Differentials
Hemolysis
SIGNS / SYMPTOMS
Signs and symptoms of anemia (fatigue, dizziness, dyspnea, pallor, tachycardia). Gallstones. Splenomegaly may be present in some causes of hemolysis (hereditary spherocytosis, non-Hodgkin lymphoma, or portal hypertension due to cirrhosis). However, GS may coexist with hereditary hemolytic anemias.[3]
INVESTIGATIONS
CBC: abnormal.
Peripheral smear: abnormal.
Reticulocyte count: abnormal.
Lactate dehydrogenase: elevated (normal in GS).
Cirrhosis
SIGNS / SYMPTOMS
Patients with liver disease often have hepatomegaly, splenomegaly, spider angiomas, palmar erythema, encephalopathy, and gynecomastia.
INVESTIGATIONS
Ultrasound: may show hepatomegaly, splenomegaly, and sluggish or retrograde portal vein flow.
CBC: thrombocytopenia and anemia.
Clotting profile: coagulopathy.
Liver aminotransferases: usually elevated.
Alkaline phosphatase: elevated.
Gamma-glutamyltransferase (GGT): elevated.
Cardiac disease (e.g., congenital heart disease and valvular heart disease)
SIGNS / SYMPTOMS
Clubbing, heart murmur, shortness of breath, palpitations, orthopnea, paroxysmal nocturnal dyspnea.
INVESTIGATIONS
Echocardiogram: abnormal.
Abdominal ultrasound: dilated inferior vena cava and hepatic and portal vessels.
Liver aminotransferases: elevated.
Biliary tract disease
SIGNS / SYMPTOMS
Pruritus, acholic (pale) stools, bilirubinuria.
INVESTIGATIONS
Imaging: abnormal bile ducts.
Alkaline phosphatase: elevated.
GGT: elevated.
Liver aminotransferases: elevated.
Thyrotoxicosis
SIGNS / SYMPTOMS
Tremor, palpitations, tachycardia, diaphoresis, diarrhea.
INVESTIGATIONS
Thyroid-stimulating hormone: decreased.
Serum-free T4: elevated.
Serum-free T3: elevated.
Rhabdomyolysis
SIGNS / SYMPTOMS
Myalgia, arthralgia, weakness.
INVESTIGATIONS
Creatine phosphokinase: elevated.
Blood urea nitrogen (BUN) and creatinine: possibly elevated.
Crigler-Najjar syndrome type I
SIGNS / SYMPTOMS
Severe jaundice within the first few days of life.
Kernicterus or neurologic deficits.
Life expectancy <1 year.
INVESTIGATIONS
Bilirubin level: usually >20 mg/dL because of absent bilirubin conjugation.
Crigler-Najjar syndrome type II
SIGNS / SYMPTOMS
Bilirubin encephalopathy, though rare, can be induced by factors such as infection or anesthesia.
Usually presents in childhood.
INVESTIGATIONS
Bilirubin level: generally between 6 and 25 mg/dL because of a uridine-diphosphoglucuronate glucuronosyltransferase (UDPGT) enzyme activity <10%.
Medication-induced hyperbilirubinemia
SIGNS / SYMPTOMS
Numerous (e.g., edema, ataxia, nausea, vomiting).
Review of patient’s medication list: for example, rifampin, acetaminophen overdose, sulfasalazine, methyldopa, erythromycin, or estrogens may cause hyperbilirubinemia.[14]
INVESTIGATIONS
Liver aminotransferase: usually elevated with medications such as rifampin or probenecid. Abnormalities should improve after withdrawal of the offending agent.
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