31-year-old homeless male, Jehovah’s Witness, with a history of sickle cell disease (admitted 1 month prior for pain crisis), presented with 2 days of lower back and lower extremity pain. His presenting BUN was 62 mg/dL, Creatinine 2.93 mg/dL, Total Bilirubin 5.9 mg/dL, and Hemoglobin 3.7 g/dL with a Hemoglobin S fraction of 95%; transfusions were deferred secondary to religious beliefs. During his admission, vital signs remained stable, but his pain became difficult to control on IV narcotics, along with worsening jaundice, epistaxis, and anuria. After repeated discussions of risk versus benefit, the patient agreed to blood product transfusion; subsequent labs showed a Total Bilirubin of 76 mg/dL (Direct fraction of 65 mg/dL), PT 36 sec, aPTT 172 sec, INR 3.3, Creatinine 5.4 mg/dL, with AST 83U/L, ALT 25U/L, and GGT 140U/L. Viral hepatitis and autoimmune panel were negative. A non-contrast abdominal MRI showed cholelithiasis, new cirrhosis, and biliary ductal dilation with an 8-mm stone in the common bile duct. He received 15-units of packed red blood cells, fresh frozen plasma, and prothrombin complex concentrate, as well as exchange transfusion twice, which improved his anemia and decreased his HbS fraction to 7%. However, his symptoms persisted, including requiring medical intensive care unit transfer for urgent hemodialysis due to uremic bleeding. Despite extensive therapy, his liver failure progressed to overt coagulopathy with multiple subdural bleeds, multi-organ failure, and eventual death.
Discussion:
Sickle cell disease (SCD) is a common hematologic condition but its hepatic manifestations (under the umbrella term “sickle cell hepatopathy”) pose particularly significant challenges. Our patient had Sickle Cell Intrahepatic Cholestasis (SCIC), a rare (only about 50 reported cases) but fatal condition, thought to arise from deformed red blood cell adhesion to the hepatic vascular endothelium, leading to congestion and tissue ischemia. Liver biopsy is a relative contraindication in active sickle crisis but direct bilirubin is a mortality predictor. Numerous case reports have advocated early & aggressive exchange transfusion, sometimes for several months before clinical improvement. Currently, the role of liver transplantation is not clearly defined. Of note, hydroxyurea, which our patient was not taking, decreases pain crises but does not affect hepatic sequestration or overall mortality.
Conclusions:
Our case presentation highlights SCD-induced acute liver failure and the vast differential diagnosis that can delay care and increase mortality risk. Often, hospitalists care for such patient populations during sickle crises and complications, and so should have a high index of suspicion. Although limited evidence shows the benefit of exchange transfusion in these instances, as our case demonstrates, this is unfortunately a condition that carries a high mortality.