Drug-induced thrombotic microangiopathy: Experience of the Oklahoma Registry and the BloodCenter of Wisconsin

Abstract

Many drugs have been reported to cause thrombotic microangiopathy (TMA), often described as thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS). We recently established criteria to evaluate the evidence for a causal association of a drug with TMA and then we systematically reviewed all published reports of drug-induced TMA (DITMA) to determine the level of evidence supporting a causal association of the suspected drug with TMA. On the basis of this experience, we used these evaluation criteria to assess the Oklahoma TTP-HUS Registry patients who had been previously categorized as drug-induced, 1989-2014. We also reviewed the experience of the BloodCenter of Wisconsin with testing for drug-dependent antibodies reactive with platelets and neutrophils in patients with suspected immune-mediated DITMA, 1988-2014. Among 58 patients in the Oklahoma Registry previously categorized as drug-induced (15 suspected drugs), 21 patients (three drugs: gemcitabine, pentostatin, quinine) had evidence supporting a definite association with TMA; 19 (90%) of the 21 patients had quinine-induced TMA. The BloodCenter of Wisconsin tested 40 patients with suspected DITMA (eight drugs); drug-dependent antibodies, supporting a definite association with TMA, were identified in 30 patients (three drugs: oxaliplatin, quinine, vancomycin); 28 (93%) of the 30 patients had quinine-induced TMA. Combining the data from these two sources, 51 patients (five drugs) have been identified with evidence supporting a definite association with TMA. DITMA was attributed to quinine in 47 (92%) of these 51 patients.