Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life‐threatening thrombotic microangiopathy (TMA), characterized by disseminated thrombus formation in the microvasculature, causing severe organ failure. Immune‐mediated TTP is occasionally described after vaccination, especially against viral agents. We report a case of a 38‐year old woman with a de novo iTTP after exposure to the mRNA‐based anti‐COVID‐19 vaccine produced by Pfizer‐BioNTech. She presented with increased bruising and petechiae, starting 2 weeks after receiving the first dose of the anti‐COVID‐19 vaccine. Laboratory data revealed a severe ADAMTS13‐deficiency in combination with a very high autoantibody titer against ADAMTS13. She was successfully treated with plasma exchange, corticosteroids, rituximab and Caplacizumab. To our knowledge, this is the first case report of iTTP post mRNA‐based COVID‐19‐vaccination in a previously TTP‐naïve patient.
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is caused by an autoantibody-mediated deficiency of ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats member 13). In healthy individuals, ADAMTS13 has a folded conformation where the central spacer domain interacts with the C-terminal CUB domains. We recently showed that ADAMTS13 adopts an open conformation in iTTP and that patient immunoglobulin G's (IgGs) can open ADAMTS13. Anti-ADAMTS13 autoantibodies in iTTP patients are directed against the different ADAMTS13 domains but almost all patients have autoantibodies binding to the cysteine/spacer (CS) domains. In this study, we investigated whether the autoantibodies against the CS and CUB domains can disrupt the S-CUB interaction of folded ADAMTS13 thereby opening ADAMTS13. Therefore, we purified anti-CS and anti-CUB autoantibodies from 13 acute iTTP patients by affinity chromatography. The successfully purified anti-CS (10/13 patients) and anti-CUB (4/13 patients) autoantibody fractions were further tested in our ADAMTS13 conformation ELISA to study whether they could open ADAMTS13. Interestingly, all purified anti-CS fractions (10/10 patients) were able to open ADAMTS13. On the other hand, only half of the purified anti-CUB fractions (2/4 patients) opened ADAMTS13. Our finding highlights that anti-CS autoantibodies that open ADAMTS13 are a common feature of the autoimmune response in iTTP.
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