Successful Exchange Transfusions in a Patient With Sickle-Beta Thalassemia Having Recurrent Episodes of Liver Failure From Intrahepatic Cholestasis

Abstract

Sickle cell intrahepatic cholestasis (SCIC) is a rare and often fatal manifestation of sickle cell disease. Microvascular and sinusoidal occlusion from sickling RBCs results in bile canalicular cholestasis with ballooning hepatocytes and hyperbilirubinemia often progressing to acute liver failure and death. Previous case reports have shown mixed success with early exchange transfusion with a goal of hemoglobin S (HgbS) < 30%. We present the first case report of a patient with sickle-beta thalassemia who was successfully treated on three seperate occasions with exchange transfusion for intrahepatic cholestasis liver failure. A 44 year-old African American female with sickle cell-β° thalassemia and pulmonary hypertension presented with acute lower extremity pain, fatigue, scleral icterus and fever. A previous liver biopsy showed moderate portal chronic inflammation (Figure 1A), mild sinusoidal and portal fibrosis (Figure 1B), marked sinusoidal dilatation with RBCs (Figure 1C), and mild iron accumulation in Kupffer cells. She denied recent use of alcohol or acetaminophen. She was altered with jaundice, asterixis and clonus on exam. Abdomen was soft and non-tender without hepatosplenomegaly or ascites. Abdominal ultrasound showed hepatopetal flow without biliary dilatation. Labs notable for total bilirubin 68.0 (conjugated 38.0 mg/dL), AST/ALT 191/51 U/L, INR 2.8 and platelets 186 x103/μL. Anemia stable at Hgb of 7.8 g/dL. HgbS of 44.1%. She had leukocytosis, elevated creatinine and evidence of hemolysis. Blood and urine culture and viral studies were negative. Her liver failure was felt secondary to SCIC and she was emergently treated with exchange transfusion. Her post-exchange HgbS dropped to 17.1%, bilirubin downtrended, coagulopathy reversed, and her mental status cleared. She was discharged 3 days later in her regular state of health. Over the next 15 months she presented with two additional episodes of liver failure from SCIC that each resolved with a single exchange transfusion (Figure 2). To the best of our knowledge, this is the only case of a sickle-beta thalassemia patient presenting with multiple, distinct episodes of liver failure SCIC successfully treated with exchange transfusion. Although her extensive comorbidities precluded liver transplant, the success of exchange transfusion in SCIC liver failure may provide a bridge to definitive therapies such as stem cell and/or liver transplant for sickle cell patients in the future.Figure: Prior liver biopsy demonstrating moderate portal chronic inflammation (A), sinusoidal and portal fibrosis (B) and marked diffuse sinusoidal dilatation (C) with red blood cells.Figure: Labs during the three separate acute liver failure episodes. Bold line between Day 0 and Day 1 indicates exchange transfusion performed. AST, aspartate aminotransferase; ALT, alanine aminotransferase; INR, international normalized ratio; mg, milligrams; g, grams; dL, deciliter; L, liter.