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.
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Published online: February 28, 2023
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