Causes of mostly unconjugated hyperbilirubinemia

Bilirubin overproduction

Extravascular hemolysis

Extravasation of blood into tissues

Hypersplenism

Intravascular hemolysis

Inherited red blood cell disorders

Glucose-6-phosphate dehydrogenase deficiency*

Sickle cell disease*

Thalassemia

Hereditary spherocytosis

Hereditary elliptocytosis

Infection – Malaria, bacterial sepsis*

Autoimmune hemolytic anemia

Microangiopathic hemolytic anemia

Drug-induced hemolytic anemia (eg, cephalosporins, penicillins, trimethoprim-sulfamethoxazole)^¶

Impaired hepatic bilirubin uptake

Heart failure

Portosystemic shunts

Some patients with Gilbert syndrome

Certain drugs – Rifamycin, probenecid, flavaspadic acid, bunamiodyl

Impaired bilirubin conjugation

Inherited

Crigler-Najjar syndrome

Gilbert syndrome*

Acquired

Neonates – Physiologic hyperbilirubinemia*, breast milk jaundice*

Hyperthyroidism (mechanism unclear)

Certain drugs – Ethinyl estradiol, gentamicin (above therapeutic range), novobiocin, antiretroviral drugs

Liver diseases

Chronic persistent hepatitis

Advanced cirrhosis

Wilson disease

* Common causes.

¶ Refer to UpToDate content on drug-induced hemolytic anemia.

Data from: Mandl KD. Jaundice-Unconjugated hyperbilirubinemia. In: Textbook of Pediatric Emergency Medicine, Fleisher GR, Ludwig S, Henretig FM (Eds), Lippincott Williams and Wilkins, 2006. p.400.

Graphic 66972 Version 8.0

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Causes of mostly unconjugated hyperbilirubinemia