Sickle cell disease (SCD) is a multisystem disorder characterized by recurrent vaso-occlusive events and progressive organ damage. Among its chronic complications, sickle hepatopathy, driven by sinusoidal obstruction, ischemia, and cholestasis, remains underrecognized despite its major prognostic significance. During acute crises, hepatic dysfunction may amplify systemic inflammation, impair metabolic reserve, and precipitate rapid multiorgan failure. We report the case of a 28-year-old man with homozygous SCD and biopsy-confirmed chronic hepatic vaso-occlusive disease who presented after discontinuation of hydroxyurea with severe hemolysis, profound hyperbilirubinemia (total bilirubin 59 mg/dL), and anemia. Shortly after admission, he developed acute hypoxemic respiratory failure with new bilateral pulmonary infiltrates consistent with acute chest syndrome (ACS). Despite aggressive supportive management, including red blood cell transfusion, corticosteroids, and plasma exchange (PLEX) for worsening hemolysis and coagulopathy, his condition rapidly deteriorated, with progressive metabolic acidosis, disseminated intravascular coagulation, and hepatorenal failure. Exchange transfusion was deemed unsafe due to critically low hemoglobin (2.3 g/dL), and both extracorporeal membrane oxygenation and urgent liver transplantation were contraindicated. The patient died less than 24 hours after admission to the ICU. This case highlights the fulminant and often fatal interaction between advanced sickle hepatopathy and ACS. Chronic hepatic dysfunction compromises cytokine clearance, exacerbates endothelial injury, and reduces physiological resilience, thereby increasing vulnerability to hyperhemolysis and multiorgan failure. While PLEX has been proposed as a rescue therapy in severe hyperhemolysis or hepatic vaso-occlusive crisis, evidence remains limited, and outcomes are poor once profound acidosis and systemic collapse ensue. In patients with SCD and preexisting hepatic disease, the development of ACS should prompt immediate multidisciplinary escalation and early consideration of exchange transfusion before irreversible organ dysfunction occurs. This case underscores that sickle hepatopathy is a dynamic, high-risk condition that critically influences outcomes during acute SCD crises.
Prada et al. (Fri,) studied this question.