Piperacillin-Induced Immune Hemolysis Presenting with Tachycardia and Cardiac Arrest

Abstract

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.

Risk of piperacillin‐induced hemolytic anemia in patients with cystic fibrosis and antipseudomonal treatment: a prospective observational study

“…This is also supported by the results in the present study. Furthermore, repeated exposure to the same drug has been suggested to be important in the antibody formation process and DIIHA development . The latter findings are in line with the results of this study.…”

“…The onset and the severity of PIHA are variable and may occur within 1 to 14 days after initiating piperacillin or piperacillin/tazobactam therapy. Hemoglobin frequently decreases to 3‐5 g/dL or even lower levels and results in fatalities in up to 6% of cases . Therefore, PIHA has been regarded as a highly acute and life‐threatening event, particularly if it remains undetected in due time.…”

“…Previous case reports and case series suggest a higher incidence of DIIHA due to piperacillin in patients with CF compared to the general patient population. Indeed, more than 50% of the reported cases of piperacillin‐induced hemolytic anemia (PIHA) were observed in patients with CF . PIHA is usually characterized by acute intravascular hemolysis due to complement activation .…”

A case of extravascular hemolysis with Tk‐activation

“…Lastly, the number of reports of hemolysis with Zosyn ® (piperacillin/tazobactam) is increasing lately. Antibodies to piperacillin or piperacillin/tazobactam have been reported to cause both intra and extravascular hemolysis . Our patient received one dose of Zosyn ® on hospital day 1.…”

A new onset of thrombocytopenia and microangiopathic hemolytic anemia in the healthcare setting: A challenge for diagnosis

“…Clindamycin, piperacillin/tazobactam, and sulfamethoxazole/trimethoprim can all lead to thrombocytopenia, while hemolytic anemia is rare with the use of clindamycin. Anemia associated with piperacillin/tazobactam (mainly piperacillin) is through a different mechanism (autoimmune) from MAHA . Although the use of sulfamethoxazole/trimethoprim has been reported to cause MAHA, the patient did not develop thrombocytopenia and MAHA until 14 days after the use, which would be atypical timing.…”