Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods

Abstract

Drug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinical criteria, 87 (34%) were identified with evidence that the drug caused thrombocytopenia. (2) Serum samples from patients with suspected DITP were tested for 202 drugs; drug-dependent, platelet-reactive antibodies were identified for 67 drugs (33%). (3) The Food and Drug Administration's Adverse Event Reporting System database was searched for drugs associated with thrombocytopenia by use of data mining algorithms; 1444 drugs had at least 1 report associated with thrombocytopenia, and 573 (40%) drugs demonstrated a statistically distinctive reporting association with thrombocytopenia. Among 1468 drugs suspected of causing thrombocytopenia, 102 were evaluated by all 3 methods, and 23 of these 102 drugs had evidence for an association with thrombocytopenia by all 3 methods. Multiple methods, each with a distinct perspective, can contribute to the identification of drugs that can cause thrombocytopenia.

Figure 1

Results of analysis by the 3 distinct methods. (A) Results of analysis by published case reports and the relation of the results to analysis by the other 2 methods. Not all of the 87 drugs with evidence in case reports were also analyzed by the other 2 methods. (B) Results of analysis by laboratory detection of drug-dependent, platelet-reactive antibodies and the relation of the results to analysis by the other 2 methods. Not all of the 67 drugs with evidence by documentation of drug-dependent antibodies were also analyzed by the other 2 methods. (C) Results of analysis by data mining of the AERS database and the relation of the results to analysis by the other 2 methods. Not all of the 573 drugs with evidence in the AERS database were also analyzed by the other 2 methods.