Elevated Bilirubin in Aplastic Anemia and Heart Failure

Mechanisms and Clinical Implications

• Eryptosis (programmed red blood cell death) is enhanced in aplastic anemia, leading to accelerated clearance of circulating RBCs and increased bilirubin formation 1
• The increased loss of RBCs leads to increased formation of bilirubin, which can further trigger eryptosis by enhancing Ca²⁺ influx and ceramide production, creating a vicious cycle 1
• Heart failure causes passive congestion of the liver, which can impair liver function and bilirubin metabolism 2, 3
• Mild unconjugated hyperbilirubinemia is frequently observed in Fontan-associated liver disease (FALD) and other forms of heart failure 2, 3
• Hyperbilirubinemia in heart failure is multifactorial and results from a combination of liver impairment and passive congestion 2
• The pathophysiology of anemia in heart failure is multifactorial, including hemodilution, inflammation, and impaired erythropoietin production 4
• Patients with both aplastic anemia and heart failure experience enhanced eryptosis due to multiple triggers, including oxidative stress from heart failure and inflammatory cytokines (TNF-α and IL-6) in heart failure 4, 5
• Bilirubin metabolism can be divided into prehepatic, intrahepatic, and posthepatic phases, and prehepatic: Excessive bilirubin from hemolysis in aplastic anemia can overwhelm the liver's conjugation process, leading to unconjugated hyperbilirubinemia 6, 7
• Intrahepatic: Heart failure causes congestion that impairs hepatocyte function and bilirubin transport 2, 3
• The combination of aplastic anemia and heart failure creates a "double hit" to bilirubin metabolism 1, 2
• The presence of burr cells (echinocytes) on peripheral blood smear in these patients should prompt investigation of liver and kidney function 5
• Addressing the underlying causes of both conditions is essential for managing hyperbilirubinemia 4