Drug‐induced thrombotic thrombocytopenic purpura: A systematic review and review of European and North American pharmacovigilance data

Abstract

Summary Many medications have been reported to be associated with thrombotic thrombocytopenic purpura (TTP) through pharmacovigilance data and published case reports. Whilst there are existing data available regarding drug‐induced thrombotic microangiopathy, there is no available synthesis of evidence to assess drug‐induced TTP (DI‐TTP). Despite this lack of evidence, patients with TTP are often advised against using many medications due to the theoretical risk of DI‐TTP. This systematic review evaluated the evidence for an association of medications reported as potential triggers for TTP. Of 5098 records available 261 articles were assessed further for eligibility. Fifty‐seven reports, totalling 90 patients, were included in the final analysis. There were no cases where the level of association was rated as definite or probable, demonstrating a lack of evidence of any drug causing DI‐TTP. This paucity of evidence was also demonstrated in the pharmacovigilance data, where 613 drugs were reported as potential causes of TTP without assessment of the strength of association. This systematic review demonstrates the need for standardised reporting of potential drugs causing TTP. Many reports omit basic information and, therefore, hinder the chance of finding a causative link if one exists.

Alemtuzumab‐induced immune‐mediated thrombotic thrombocytopenic purpura: A newly described drug‐related autoimmune disease

“…11,13 Some observations of drug-induced iTTP involving inhibition of ADAMTS13 and anti-ADAMTS13 antibody have, however, been reported (mainly with anti-platelet ticlopidine withdrawn for the market, rarely with other drugs as prasugrel, clopidogrel, leflunomide, pembrolizumab). 2 The first case of TTP in alemtuzumab-treated patients, requiring ICU and plasmapheresis, was identified in a Finnish nationwide cohort of 121 RR-MS and secondaryprogressive MS patients. 14 No data on clinical manifestations, ADAMTS13 status, time between the administration and the occurrence of the TTP or evolution were available.…”

“…Some observations of drug‐induced iTTP involving inhibition of ADAMTS13 and anti‐ADAMTS13 antibody have, however, been reported (mainly with anti‐platelet ticlopidine withdrawn for the market, rarely with other drugs as prasugrel, clopidogrel, leflunomide, pembrolizumab) 2 …”

“…Pathophysiologically, the disease results from a severe antibody‐mediated deficiency in ADAMTS13 (activity <10%), the specific von Willebrand factor‐cleaving protease 1 . Several causal factors have previously been identified, such as infections (especially HIV), pre‐existing systemic autoimmune diseases (especially the systemic lupus erythematosus), pregnancy and drugs including anti‐platelet agents, checkpoint inhibitors and lenalidomide 1,2 . We report here the second case of TTP allegedly attributed to alemtuzumab, a humanized anti‐CD52 monoclonal antibody.…”

“…1 Several causal factors have previously been identified, such as infections (especially HIV), pre-existing systemic autoimmune diseases (especially the systemic lupus erythematosus), pregnancy and drugs including anti-platelet agents, checkpoint inhibitors and lenalidomide. 1,2 We report here Summary Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and lifethreatening disease that may result from drug exposure. We report a case of iTTP occurring in a 39-year-old patient, 45 months following introduction of the anti-CD52 lymphoid cell depleting monoclonal antibody alemtuzumab, to treat a relapsingremitting multiple sclerosis.…”

Drug‐induced thrombotic microangiopathy and thrombotic thrombocytopenic purpura: A systematic review, 2018–2023

“…3 Using our criteria to evaluate reports of DITMA, 1 which they adapted for evaluating reports of drug-induced TTP (DI-TTP), Scholfield et al recently reviewed 90 reports (describing 97 drugs) that described DI-TTP. 4 They concluded that none of the 97 drugs (including the two drugs and two ICIs that we identified as having probable evidence for causing DI-TTP) had definite or probable evidence for causing TTP. We address this discrepency in this report.…”