Piperacillin-Induced Immune Hemolysis Presenting with Tachycardia and Cardiac Arrest

A 20-year-old nonverbal patient with profound developmental disabilities was treated with intravenous piperacillin-tazobactam for respiratory infection. After 8 days, he became afebrile with normal pulmonary status, but his pulse remained inexplicably rapid (114/minute). Investigations revealed severe normochromic normocytic hemolytic anemia (hemoglobin: 40 g/L, reticulocytes: 9.4%, nucleated erythrocytes: 5%). While being hospitalized, patient experienced sudden cardiac arrest from which he was successfully resuscitated. He had no blood loss or intrinsic heart disease to explain the acute anemia or cardiac arrest. He had uneventfully received piperacillin-tazobactam on 7 occasions during the preceding 5 years for >50 days. Patient was treated with intravenous crystalloids, methylprednisolone and transfusion of 3 units of packed erythrocytes. Piperacillin-tazobactam was discontinued. A direct antiglobulin test was positive for immunoglobulin G and complement. Antibody to piperacillin was detected in patient's serum by the "immune-complex" method confirming "piperacillin-induced immune hemolytic anemia (PIHA)". On discharge (day 15), patient's hemoglobin improved to 115 g/L (baseline: 131 g/L). Vigilant clinical and hematological monitoring for anemia is indicated in piperacillin-treated patients, particularly in those unable to verbalize their discomfort. Repeated piperacillin exposure may sensitize and predispose patients to PIHA.