From the Guidelines
Elevated bilirubin in sickle cell disease is primarily caused by increased red blood cell destruction (hemolysis), as stated in the most recent and highest quality study 1.
Causes of Elevated Bilirubin
The abnormal hemoglobin S in sickle cell disease causes red blood cells to become rigid and sickle-shaped, significantly shortening their lifespan from the normal 120 days to just 10-20 days. When these cells break down prematurely, hemoglobin is released and metabolized into bilirubin, overwhelming the liver's processing capacity. This results in unconjugated (indirect) hyperbilirubinemia, which can manifest as jaundice, scleral icterus, and dark urine.
Key Factors Contributing to Hyperbilirubinemia
- Increased red blood cell destruction (hemolysis) due to abnormal hemoglobin S
- Impaired liver function from chronic sickling in hepatic sinusoids
- Iron overload from blood transfusions
- Viral hepatitis from transfusion-related infections
Management of Hyperbilirubinemia in Sickle Cell Disease
Management focuses on treating the underlying sickle cell disease through:
- Hydration
- Pain control
- Hydroxyurea therapy
- Transfusions when necessary Rather than directly targeting the hyperbilirubinemia itself, as supported by 1, the most recent study, which provides the highest quality evidence for the management of sickle cell disease.
Additional Considerations
Other studies, such as 1, 1, 1, and 1, provide additional context and support for the management of sickle cell disease, but the most recent and highest quality study 1 takes precedence in guiding clinical decision-making.
From the Research
Causes of Elevated Bilirubin in Sickle Cell Disease
- Chronic hemolysis and ineffective erythropoiesis are the primary sources of hyperbilirubinemia in sickle cell disease, as suggested by the correlation between bilirubin and lactate dehydrogenase levels 2
- Elevated bilirubin excretion can lead to the formation of black pigment gallstones, which are common in patients with sickle cell disease 2
- Liver disease, such as hepatitis and hemosiderosis, can also contribute to elevated bilirubin levels in some patients with sickle cell disease 2, 3
- Certain medications, like ceftriaxone, can cause direct hyperbilirubinemia in patients with sickle cell disease, particularly those with chronic liver chemistry abnormalities 4
- The abnormal hemoglobin in sickle cell disease can lead to increased hemolysis, which in turn can cause elevated bilirubin levels 5
- Chronic inflammation and oxidative stress, which are characteristic of sickle cell disease, can also contribute to the development of complications, including elevated bilirubin levels 6
Mechanisms of Hyperbilirubinemia
- Intrasinusoidal sickling and Kupffer cell erythrophagocytosis are common findings in liver biopsies of patients with sickle cell disease, and can contribute to liver dysfunction and elevated bilirubin levels 3
- The accumulation of hemoglobin and heme in the plasma can decrease nitric oxide bioavailability and enhance the production of reactive oxygen species, leading to chronic vasculopathy and complications, including elevated bilirubin levels 6
- The release of microparticles from various cellular origins can participate in the inflammation and oxidative stress in sickle cell disease, further altering red blood cell properties and contributing to elevated bilirubin levels 6