EBM Consult

Lab Test: Bilirubin, Total (Blood) Level

    Lab Test
    • Bilirubin, Total (Blood)
    • Measurement of total bilirubin in serum to evaluate liver function and bilirubin metabolism
    Reference Range
    • Adults:  0.3-1 mg/dL (5.1-17 micromol/L)
    • Premature infants, cord blood:  < 2 mg/dL (<34 micromol/L)
    • Premature infants, 0 to 1 day:  < 8 mg/dL (<137 micromol/L)
    • Premature infants, 1 to 2 days:  <12 mg/dL (<205 micromol/L)
    • Premature infants, 3 to 5 days:  <16 mg/dL (<274 micromol/L)
    • Neonates, cord blood:  <2 mg/dL (<34 micromol/L)
    • Neonates, 1 to 2 days:  1.4-8.7 mg/dL (24-149 micromol/L)
    • Neonates, 3 to 5 days:  1.5-12 mg/dL (26-205 micromol/L)
    • Children, 6 days to 18 years:  0.3-1.2 mg/dL (5-21 micromol/L)
    • Critical values:  Adult:  > 12 mg/dL Newborn:  >15 mg/dL (immediate treatment required to avoid kernicterus)
    Indications & Uses
    • Suspected biliary calculi in acute cholecystitis - the serum bilirubin level is elevated (usually to < 5 mg/dL) in up to one third of patients with cholelithiasis and may indicate the presence of biliary calculi.  Values typically return to normal within one week after symptoms resolve, unless suppuration ensues.  As a rule, direct hyperbilirubinemai predominates. 
    • Suspected biliary causes of pancreatitis - levels are raised in only 10% of patients with acute pancreatitis.  The increase is usually transient and without major clinical significance.  In chronic pancreatitis, elevated total bilirubin levels may be caused by coexisting liver disease or cholestatis due to compression of the distal common bile duct by an inflamed pancreatic head.
    • Suspected bilovenous fistula in blunt abdominal trauma - an excessively high serum total bilirubin, associated with only moderately elevated liver enzymes, may be seen in traumatic bilovenous fistula.  Endoscopic retrograde cholangiopancreatography (ERCP) is the most reliable method to localize the fistula, whereas CT o ultrasonography help localize and assess the extent of parenchymal injury.
    • Suspected hepatic dysfunction in rhabdomyolysis - About 25% of patients with rhabdomyolysis have reversible hepatic dysfunction (2.6 to 14.3 mg/dL).  Hyperbilirubinemia secondary to rhabdomyolysis associated with intravenous drug abuse and sock may be a consequence of hemolysis or hepatic underperfusion.
    • Suspected liver disease - total level ranging up to 20 mg/dL or higher may occur 3-5 months after viral exposure.  Jaundice or icterus is usually evident when the serum bilirubin level exceeds 2.5 mg/dL.  An elevation greater than 20 mg/dL suggests severe liver disease. 
    • In patients with hepatitis-induced acute liver failure, a serum total bilirubin level > 17.5 mg/dL (300 mmol/L) is a criterion for predicting death and the need for liver transplantation.  A low transaminase level associated with a high bilirubin level I the presence of chronic liver disease also indicates a poor prognosis.
    • Suspected liver dysfunction in ehrlichiosis - abnormal liver profiles and cytopenias are important clues to diagnosis of this disease, but the contribution of total bilirubin levels to diagnosis appears limited.  Only about 25% of ehrlichiosis patients have elevated total levels.  In contrast, focal hepatocellular necrosis typically induces mild to moderate elevations of AST (about 85% of patients), ALT (75% to 80%), and LDH in the first weeks of the illness.
    • Suspected liver dysfunction in Hb S (sickle cell) disease - sickle cell (SS) disease patients have baseline elevated levels of serum total (mean 2.5 mg/dL; range 1.5 to 4 mg/dL) and indirect bilirubin.  Increased hyperbilirubinemia above baseline without accompanying increased liver enzyme or direct bilirubin levels indicates marked hemolysis.  Hyperhemolytic crises typically occur following exposure to oxidant drugs or chemicals in patients with associated G-6-PD deficiency, but it also may occur during baso-occlusive crises. 
    • Serum total bilirubin levels (vs. baseline) in SS disease-associated hepotobiliary disorders include:
      • Nonobstructive cholelithiasis:  stable (at baseline)
      • Obstructive cholelithiasis:  markedly increased
      • Transfusion hepatitis:  increased
      • Acute hepatic crisis:  markedly increased
      • Transfusion hemosiderosis:  stable or slightly increased
    • Suspected or known bacterial septicemia - both hepatocellular dysfunction and increased red blood cell destruction may account for elevated levels in septic patients.  Hyperbilirubinemia (total bilirubin > 4 mg/dL) may be associated with organ dysfunction in severe sepsis.  Elevated levels suggest bacteremia with Bacteroides infection, hemolysis secondary to clostridial infection, or DIC.  Hyperbilirubinemia in patients with Staphylococcus aureus sepsis may portend a high risk of death from overwhelming sepsis.  Liver function tests should be obtained at baseline, because septic patients may subsequently develop hepatic dysfunction secondary to hypoperfusion (ie, shock liver).
    • Suspected Reye's syndrome - the total level is usually normal but may be mildly elevated.  If the total level is greater than 5 mg/dL, other diagnostic possibilities should be considered.
    • Suspected toxic shock syndrome - modest elevations of total levels occur in this syndrome, but are transient and non-specific.  The hyperbilirubinemia usually resolves within 1 to 2 weeks.
    • Suspected liver dysfunction in HIB infection - potential causes of increased bilirubin levels in HIB/AIDS include intrahepatic or extrahepatic malignancy, sclerosing cholangitis, papillary stenosis, and drug-induced hepatitis.
    Clinical Application

    Bile is formed in the liver and may constituents, including bilirubin.  Bilirubin metabolism begins with the breakdown of red blood cells (RBCs) in the reticuloendothelial system (mostly the spleen).  Hemoglobin is released from RBCs and broken down to heme and globin molecules.  Heme is then catabolized to form biliverdin, which is transformed to bilirubin.  This is unconjugated (indirect) bilirubin which is conjugated with a glucuronie molecule in the liver, resulting in conjugated (direct) bilirubin. 

    Total bilirubin measurement includes unconjugated (indirect), conjugated (direct), and delta (albumin-bound conjugated) bilirubin and usually are4 sufficient for clinical purposes (ie, fractionated bilirubins measurements are less accurate and unnecessary).

    Jaundice is the discoloration of body tissues caused by abnormally high blood levels of bilirubin.  Jaundice results from a defect in the normal metabolism or excretion of bilirubin.  This defect can occur at any stage of heme catabolism.

    Related Tests
    • Comprehensive metabolic panel
    • Hemolysis panel
    • Hepatic function panel
    • Transfusion reaction workup
    • Transplant panel
    • Liver enzymes such as alkaline phosphatase (ALP), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and 5'-nucleotidase.
    Drug-Lab Interactions
    • Drugs that may cause increased blood levels of total bilirubin include:  allopurinol, anabolic steroids, antibiotics, antimalarials, ascorbic acid, azathioprine, chlorpropamide (Diabinese), cholinergics, codeine, dextran, diuretics, epinephrine, meperidine, methotrexate, methyldopa,  monoamine oxidase inhibitors, morphine, nicotinic acid (large doses)m oral contraceptives, phenothiazines, quinidine, rifampin, salicylates, steroids, sulfonamides, theophylline, and vitamin A.
    • Drugs that may cause decreased blood levels of total bilirubin include barbiturates, caffeine, penicillin, and salicylates (high dose).
    Test Tube Needed
    • Marble top tube* (PDR), red top tube
    • Note that fasting requirements vary among different laboratories.  Some require keeping the patient on nothing by mouth (NPO) status after midnight the day of the test except for water.
    • Collect venous blood specimen.  Use a heel puncture for blood collection in infants.
    • Prevent hemolysis of blood during phlebotomy. 
    • Apply pressure or a pressure dressing to the venipuncture site and assess the site for bleeding.  Patients with jaundice may have prolonged clotting times.
    Storage and Handling
    • Avoid exposing specimen to light.  Prolonged exposure (over 1 hour) to sunlight or artificial light can reduce bilirubin content.
    • Do not shake the tube, because inaccurate test results may occur.
    What To Tell Patient Before & After
    • Explain the procedure to the patient.
    • LaGow B et al., eds. PDR Lab Advisor. A Comprehensive Point-of-Care Guide for Over 600 Lab Tests.  First ed. Montvale, NJ: Thomson PDR; 2007.
    • Pagana K, Pagana TJ eds. Mosby's Manual of Diagnostic and Laboratory Tests. 5th Ed.  St. Louis, Missouri. 2014.

MESH Terms & Keywords

  • Bilirubin, Total