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 The platelet count recovered rapidly after piperacillin–tazobactam was withdrawn.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.