Piperacillin–tazobactam-associated thrombocytopenia with negative antiplatelet antibody testing: a case report and literature review

Background: Piperacillin-tazobactam is a widely used antibiotic. Although rare, thrombocytopenia related to piperacillin-tazobactam can be clinically significant. Drug-induced immune thrombocytopenia (DIIT) is difficult to distinguish from thrombocytopenia related to critical illness, infection, disseminated intravascular coagulation (DIC), or heparin-induced thrombocytopenia (HIT). We report a case of piperacillin-tazobactam-associated thrombocytopenia and review the literature to emphasize that negative antiplatelet antibody testing does not exclude this diagnosis. Case presentation: We report a 57-year-old woman with severe trauma and pulmonary infection who developed abrupt, severe thrombocytopenia after initiating piperacillin-tazobactam. The platelet count recovered rapidly after piperacillin-tazobactam was withdrawn. Coagulation parameters did not support overt DIC as the primary cause, and HIT was considered unlikely (4Ts score ≤3; no thrombosis on serial bedside ultrasonography). A Naranjo Adverse Drug Reaction Probability Scale score of 5 indicated a probable adverse drug reaction. Flow cytometric testing for anti-platelet antibodies was negative. Review: We identified 23 eligible reports. All patients were considered immune-mediated. Antiplatelet antibody testing was not performed on many patients; importantly, piperacillin-tazobactam-associated immune thrombocytopenia has also been suspected in cases with negative antibody results. Conclusion: This case and the reviewed literature highlight that negative platelet antibody testing does not exclude piperacillin-tazobactam-associated DIIT. A structured diagnostic approach and close platelet monitoring are warranted when DIIT is suspected in critically ill patients. Clinical evaluation and temporal association remain critical for diagnosis.