Synonym

• A-Th3
• AT-III
• Functional Antithrombin III
• Heparin cofactor assay

Tubes

• Light blue top (sodium citrate) tube
• 5 mL of venous blood

Additional information:

• Should be delivered to lab within 30 minutes of drawing (up to 4 hours still acceptable)
• Plasma should be separated and frozen in a plastic vial immediately on arrival to lab
• If the patient is on heparin, the drug should be withdrawn for at least 6 hr before drawing the sample
• Patient factors that can interfere with results include elevated hemoglobin, bilirubin or lipids

Info

• The antithrombin III activity test is performed to evaluate the normal functioning of antithrombin
• Antithrombin prevents and regulates the blood clotting mechanism
• Antithrombin III is a glycoprotein synthesized in the liver, and is a non-vitamin K dependent serine protease inhibitor (serpine) that inhibits the action of thrombin and factors IXa, Xa, XIa, XIIa, plasmin and kallikrein

Clinical

Antithrombin III (AT III) testing is useful to:

• To investigate the tendency for thrombosis
• AT III levels between 50 and 75% indicate moderate risk
• AT III levels <50% indicate significant risk
• As an initial screening test in type 1 and type 2 antithrombin deficiencies
• As an additional test in patients who do not show the expected response to anticoagulant therapy

Additional information:

• AT III testing should usually not be conducted until any existing areas of thrombosis in the body have resolved, and the patient is no longer on anticoagulant therapy
• Hemostatic abnormalities due to AT III deficiency may be associated with unexplained strokes in young patients
• AT III activity is markedly potentiated by heparin

Antithrombin Deficiency Overview:

• Inherited as an autosomal dominant trait
• Type I deficiency occurs due to reduced synthesis of AT III
• Type II deficiency occurs as result of production of an AT III protein with abnormal function
• Clinical features:
• Venous thrombosis, commonly of the lower limbs
• Venous thrombosis at other sites
• Arterial thrombosis, rarely
• Patients with AT III deficiency show some level of resistance to heparin therapy
• Resistance to heparin therapy is not a good indicator of AT III deficiency, as it may also occur in patients not deficient in AT III

Related laboratory tests include:

• Anticardiolipin antibody
• Antinuclear antibody
• Antiphospholipid antibody
• aPTT
• Coagulation factors
• D-Dimer
• Erythroid sedimentation rate
• Factor V Leiden
• Fibrinogen
• Homocysteine
• Lupus anticoagulant
• Protein C & S
• PT
• Rheumatoid factor
• Vitamin K

Nl Result

Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

Functional Assay

Immunologic Assay

High Result

Antithrombin III activity is increased in the following conditions:

• Liver diseases
• Acute hepatitis
• Obstructive jaundice
• Other conditions
• Acute renal failure
• Hyperglobulinemia
• Inflammation
• Menstruation
• Renal transplantation
• Vitamin K deficiency

Drugs that increase AT III activity include:

• Anabolic steroids
• Gemfibrozil
• Warfarin

Low Result

Antithrombin III activity is decreased in the following conditions:

• Liver disorders
• Chronic liver failure
• Cirrhosis
• Liver transplantation
• Partial hepatectomy
• Other conditions
• Acute leukemia
• Carcinoma
• Deep venous thrombosis
• Disseminated intravascular coagulation
• Familial AT III deficiency (Autosomal Dominant)
• Fibrinolytic disorders
• Heparin failure
• Infants < 6 monts have ~50% reduction in AT III activity
• Nephrotic syndrome
• Postsurgical
• Pregnancy induced hypertension
• Pulmonary embolism
• Recurrent miscarriage
• Sepsis (Gram negative)
• Thrombophlebitis
• Trauma (Major)

Drugs that decrease AT III activity include:

• Asparaginase
• Estrogens
• Gestodene
• Heparin (IV for more than 3 days)
• Oral contraceptives

References

• Cansun Demir S et al. The relationship between pregnancy induced hypertension and congenital thrombophilia. Saudi Med J. 2006 Aug;27(8):1161-6.
• Dixit A et al. Roles of protein C, protein S, and antithrombin III in acute leukemia. Am J Hepatol. 2006 Mar;81(3):171-4.
• Kostka B et al. [Antithrombin III activity in the elderly--association with cardiovascular disease risk factors] [Article in Polish] Przegl Lek. 2005;62 Suppl 3:35-8
• LabTestsOnline®. Antithrombin (III).[Homepage on the Internet]© 2001-2006. Last reviewed on October 25, 2004. Last accessed on October 13, 2006. Available at URL: http://www.labtestsonline.org/understanding/analytes/antithrombin/sample.html
• Lauterbach R et al. Plasma antithrombin III and protein C levels in early recognition of late-onset sepsis in newborns. Eur J Pediatr. 2006 Sep;165(9):585-9. Epub 2006 Apr 25.
• Onderoglu L et al.High frequency of thrombophilic disorders in women with recurrent fetal miscarriage. Clin Exp Obstet Gynecol. 2006;33(1):50-4.