- Red top, tiger top or green top tube
- 2 capillary tubes in newborns
- 3-5 mL Venous blood (or capillary tubes as above)
Additional information:
- In infants, blood is obtained by heelstick. Microcapillary tube is filled with blood up to the required level.
- Adults - fasting for at least 4 hrs.
- Protect sample from direct sunlight and UV light.
- Bilirubin is a byproduct formed in the liver, spleen, and bone marrow due to the breakdown of the heme protein in red blood cells.
- Bilirubin is the predominant pigment secreted in the bile which then enters the intestines and gives stool its normal brown color.
- Normally only a small amount of bilirubin circulates in the blood.
- Total bilirubin is constituted by indirect (unconjugated) and direct (conjugated) bilirubin.
Total bilirubin is the indirect added to the direct bilirubin.
Indirect (Unconjugated) bilirubin is insoluble bilirubin that is in the blood stream that gets delivered to the liver to be changed into direct (Conjugated) bilirubin by the liver.
When bilirubin is not adequately metabolized (or is produced very quickly as in hemolytic diseases); jaundice, or a yellow coloration to the skin and eyes will occur. Other symptoms will be pale colored stool and dark urine.
The test is useful for:
- Differential diagnosis of jaundice
- Evaluation of biliary disease
- Evaluation of liver function
- Monitoring newborn jaundice & the effects of phototherapy on newborn jaundice
- Monitoring the effect of drugs on liver function
Additional information:
- The breakdown of the red blood cells by the reticuloendothelial system produces indirect (free or unconjugated) bilirubin, which is lipid soluble. In the presence of the enzyme glucuronyl transferase, it is converted in the liver to mono and diglucoronides, and excreted in bile in it's water soluble conjugated (direct or bound) form.
- The measurements of total bilirubin and the direct bilirubin levels are done directly from the blood. The indirect bilirubin levels are obtained from the total and direct bilirubin measurements.
- An increased serum bilirubin level is termed as hyperbilirubinemia
- Hyperbilirubinemia may be seen due to:
- Blockage of the biliary tract
- Decreased conjugation by the liver
- Decreased secretion into the bile
- Increased production of bilirubin
- Unconjugated hyperbilirubinemia occurs due to increased production or decreased conjugation of the bilirubin
- Conjugated hyperbilirubinemia is due to obstruction to the biliary flow
- The most common clinical sign of hyperbilirubinemia is jaundice.
- Neonatal jaundice is seen in about 60% of all term newborns and 80% of preterm newborns within 3 days of birth. It may be classified as:
- Physiologic jaundice
- In healthy, full term infants
- Total serum bilirubin usually peaks to 5-12 mg/dL on the second or third day after birth
- Nonphysiologic jaundice
- Occurs >24hr after birth
- Bilirubin rises faster than 0.5 mg/dL per hour or 5 mg/dL per d
- Total bilirubin >15 mg/dL in a full term infant
- Total bilirubin >10 mg/dL in a preterm infant
- Evidence of acute hemolysis
- Hyperbilirubinemia beyond 10 days in a full term infant
- Hyperbilirubinemia beyond 21 days in a preterm infant
- When the bilirubin level rises to greater than 20 mg/dL, in the newborn, it may lead to bilirubin encephalopathy with diffuse neuronal damage and staining of the basal ganglia (Kernicterus); this requires specific therapy; typically initially with UV lights
- Related laboratory tests include:
1-antitrypsin/phenotyping- Alanine aminotransferase
- Albumin
- Alkaline phosphatase
- Ammonia
- Amylase
- Anti-smooth muscle antibody
- Aspartate aminotransferase
- Cholesterol
- Coagulation factor assays
- Complete blood count
- Copper
-glutamyltransferase- Hepatitis serologies
- Infectious mononucleosis screen
- Lipase
- Liver biopsy
- Protein
- Prothrombin time
- Urinalysis
Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.
| Conv. units (mg/dL) | SI units (µmol/L) | |
|---|---|---|
| Total bilirubin | ||
| >1 month - Adult | 0.1–1.2 | 2–20 |
| Neonates | ||
| <1 day | 1.5-9 | 26-154 |
| 1-2 days | 3-12 | 51-205 |
| 3-5 days | 2-12 | 34-205 |
| Direct bilirubin | <0.5 | <8.6 |
| Indirect bilirubin | <1.1 | <19 |
Critical Values:
In neonates, urgent therapy is typically recommended (UV lights &/or exchange transfusion) when total bilirubin level =15 mg/dL (SI 257 µmol/L); especially where there is anticipated to be further rise in the bilirubin.
I. Unconjugated hyperbilirubinemia is seen in the following conditions:
a) Increased bilirubin production:
- ABO incompatibility
- Dyserythropoiesis
- G-6-PD deficiency
- Pyruvate kinase deficiency
- Spherocytosis
- Erythroblastosis fetalis
- Hematoma
- Hemolytic anemia
- Late pregnancy administration of sulfa drugs to the mother (jaundice in the newborn)
- Pernicious anemia
- Polycythemia
- Post-blood transfusion period:
- Rapidly infused blood
- Delayed transfusion reaction
- Rh incompatibility
b) Decreased uptake of bilirubin by the liver:
- Certain drugs as listed below
- Congestive heart failure
- Dubin-Johnson syndrome (preconjugation transport failure)
- Gilbert's syndrome
- Portosystemic shunts
c) Bilirubin conjugation failure:
- Breast milk jaundice
- Crigler Najjar syndromes type I and II
- Gilbert's syndrome
- Liver disease:
- Chronic hepatitis
- Cirrhosis
- Wilson's disease
- Maternal serum jaundice
- Neonatal physiological jaundice
- Thyroid disturbances
II. Conjugated hyperbilirubinemia is seen in the following conditions:
a) Hepatocellular dysfunction
- Infection
- Cytomegalovirus (CMV) hepatitis
- Ebstein-Barr virus hepatitis
- Infectious mononucleosis
- Sepsis
- Viral hepatitis
- Inflammation
- Alcoholic hepatitis
- Autoimmune hepatitis
- Drug toxicity as listed below
- Hemochromatosis
- Toxic liver injury
- Wilson's disease
- Metabolic disorders
- Acute fatty liver of pregnancy
- Inborn errors of metabolism
- -1 antitrypsin deficiency
- Benign recurrent cholestasis
- Dubin-Johnson syndrome
- Rotor syndrome
- Other conditions
- Ischemia ("shock liver")
- Preeclampsia
- Reye syndrome
- Total parenteral nutrition
b) Impairment of biliary flow into the intestine
- Diffuse infiltrative diseases
- Amyloidosis
- Disseminated mycobacterial infections
- Extensive malignancy
- Lymphoma
- Sarcoidosis
- Wegener granulomatosis
- Impaired biliary secretion of bilirubin
- Cholangitis
- Cholestatic drugs as listed below
- Intrahepatic biliary ducts or portal tracts damaged
- Arteriohepatic dysplasia
- Benign recurrent intrahepatic cirrhosis
- Byler disease
- Genetic and metabolic disorders
- -1 antitrypsin deficiency
- Cholesterol ester storage disease
- Cystic fibrosis
- Down's Syndrome
- Familial hepatosteatosis
- Fructosemia
- Galactosemia
- Gaucher's disease
- Glycogen Storage Disease Type IV
- Lucey-Driscol syndrome (transient familial neonatal hyperbilirubinemia)
- Neonatal hypopituitarism
- Niemann-Pick disease
- Trisomy 18
- Tyrosinemia
- Wolman's disease
- Zellweger cerebrohepatorenal syndrome
- Graft-versus-host reaction
- Hereditary cholestasis with lymphedema
- Infections
- Bacterial sepsis
- CMV
- Coxsackie virus
- Echovirus
- Hepatitis B
- Herpes
- Rubella
- Syphilis
- Toxoplasmosis
- Varicella
- Paucity of intrahepatic biliary ducts
- Primary biliary cirrhosis
- Sclerosing cholangitis
- Veno-occlusive disease
- Larger bile ducts damaged or obstructed
- Acute pancreatitis
- AIDS cholangiopathy
- Choledochal cyst
- Choledocholithiasis
- Developmental anomalies of the bile ducts
- Biliary atresia
- Extrinsic compression of the bile ducts
- Hepatic arterial chemotherapy
- Neonatal hepatitis
- Post surgical trauma and strictures
- Sclerosing cholangitis
- Tumors
III. Drugs that cause hyperbilirubinemia include:
a) Drugs that cause cholestasis:
- Amitriptyline
- Anabolic steroids/Androgens
- Benzodiazepines
- Chlorothiazide
- Chlorpromazine
- Chlorpropamide
- Dapsone
- Erythromycin
- Estrogens
- Ethionamide
- Gold salts
- Imipramine
- Mercaptopurine
- Nitrofurans
- Oral contraceptives
- Penicillins
- Phenothiazines
- Progesterone
- Propoxyphene
- Sulfonamides
- Tamoxifen
- Tolbutamide
b) Drugs that cause hemolysis:
- Amphotericin B
- Carbamazepine
- Carbutamide
- Cephaloridine
- Cephalothin
- Chlorpromazine
- Chlorpropamide
- Dinitrophenol
- Ibuprofen
- Insulin
- Isoniazid
- Levodopa
- Mefenamic acid
- Melphalan
- Methotrexate
- Methyldopa
- Penicillins
- Phenacetin
- Procainamide
- Quinidine
- Quinine
- Rifampin
- Stibophen
- Sulfonamides
- Tolbutamide
c) Drugs that cause hepatocellular damage (hepatotoxic drugs):
- Acetaminophen
- Acetylsalicylic acid (Aspirin)
- Allopurinol
- Amiodarone
- Anabolic steroids
- Anticonvulsants
- Asparaginase
- Azithromycin
- Bromocriptine
- Bunamiodyl
- Captopril
- Cephalosporins
- Chloramphenicol
- Clindamycin
- Clofibrate
- Danazol
- Enflurane
- Ethambutol
- Ethinyl estradiol
- Ethionamide
- Fenofibrate
- Flavaspidic acid
- Fluconazole
- Fluoroquinolones
- Foscarnet
- Gentamicin
- Indomethacin
- Interferon
- Interleukin-2
- Levamisole
- Levodopa
- Lincomycin
- Low molecular weight heparin
- Methyldopa
- Monoamine oxidase inhibitors
- Naproxen
- Nifedipine
- Nitrofurans
- Oral contraceptives
- Probenecid
- Procainamide
- Quinine
- Ranitidine
- Retinal
- Rifamycin
- Ritodrine
- Sulfonylureas
- Tetracyclines
- Tobramycin
- Verapamil
A low result is typically of no clinical significance.
Drugs, which decrease the serum bilirubin, includ
- Amikacin
- Anticonvulsants
- Aspirin
- Barbiturates
- Carbamazepine
- Cyclosporine
- Hydroxyurea
- Isotretinoin
- Penicillins
- Pindolol
- Prednisone
- Sulfisoxazole
- Theophylline
- Thioridazine
- Ursodiol
- Valproic acid
- British Columbia Ministry of Health. BCHealthGuide. Bilirubin. [Homepage on the Internet] ©1995-2006. Last updated September 3, 2004. Last accessed on October 18, 2006. Available at URL: http://www.bchealthguide.org/kbase/topic/medtest/hw3474/descrip.htm
- Kaplan M et al. Understanding severe hyperbilirubinemia and preventing kernicterus: adjuncts in the interpretation of neonatal serum bilirubin. Clin Chim Acta. 2005 Jun;356(1-2):9-21. Epub 2005 Mar 19
- Lab Tests Online®. Bilirubin The Test. [Homepage on the Internet] ©2001-2006. Last reviewed December 17, 2005. Last accessed on October 18, 2006. Available at URL: http://www.labtestsonline.org/understanding/analytes/bilirubin/test.html
- Melton K, Akinbi HT. Neonatal jaundice: strategies to reduce bilirubin-induced complications. Postgrad Med 1999;106(6):167-78
- Olin JL et al.Amphotericin B-associated hyperbilirubinemia: case report and review of the literature. Pharmacotherapy. 2006 Jul;26(7):1011-7.
- Weinstein A et al. Acute graft-versus-host disease in pancreas transplantation: a comparison of two case presentations and a review of the literature. Transplantation. 2006 Jul 15;82(1):127-31.