular events in survivors of immune-mediated thrombotic thrombocytopenic purpura. Am J Hematol. 2021;96(12):1587–1594. doi: 10.1002/ajh.26341
   PubMed Web of Science ®Google Scholar
• Scully M, Dutt T, Lester W, et al. Unmet needs in the management of immune-mediated thrombotic thrombocytopenic purpura and the potential role of caplacizumab in the UK-A modified-delphi study. EJHaem. 2022 Apr 28;3(3):619–627. doi: 10.1002/jha2.435
   PubMedGoogle Scholar
• Scully M, de la Rubia J, Pavenski K, et al. Long-term follow-up of patients treated with caplacizumab and safety and efficacy of repeat caplacizumab use: post-HERCULES study. J Thromb Haemost. 2022;20(12):2810–2822. doi: 10.1111/jth.15892
   PubMed Web of Science ®Google Scholar
• Miyakawa Y, Imada K, Ichikawa S, et al. The efficacy and safety of caplacizumab in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura: an open-label phase 2/3 study. Int J Hematol. 2023;117(3):366–377. doi: 10.1007/s12185-022-03495-6
   PubMed Web of Science ®Google Scholar
• Tse B, Buchholz M, Pavenski K. Management of immune thrombotic thrombocytopenic purpura with caplacizumab: a Canadian, single-centre, real-world experience. Platelets. 2023;34(1):2157807. doi: 10.1080/09537104.2022.2157807
   PubMed Web of Science ®Google Scholar
• Chaturvedi S. Counting the cost of caplacizumab. Blood. 2021;137(7):871–872. doi: 10.1182/blood.2020009250
   PubMed Web of Science ®Google Scholar
• He J, Qi J, Han H, et al. Efficacy and safety of caplacizumab in the treatment of thrombotic thrombocytopenic purpura: a systematic review and meta-analysis. Expert Rev Hematol. 2023;16(5):377–385. doi: 10.1080/17474086.2023.2202850
   PubMed Web of Science ®Google Scholar
• Chen B, Li X, Xiao D, et al. Comparison of the efficacy and safety of caplacizumab versus placebo in thrombotic thrombocytopenic purpura: a meta-analysis and systematic review based on randomized controlled trials. Ann Transl Med. 2022;10(12):657. doi: 10.21037/atm-22-2847
   PubMed Web of Science ®Google Scholar
• Cuker A, Cataland SR, Coppo P, et al. Redefining outcomes in immune TTP: an international working group consensus report. Blood. 2021;137(14):1855–1861. doi: 10.1182/blood.2020009150
   PubMed Web of Science ®Google Scholar
• Gómez-Seguí I, Francés Aracil E, Mingot-Castellano ME, et al. Immune thrombotic thrombocytopenic purpura in older patients: results from the Spanish TTP registry (REPTT). Br J Haematol. 2023;203(5):860–871. doi: 10.1111/bjh.19109
   PubMed Web of Science ®Google Scholar
• Schofield J, Shaw RJ, Lester W, et al. Intracranial hemorrhage in immune thrombotic thrombocytopenic purpura treated with caplacizumab. J Thromb Haemost. 2021;19(8):1922–1925. doi: 10.1111/jth.15363
   PubMed Web of Science ®Google Scholar
• Ditzel K, Mons DJ, Fijnheer R. Fatal cerebral hemorrhage in a patient with thrombotic thrombocytopenic purpura with a normal platelet count during treatment with caplacizumab. Platelets. 2022;33(3):484–485. doi: 10.1080/09537104.2021.1922883
   PubMed Web of Science ®Google Scholar
• Connell NT, Flood VH, Brignardello-Petersen R, et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv. 2021;5(1):301–325. doi: 10.1182/bloodadvances.2020003264
   PubMed Web of Science ®Google Scholar
• Hughes M, Prescott C, Elliott N. Et aI. NICE guidance on caplacizumab for treating acute acquired thrombotic thrombocytopenia purpura. Lancet Haematol. 2021;8(1):e14–e15. doi: 10.1016/S2352-3026(20)30406-3
   PubMed Web of Science ®Google Scholar
• Mazepa MA, Masias C, Chaturvedi S. How targeted therapy disrupts the treatment paradigm for acquired TTP: the risks, benefits, and unknowns. Blood. 2019;134(5):415–420. doi: 10.1182/blood.2019000954
   PubMed Web of Science ®Google Scholar
• Völker LA, Kaufeld J, Miesbach W, et al. ADAMTS13 and VWF activities guide individualized caplacizumab treatment in patients with aTTP. Blood Adv. 2020;4(13):3093–3101. doi: 10.1182/bloodadvances.2020001987
   PubMed Web of Science ®Google Scholar
• Kühne L, Kaufeld J, Völker LA, et al. Alternate-day dosing of caplacizumab for immune-mediated thrombotic thrombocytopenic purpura. J Thromb Haemost. 2022;20(4):951–960. doi: 10.1111/jth.15637
   PubMed Web of Science ®Google Scholar
• Abou-Ismail MY, Zhang C, Presson A, et al. Investigators USTMC. mortality in acute immune-mediated thrombotic thrombocytopenic purpura (iTTP) is unpredictable: poor statistical performance of mortality prediction models. Blood. 2021;138(Supplement 1):771. doi: 10.1182/blood-2021-146282
   Google Scholar
• Scully M, Yarranton H, Liesner R, et al. Regional UK TTP registry: correlation with laboratory ADAMTS 13 analysis and clinical features. Br J Haematol. 2008;142(5):819–826. doi: 10.1111/j.1365-2141.2008.07276.x
   PubMed Web of Science ®Google Scholar
• Lotta LA, Mariani M, Consonni D, et al. Different clinical severity of first episodes and recurrences of thrombotic thrombocytopenic purpura. Br J Haematol. 2010;151(5):488–494. doi: 10.1111/j.1365-2141.2010.08385.x
   PubMed Web of Science ®Google Scholar
• Joseph A, Joly BS, Picod A, et al. The specificities of thrombotic thrombocytopenic purpura at extreme ages: a narrative review. J Clin Med. 2023;12(9):3068. doi: 10.3390/jcm12093068
   PubMed Web of Science ®Google Scholar
• Bergstrand M, Hansson E, Delaey B, et al. Caplacizumab model-based dosing recommendations in pediatric patients with acquired thrombotic thrombocytopenic purpura. J Clin Pharmacol. 2022;62(3):409–421. doi: 10.1002/jcph.1991
   PubMed Web of Science ®Google Scholar
• Kaczmarek V, Holle J, Astudillo R, et al. Caplacizumab for relapsing thrombotic thrombocytopenic purpura. Pediatr Nephrol. 2019;34(9):1625–1628. doi: 10.1007/s00467-019-04281-z
   PubMed Web of Science ®Google Scholar
• Boudali J, Hallak B, Haeck M, et al. Immune-mediated thrombotic thrombocytopenic purpura in childhood treated by caplacizumab, about 3 cases. J Nephrol. 2022;35(2):653–656. doi: 10.1007/s40620-021-00992-5
   PubMed Web of Science ®Google Scholar
• Tripiciano C, Zangari P, Montanari M, et al. Case report: two cases of pediatric thrombotic thrombocytopenic purpura treated with combined therapy. Front Pediatr. 2021;9:743206. doi: 10.3389/fped.2021.743206
   PubMed Web of Science ®Google Scholar
• Veltroni M, Pegoraro F, Scappini B. et al. Off-label caplacizumab as add-on therapy in a 9-year-old boy with refractory aTTP. Ann Hematol. 2022 Jun;101(6):1369–1371.
   PubMed Web of Science ®Google Scholar
• Tran TB, Boyce J, Mitchell H, et al. Real-world experience of caplacizumab for adolescents in the first-line setting: case reports. J Pediatr Hematol Oncol. 2023;45(8):e1031–e1034. doi: 10.1097/MPH.0000000000002716
   PubMed Web of Science ®Google Scholar
• Maitta RW, Reeves HM, Downes KA, et al. Immature platelet dynamics in management of protracted response to therapy of a young pediatric patient with immune-mediated thrombotic thrombocytopenic purpura. Thromb Res. 2023;228:145–147. doi: 10.1016/j.thromres.2023.06.002
   PubMed Web of Science ®Google Scholar
• Scully M, Thomas M, Underwood M, et al. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood. 2014;124(2):211–219. doi: 10.1182/blood-2014-02-553131
   PubMed Web of Science ®Google Scholar
• Fakhouri F, Scully M, Provôt F, et al. Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group. Blood. 2020;136(19):2103–2117. doi: 10.1182/blood.2020005221
   PubMed Web of Science ®Google Scholar
• Kühne L, Völker LA, Hagmann H, et al. First use of the anti-VWF nanobody caplacizumab to treat iTTP in pregnancy. Br J Haematol. 2022;196(3):e30–e33. doi: 10.1111/bjh.17833
   PubMed Web of Science ®Google Scholar
• Odetola O, Martin KA, Dreyer M, et al. A safe and effective use of caplacizumab in pregnancy-related acquired thrombotic thrombocytopenic purpura. Br J Haematol. 2023;202(4):879–882. doi: 10.1111/bjh.18888
   PubMed Web of Science ®Google Scholar
• Bruzzese A, Vigna E, Martino EA, et al. Safety and efficacy of caplacizumab in a case of thrombotic thrombocytopenic purpura in the postpartum period. Blood Coagul Fibrinolysis. 2023;34(3):215–217. doi: 10.1097/MBC.0000000000001186
   PubMed Web of Science ®Google Scholar
• Völker LA, Brinkkoetter PT, Knöbl PN, et al. Treatment of acquired thrombotic thrombocytopenic purpura without plasma exchange in selected patients under caplacizumab. J Thromb Haemost. 2020;18(11):3061–3066. doi: 10.1111/jth.15045
   PubMed Web of Science ®Google Scholar
• Wang J, Cheng F, Niu Y, et al. Therapeutic plasma exchange-free treatment for first-episode TTP: a systematic review. Transfus Apher Sci. 2023;62(3):103661. doi: 10.1016/j.transci.2023.103661
   PubMed Web of Science ®Google Scholar
• Sukumar S, Brodsky M, Hussain S, et al. Cardiovascular disease is a leading cause of mortality among TTP survivors in clinical remission. Blood Adv. 2022;6(4):1264–1270. doi: 10.1182/bloodadvances.2020004169
   PubMed Web of Science ®Google Scholar
• Upreti H, Kasmani J, Dane K, et al. Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors. Blood. 2019;134(13):1037–1045. doi: 10.1182/blood.2019001056
   PubMed Web of Science ®Google Scholar
• Sonneveld MA, Franco OH, Ikram MA, et al. Von Willebrand factor, ADAMTS13, and the risk of mortality: the Rotterdam study. Arterioscler Thromb Vasc Biol. 2016;36(12):2446–2451. doi: 10.1161/ATVBAHA.116.308225
   PubMed Web of Science ®Google Scholar
• Bongers TN, de Bruijne EL, Dippel DW, et al. Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients. Atherosclerosis. 2009;207(1):250–254. doi: 10.1016/j.atherosclerosis.2009.04.013
   PubMed Web of Science ®Google Scholar
• Sonneveld MA, de Maat MP, Portegies ML, et al. Low ADAMTS13 activity is associated with an increased risk of ischemic stroke. Blood. 2015;126(25):2739–2746. doi: 10.1182/blood-2015-05-643338
   PubMed Web of Science ®Google Scholar
• Yarranton H, Cohen H, Pavord SR, et al. Venous thromboembolism associated with the management of acute thrombotic thrombocytopenic purpura. Br J Haematol. 2003;121(5):778–785. doi: 10.1046/j.1365-2141.2003.04360.x
   PubMed Web of Science ®Google Scholar
• Camous L, Veyradier A, Darmon M, et al. Macrovascular thrombosis in critically ill patients with thrombotic micro-angiopathies. Intern Emerg Med. 2014;9(3):267–272. doi: 10.1007/s11739-012-0851-4
   PubMed Web of Science ®Google Scholar
• Elverdi T, Özer Çerme MD, Aydın T, et al. Do patients with immune-mediated thrombotic thrombocytopenic purpura receiving caplacizumab need antithrombotic therapy? Expert Rev Clin Pharmacol. 2021;14(10):1183–1188. doi: 10.1080/17512433.2021.1944102
   PubMed Web of Science ®Google Scholar
• Picod A, Veyradier A, Coppo P. Should all patients with immune-mediated thrombotic thrombocytopenic purpura receive caplacizumab? J Thromb Haemost. 2021;19(1):58–67. doi: 10.1111/jth.15194
   PubMed Web of Science ®Google Scholar
• Schutgens REG, Jimenez-Yuste V, Escobar M, et al. Antithrombotic treatment in patients with hemophilia: an EHA-ISTH-EAHAD-ESO clinical practice guidance. Hemasphere. 2023;7(6):e900. doi: 10.1097/HS9.0000000000000900
   PubMed Web of Science ®Google Scholar
• Shaw RJ, Dutt T. Mind and matter: the neurological complications of thrombotic thrombocytopenic purpura. Br J Haematol. 2022 Jun;197(5):529–538. doi: 10.1111/bjh.18127
   PubMed Web of Science ®Google Scholar
• Saultz JN, Wu HM, Cataland S. Headache prevalence following recovery from TTP and aHUS. Ann Hematol. 2015;94(9):1473–1476. doi: 10.1007/s00277-015-2411-2
   PubMed Web of Science ®Google Scholar
• Kennedy AS, Lewis QF, Scott JG, et al. Cognitive deficits after recovery from thrombotic thrombocytopenic purpura. Transfusion. 2009;49(6):1092–1101. doi: 10.1111/j.1537-2995.2009.02101.x
   PubMed Web of Science ®Google Scholar
• Cataland SR, Scully MA, Paskavitz J, et al. Evidence of persistent neurologic injury following thrombotic thrombocytopenic purpura. Am J Hematol. 2011;86(1):87–89. doi: 10.1002/ajh.21881
   PubMed Web of Science ®Google Scholar
• Prasannan N, Thomas M, Stubbs M, et al. Delayed normalization of ADAMTS13 activity in acute thrombotic thrombocytopenic purpura in the caplacizumab era. Blood. 2023;141(18):2206–2213. doi: 10.1182/blood.2022018847
   PubMed Web of Science ®Google Scholar
• Mingot-Castellano ME, García-Candel F, Martínez-Nieto J, et al. ADAMTS13 recovery in acute thrombotic thrombocytopenic pupura after caplacizumab therapy. The Spanish registry. Blood. 2023;142(Supp 1):5394. doi: 10.1182/blood-2023-182876
   Google Scholar
• Kucukyurt S, Eskazan AE. Assessment and monitoring of patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP): strategies to improve outcomes. J Blood Med. 2020;11:319–326. doi: 10.2147/JBM.S205630
   PubMed Web of Science ®Google Scholar
• Underwood MI, Alwan F, Thomas MR, et al. Autoantibodies enhance ADAMTS-13 clearance in patients with immune thrombotic thrombocytopenic purpura. J Thromb Haemost. 2023;21(6):1544–1552. doi: 10.1016/j.jtha.2023.02.011
   PubMed Web of Science ®Google Scholar
• Ellier E, Widemann A, Cauchois R, et al. Immune-mediated thrombotic thrombocytopenic purpura plasma induces calcium and IgG-dependent endothelial activation: correlations with disease severity. Haematologica. 2023;108(4):1127–1140. doi: 10.3324/haematol.2022.280651
   PubMed Web of Science ®Google Scholar
• Di Minno G, Ravasio R. Cost-effectiveness analysis of caplacizumab in the new standard of care for immune thrombotic thrombocytopenic purpura in Italy. GRHTA. 2021;8:43–52.
   Google Scholar
• Coppo P, Bubenheim M, Benhamou Y, et al. Caplacizumab frontline added to therapeutic plasma exchange and immunosuppression prevents unfavorable outcomes in immune-mediated TTP: an international real-world study of the TTP-IWG (the Capla 500 Project). Blood. 2023;142(Supplement 1):2636. doi: 10.1182/blood-2023-179316
   Google Scholar