title: 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.
authors: Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors: Jessica A
authors: JA
authors: Reese
authors: Daniel W
authors: DW
authors: Bougie
authors: Brian R
authors: BR
authors: Curtis
authors: Deirdra R
authors: DR
authors: Terrell
authors: Sara K
authors: SK
authors: Vesely
authors: Richard H
authors: RH
authors: Aster
authors: James N
authors: JN
authors: George
mesh_terms: D000554:Ambulatory Care Facilities / Q000706:statistics & numerical data; D000906:Antibodies / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D009825:Oklahoma; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D015649:Pentostatin / Q000008:administration & dosage / Q000009:adverse effects; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D011803:Quinine / Q000008:administration & dosage / Q000009:adverse effects*; D012042:Registries; D057049:Thrombotic Microangiopathies / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects; D014922:Wisconsin; D000093542:Gemcitabine
chemical_list: D000906:Antibodies; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D015649:Pentostatin; D014640:Vancomycin; D011803:Quinine; D000093542:Gemcitabine
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