EBM Consult

Lab Test: Bilirubin, Unconjugated, Indirect (Serum) Level

    Lab Test
    • Bilirubin, Unconjugated, Serum  (Indirect)
    • Measurement of unconjugated bilirubin levels in blood for the evaluation and management of hematologic hepatic, or biliary dysfunction. It is part of the evaluation of adult patients with hemolytic anemias and newborns with jaundice.
    Reference Range
    • Adult/elderly/child:  0.2-0.8 mg/dL or 3.4-12.0 mmol/L (SI units)
    Indications & Uses
    • Sickle cell disease - baseline elevations of indirect serum bilirubin in levels occur secondary to chronic hemolysis in sickle cell disease.  Steady state levels are typically 2.3 ± 1.9 mg/dL.  A relative increase in the baseline hyperbilirubinemia without change in direct bilirubin levels suggests increased red cell destruction, as found in hyperhemolytic sickle cell crisis.  A relative decrease in baseline hyperbilirubinemia can occur I painful sickle crises, suggesting other causes of anemia than hemolysis such as aplastic or sequestration crisis. 
    • Suspected biliary obstruction - elevated bilirubin and alkaline phosphatase are consistent with biliary obstruction or cholangitis.  Serum bilirubin levels are elevated in 8% to 37% of cases of cholecystitis, usually to less than 5 mg/dL (less than 85.5 micromol/L) and the higher the bilirubin level, the more likely that stones will be present in the common duct.
    • Suspected Crigler-Majjar syndrome type I or II - unconjugated hyperbilirubinemia due to a severe deficiency of uridine diphosphate glucuronosyltransferase is seen in this syndrome.  In type II, serum bilirubin levels are rarely in excess of 20 mg/dL, while type I is more severe and is often accompanied by kernicterus shortly after birth.
    • Suspected Gilbert's syndrome - unconjugated hyperbilirubinemia, in the absence of liver disease and hemolysis, that increases 2 to 3 times when an individual is placed on a 400 kcal diet for 3 days is consistent with Gilbert's syndrome.
    • Suspected neonatal physiologic jaundice - indirect bilirubin levels peaking in the first days of life at approximately 5 to 6 mg/dL in full-term neonates (up to the first week of life for preterm and some Asian neonates), then declining over several weeks, are consistent with physiologic jaundice.  Indirect bilirubin levels exceeding 17 mg/dL in full-term infants may indicate a cause other than physiologic jaundice. 
    • Physiologic jaundice appears in full-term infants after the first 124 hours of life, peaking on day 4 or 5 of life, while physiologic jaundice in preterm infants does not appear until 48 hours after birth, lasting up to 2 weeks.  Suspected pyloric stenosis - indirect bilirubin levels are elevated in 2% to 3% of infants with this.  Levels may reach 5 to 10 mg/dl but rarely exceed 20 mg/dL.
    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. 

    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. 

    Conjugated and unconjugated bilirubin are separated out when "fractionation or differentiation" of the total bilirubin to its direct and indirect parts is request4ed from the laboratory.  Normally the unconjugated bilirubin makes up 70% to 85% of the total bilirubin. 

    Unconjugated bilirubin is protein-bound.  Routine exams generally measure total bilirubin, which may then be broken down into unconjugated and conjugated.  Unconjugated results may not be reported by all laboratories. 

    Increased blood levels:

    • Erythroblastosis fetalis, transfusion reaction, sickle cell anemia, hemolytic jaundice, hemolytic anemia, pernicious anemia, large-volume blood transfusion, resolution of large hematoma - RBC destruction occurs.  Large amounts of heme are available for catabolism into bilirubin.  This quantity exceeds the liver's capability to conjugate bilirubin.  Indirect bilirubin levels rise.
    • Hepatitis, cirrhosis, sepsis, and neonatal hyperbilirubimenia - the diseased, injured, or immature liver cannot conjugate the bilirubin presented to it.  Indirect bilirubin levels rise.
    • Crigler-Najjar syndrome and Gilbert syndrome - congenital enzyme deficiencies interrupt conjugation of bilirubin.  Indirect bilirubin levels rise.

    Results are increasing in prolonged fasting. 

    Related Tests
    • Liver enzymes such as alkaline phosphatase (ALP), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and 5'-Nucleotidase - all helpful in the evaluation of the liver.
    • Complete blood cell count, haptoglobin, and other blood tests - helpful in the evaluation of hemolytic anemias.
    • Comprehensive metabolic panel
    • Transfusion reaction workup
    • Transplant panel
    Drug-Lab Interactions
    • Bloodhemolysis and lipemia can produce erroneous results.
    Test Tube Needed
    • Red top tube
    • Collect a venous blood sample (5 mL).
    • Use a heel puncture for blood collection in infants.
    • Prevent hemolysis of blood during phlebotomy.
    • Do not shake the tube, because inaccurate test results may occur.
    • 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
    • Protect the blood sample from bright light and sunlight.  Prolonged exposure (over 1 hour) to sunlight or artificial light can reduce bilirubin content.
    • Refrigerate sample.
    What To Tell Patient Before & After
    • Explain the procedure to the patient.
    • 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.
    • Pagana K, Pagana TJ eds. Mosby's Manual of Diagnostic and Laboratory Tests. 5th Ed.  St. Louis, Missouri. 2014.

MESH Terms & Keywords

  • Bilirubin, Unconjugated, Indirect