Abstract
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.
Keywords
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Article info
Publication history
Published online: February 28, 2023
Publication stage
In Press Journal Pre-ProofIdentification
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© 2023 Elsevier Ltd. All rights reserved.
