Medical Director Surgical ICU Cleveland Clinic Foundation
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Introduction: Severe thrombocytopenia in transplant patients has a broad differential that includes infection, graft rejection, portal hypertension, immunosuppressive side effects, heparin-induced thrombocytopenia (HIT), and drug reactions. Diagnostic evaluation is often complex due to overlapping clinical factors and the risk of rapid deterioration. Ceftaroline is a fifth-generation cephalosporin used for multidrug-resistant gram-positive infections. Although rare, it has been associated with drug-induced thrombocytopenia. We report a case of ceftaroline-associated thrombocytopenia in a critically ill transplant recipient confirmed with drug-dependent platelet antibody testing.
Description: A 75-year-old woman with alcoholic cirrhosis and membranous nephropathy, status post simultaneous liver-kidney transplant, was admitted one-year post-transplant with fever and weakness. She developed MRSA bacteremia unresponsive to vancomycin and was transitioned to ceftaroline on hospital day 7. Heparin infusion was initiated on day 8 for atrial fibrillation with rapid ventricular response. On day 13, her platelet count fell precipitously from 296K to 139K, then to 5K within 17 hours. Other blood counts remained stable. Citrated platelet counts confirmed the drop, and PF4 testing was negative. Ceftaroline was discontinued and replaced with vancomycin and clindamycin. IVIG was initiated. Drug-dependent platelet antibody testing later returned positive for ceftaroline. Her platelet count recovered within days, and she was discharged home with a ceftaroline allergy noted in her medical record.
Discussion: This case highlights the importance of considering rare causes of drug-induced thrombocytopenia in transplant patients, especially when common diagnoses such as HIT have been excluded. The rapid decline in platelet count, lack of pancytopenia, and recovery after cessation of ceftaroline supported a drug-related etiology. Confirmatory antibody testing strengthened the diagnosis. Intensivists should remain vigilant for this rare but serious complication, particularly in immunosuppressed patients with complex infections receiving broad-spectrum antibiotics.