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Drug-Induced Thrombocytopenia: A Systematic Review of Published Case Reports

James N. George, MD; Gary E. Raskob, MSc; Shehla Rizvi Shah, MD; Mujahid A. Rizvi, MD; Stephen A. Hamilton, MD; Scott Osborne, BA; and Thomas Vondracek, PharmD
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From University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Note: A complete list of drugs implicated in patient case reports can also be found in the electronic version of this paper at http://www.acponline.org. Requests for Reprints: James N. George, MD, Hematology-Oncology Section, Department of Medicine, University of Oklahoma Health Sciences Center, Box 26901, Oklahoma City, OK 73190. Current Author Addresses: Dr. George: Hematology-Oncology Section, Department of Medicine, University of Oklahoma Health Sciences Center, Box 26901, Oklahoma City, OK 73190. Mr. Raskob, Drs. Shah and Rizvi, and Mr. Osborne: Department of Medicine, University of Oklahoma Health Sciences Center, Box 26901, Oklahoma City, OK 73190. Dr. Hamilton: Cancer Treatment Center, 230 North Midwest Boulevard, Suite 200, Midwest City, OK 73110. Dr. Vondracek: College of Pharmacy, 1110 North Stonewall, Oklahoma City, OK 73104.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1998;129(11_Part_1):886-890. doi:10.7326/0003-4819-129-11_Part_1-199812010-00009
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Purpose: To determine the strength of clinical evidence for individual drugs as a cause of thrombocytopenia.

Data Sources: All English-language reports on drug-induced thrombocytopenia.

Study Selection: Articles describing thrombocytopenia caused by heparin were excluded from review. Of the 581 articles reviewed, 20 were excluded because they contained no patient case reports. The remaining 561 articles reported 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 reports were excluded from further review because of lack of evaluable data, platelet count of 100 000 cells/µL or more, use of cytotoxic or nontherapeutic agents, occurrence of drug-induced systemic disease, or occurrence of disease in children. For the remaining 515 patient case reports, a level of evidence 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 for 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 the case reports, 23 (9%) had major bleeding and 2 (0.8%) died of bleeding.

Conclusions: Many reports of drug-induced thrombocytopenia do not provide evidence supporting a definite or probable causal relation between the disease and the drug. Future patient case reports should incorporate standard criteria to clearly establish the etiologic role of the drug.





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