Review Article|Articles in Press, 103682

Thrombotic thrombocytopenic purpura in caplacizumab era – An individualized approach

  • Ravi Sarode
    Correspondence address: Pathology and Internal Medicine (Hematology/Oncology), UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, USA.
    Departments of Pathology and Internal Medicine (Hematology/Oncology), UT Southwestern Medical Center, Dallas, TX, USA
    Search for articles by this author
Published:February 28, 2023DOI:


      Thrombotic thrombocytopenic purpura (TTP) is a rare disease characterized by a severe deficiency (< 10 % activity) of ADAMTS13 enzyme due to an autoantibody (aTTP) or genetic defect leading to congenital TTP (cTTP). The management of aTTP has evolved over the last 30 years, beginning with plasma exchange (PLEX) being the standard of care, leading to gradual aggressive immunosuppression therapies to manage exacerbations and relapses. Although PLEX had reversed the mortality from > 90 % to < 10–20 %, early deaths do occur in severe aTTP, especially when there is a delay in diagnosis and/or PLEX initiation. There is growing evidence that aTTP is often associated with the long-term neuropsychiatric sequela, probably associated with brain damage caused by microthromboses. Recently, a disease-modifying agent, caplacizumab, a potent nanobody that inhibits the interaction between the A1 domain of von Willebrand factor with GPIb on platelets, was approved by various agencies for the treatment of aTTP. Two clinical trials showed its efficacy in rapidly correcting platelet counts and preventing exacerbations because caplacizumab was continued for 30 days post-PLEX, irrespective of ADAMTS13 recovery. However, caplacizumab was associated with higher and unusual bleeding side effects compared to the placebo due to a severe acquired von Willebrand syndrome that persisted for the duration of therapy. Because of its longer half-life coupled with early aggressive rituximab therapy, it is prudent to use caplacizumab judiciously to avoid serious bleeds and to reduce costs. This manuscript provides a rational approach for using caplacizumab, an important disease-modifying agent.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Transfusion and Apheresis Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Zheng X.L.
        • Vesely S.K.
        • Catalan S.R.
        • et al.
        ISTH guidelines for treating thrombotic thrombocytopenic purpura.
        J Thromb Haemost. 2020; 18: 2496-2502
        • Shaw R.J.
        • Dutt T.
        Mind and matter: the neurological complications of thrombotic thrombocytopenic purpura.
        Br J Haematol. 2022; 197: 529-538
        • Westwood J.-P.
        • Webster H.
        • McGuckin S.
        • McDonald V.
        • Machin S.J.
        • Scully M.
        Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse.
        J Thromb Haemost. 2013; 11: 481-490
        • Callewaert F.
        • Roodt J.
        • Ulrichts H.
        • et al.
        Evaluation of efficacy and safety of the anti-VWF nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura.
        Blood. 2012; 120: 3603-3610
        • Peyvandi F.
        • Scully M.
        • Kremer Hovinga J.A.
        • et al.
        Caplacizumab for acquired thrombotic thrombocytopenic purpura.
        N Engl J Med. 2016; 374: 511-522
        • Scully M.
        • Cataland S.R.
        • Peyvandi F.
        • et al.
        aplacizumab treatment for acquired thrombotic thrombocytopenic purpura.
        N Engl J Med. 2019; 380: 335-346
        • Goshua G.
        • Bendapudi P.K.
        Evidence-based minireview: should caplacizumab be used routinely in unselected patients with immune thrombotic thrombocytopenic purpura?.
        Hematol Am Soc Hematol Educ Program. 2022; 2022: 491-494
        • Kaufeld J.
        • Brinkkoetter P.T.
        • Schreiber A.
        • et al.
        Caplacizumab: frequent local skin reactions.
        Ann Hematol. 2021; 100: 3051-3052
        • Ditzel K.
        • Mons D.J.
        • Fijnheer R.
        Fatal cerebral hemorrhage in a patient with thrombotic thrombocytopenic purpura with a normal platelet count during treatment with caplacizumab.
        Platelets. 2022; 33: 484-485
        • Schofield J.
        • Shaw R.J.
        • Lester W.
        • Thomas W.
        • Toh C.H.
        • Dutt T.
        Intracranial hemorrhage in immune thrombotic thrombocytopenic purpura treated with caplacizumab.
        J Thromb Haemost. 2021; 19: 1922-1925
        • Kühne L.
        • Kaufeld J.
        • Völker L.A.
        • et al.
        Alternate-day dosing of caplacizumab for immune-mediated thrombotic thrombocytopenic purpura.
        Thromb Haemost. 2022; 20: 951-960
        • Fuchs T.A.
        • Kremer Hovinga J.A.
        • Schatzberg D.
        • Wagner D.D.
        • Lämmle B.
        Circulating DNA, and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies.
        Blood. 2012; 120: 1157-1164
        • Masias C.
        • Cataland S.R.
        The role of ADAMTS13 testing in the diagnosis and management of thrombotic microangiopathies and thrombosis.
        Blood. 2018; 132: 903-910
        • Chen M.
        • Shortt J.
        Plasma cell directed therapy for immune thrombotic thrombocytopenic purpura (iTTP).
        Transfus Med Rev. 2022; 36: 204-214