S5529 Zieve’s Syndrome: A Rare Cause of Hemolytic Anemia in Chronic Alcohol Use – A Case Report

Introduction: Zieve’s syndrome is an uncommon but clinically important triad of jaundice, hemolytic anemia, and hyperlipidemia that occurs in the setting of chronic alcohol use and underlying liver disease. Due to its episodic nature and clinical similarity to other hepatic conditions, it is often misdiagnosed or overlooked. Prompt identification is critical to avoid unnecessary testing and guide appropriate management focused on alcohol cessation and supportive care. Case Description/Methods: A 38-year-old woman with a history of daily alcohol intake presented with chest pain and melena. Physical examination showed scleral icterus and right upper quadrant tenderness. Initial labs revealed hemoglobin 7 g/dL, total bilirubin 2.0 mg/dL (direct 0.8 mg/dL), and alkaline phosphatase 157 IU/L. Computed tomography abdomen showed nodular cirrhosis. Esophagogastroduodenoscopy revealed grade 1 esophageal varices. She was transfused and discharged. Four months later, she returned with nausea, abdominal pain, tremors, and pruritus. Repeat labs demonstrated hemoglobin 7.1 g/dL, total bilirubin 6.5 mg/dL (direct 1.9), aspartate aminotransferase 88 U/L, alanine aminotransferase 37 U/L, and a markedly elevated reticulocyte index (21%). Hemoglobinuria and low haptoglobin (<30 mg/dL) were present. Direct Coombs test was negative. Peripheral smear showed macrocytosis, anisopoikilocytosis, and polychromasia. Imaging revealed hepatosplenomegaly. The constellation of hemolytic anemia, jaundice, chronic alcohol use, and laboratory findings confirmed Zieve’s syndrome. Discussion: Although first described in 1957, Zieve’s syndrome remains under-recognized, with fewer than 200 reported cases. Its pathophysiology involves alcohol-induced hepatocellular damage, erythrocyte membrane instability, and altered lipid metabolism. Diagnosis is primarily clinical and relies on identifying hemolysis in the context of alcohol use and liver disease. Hyperlipidemia, while classic, may be transient or absent at presentation, complicating diagnosis. This patient exhibited the core features of the syndrome during 2 separate admissions, underscoring the risk of recurrence and the importance of ongoing abstinence. Recognition of this reversible condition can prevent unnecessary interventions and enable prompt supportive care.