Piperacillin-Induced Immune Hemolytic Anemia Masked by Intestinal Failure-Associated Liver Disease: A Case Report with Three Serial Exposures

Background: Drug-induced immune hemolytic anemia (DIIHA) secondary to piperacillin has an estimated incidence of 0.01–0.10% [1,2]. In patients with intestinal failure-associated liver disease (IFALD), chronic conjugated hyperbilirubinemia obscures typical hemolytic markers [3,4]. Case Presentation: A 27-year-old woman with traumatic short bowel syndrome requiring total parenteral nutrition for 6 months, IFALD (baseline total bilirubin 2.5 mg/dL), and chronic kidney disease experienced three piperacillin-tazobactam exposures over two months. First exposure (12 days): hemolysis developed after drug discontinuation (primary sensitization). Second exposure: severe hemolysis occurred within 3 days (anamnestic response) with hemoglobin declining to 5.8 g/dL, undetectable haptoglobin, elevated LDH, reticulocytosis, and strongly positive DAT (IgG 3+, C3d negative). Total bilirubin remained stable at 9.7 mg/dL despite severe hemolysis. Peripheral smear showed spherocytes and polychromasia without schistocytes. Naranjo score was 10 (definite causality) [5]. Treatment included drug discontinuation, corticosteroids, and transfusion with resolution within 8 days. Third exposure (6 days): no hemolysis occurred. At 5-month follow-up, hemoglobin returned to baseline at 9.7 g/dL. Conclusions: When baseline cholestasis masks unconjugated bilirubin elevation, diagnosis requires non-bilirubin hemolytic markers, peripheral smear, and positive IgG DAT. Immediate drug discontinuation is essential, with favorable prognosis in most cases.