A systematic evaluation of laboratory testing for drug‐induced immune thrombocytopenia

BACKGROUND: Drug-induced immune thrombocytopenia (DITP) can be confirmed by the demonstration of drug-dependent platelet antibodies in vitro; however, laboratory testing is not readily accessible and test methods are not standardized. OBJECTIVE: To identify drugs with the strongest evidence for causing DITP based on clinical and laboratory criteria. PATIENTS/METHODS: We developed a grading system to evaluate the quality of DITP laboratory testing. The 'DITP criteria' were: (i) Drug (or metabolite) was required for the reaction in vitro; (ii) Immunoglobulin binding was demonstrated; (iii) Two or more laboratories obtained positive results; and (iv) Platelets were the target of immunoglobulin binding. Laboratory diagnosis of DITP was considered definite when all criteria were met and probable when positive results were reported by only one laboratory. Two authors applied the DITP criteria to published reports of each drug identified by systematic review. Discrepancies were independently adjudicated. RESULTS: Of 153 drugs that were clinically implicated in thrombocytopenic reactions, 72 (47%) were associated with positive laboratory testing. Of those, 16 drugs met criteria for a definite laboratory diagnosis of DITP and thus had the highest probability of causing DITP. Definite drugs were: quinine, quinidine, trimethoprim/sulfamethoxazole, vancomycin, penicillin, rifampin, carbamazepine, ceftriaxone, ibuprofen, mirtazapine, oxaliplatin and suramin; the glycoprotein IIbIIIa inhibitors abciximab, tirofiban and eptifibatide; and heparin. CONCLUSIONS: We identified drugs with the strongest evidence for an association with immune thrombocytopenia. This list may be helpful for ranking potential causes of thrombocytopenia in a given patient.