Marie Chartier, DVM, DACVIM, VCA Roberts Animal Hospital, Hanover, Massachusetts

ArticleLast Updated May 20231 min readPeer Reviewed
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Following are differential diagnoses for patients presented for hyperbilirubinemia.

Prehepatic Causes (Hemolysis) 

  • Idiopathic (primary) immune-mediated hemolytic anemia 

  • Secondary immune-mediated hemolytic anemia 

    • Infectious disease 

    • Drug- or vaccine-induced  

    • Paraneoplastic 

  • Nonimmune hemolysis  

    • Toxin (eg, zinc, onion) 

    • Erythrocyte fragmentation/microangiopathic anemia (caval syndrome, disseminated intravascular coagulation [DIC], vasculitis)  

    • Envenomation  

    • Metabolic (hypophosphatemia)  

    • Alloimmune (blood transfusion, neonatal isoerythrolysis [cats]) 

    • Breed-specific erythrocyte membrane or enzyme defects (eg, increased osmotic fragility [Somali, Abyssinian, and Siamese cats], stomatocytosis [Alaskan malamute, Drentsche Patrijshond, and miniature schnauzer], phosphofructokinase deficiency [English springer spaniel, Abyssinian, and Somali cat])  

Hepatic Causes (eg, Hepatocellular Dysfunction, Cholestasis)

  • Toxic or drug hepatopathy 

  • Inflammatory or infectious hepatopathy (eg, immune-mediated or infectious hepatitis, cholangiohepatitis, leptospirosis, cytauxzoonosis [cats], FIP)  

  • Hepatic lipidosis (cats) 

  • Neoplasia   

  • Fibrosis

Posthepatic Causes (eg, Cholestasis, Defective Biliary Excretion)

  • Biliary  

    • Gallbladder mucocele 

    • Cholelithiasis 

    • Stricture 

    • Infectious or inflammatory cholecystitis/cholangitis 

    • Neoplasia (gallbladder, bile duct) 

  • Extrabiliary 

    • Pancreatitis 

    • Neoplasia (pancreas, duodenum, regional lymph nodes) 

    • Proximal duodenal obstruction (eg, mass or foreign body causing secondary bile duct obstruction) 

    • Bile peritonitis (ie, gallbladder or common bile duct rupture)   

    • Septicemia (eg, cytokine-mediated cholestasis, downregulation of bilirubin transport receptors)  

Other Causes

  • Spurious (eg, artifact due to lipemia or hemolysis)