Drug-induced thrombocytopenia: A systematic review of published case reports

Purpose: To determine the strength of clinical evidence for individual drug s as a cause of thrombocytopenia. Data Sources: All English-language reports on drug-induced thrombocytopenia . Study Selection: Articles describing thrombocytopenia caused by heparin wer e excluded from review. Of the 581 articles reviewed, 20 were excluded beca use they contained no patient case reports. The remaining 561 articles repo rted on 774 patients. Data Extraction: Two of the authors used a priori criteria to independently review each patient case report. Two hundred fifty-nine patient case repor ts were excluded from further review because of lack of evaluable data, pla telet count of 100 000 cells/mu L or more, use of cytotoxic or nontherapeut ic agents, occurrence of drug-induced systemic disease, or occurrence of di sease in children. For the remaining 515 patient case reports, a level of e vidence for the drug as the cause of thrombocytopenia was assigned. Data on bleeding complications and clinical course were recorded. Data Synthesis: The evidence supported a definite or probable causal role f or the drug in 247 patient case reports (48%). Among the 98 drugs described in these reports, quinidine was mentioned in 38 case reports, gold in 11, and trimethoprim-sulfamethoxazole in 10. Of the 247 patients described in t he case reports, 23 (9%) had major bleeding and 2 (0.8%) died of bleeding. Conclusions: Many reports of drug-induced thrombocytopenia do not provide e vidence supporting a definite or probable causal relation between the disea se and the drug. Future patient case reports should incorporate standard cr iteria to clearly establish the etiologic role of the drug.