Antithrombin

Antithrombin is a glycoprotein that is synthesized in the liver and secreted into the plasma, where it has a half-life of 2 to 3 days. Antithrombin is a serine protease inhibitor that inactivates procoagulant enzymes such as thrombin, factor Xa, and factor IXa. Heparin enhances antithrombin’s anticoagulant activity. Antithrombn is the mediator of heparin’s anticoagulant activity. Decreased levels are associated with an increased risk of thrombosis. 

Hereditary antithrombin deficiency is inherited in an autosomal dominant manner and has an incidence of 1 in 2,500 in the general population. Most patients with hereditary antithrombin deficiency are heterozygous and have plasma antithrombin activity levels of 40% to 70% of normal. Homozygous antithrombin deficiency is incompatible with life. The most common clinical manifestations are idiopathic or recurrent deep vein thrombosis of arms and legs, pulmonary embolism, or mesenteric vein thrombosis. The first episode often occurs in adolescence or early adulthood. Thrombosis is often precipitated by pregnancy or surgery. Antithrombin deficiency can sometimes cause arterial thrombosis such as stroke or myocardial infarction. 

Acquired deficiency of antithrombin is much more common than hereditary deficiency and  may be due to:

• Heparin therapy
• Decreased hepatic synthesis (cirrhosis, chronic hepatitis, congestive heart failure, fatty liver of pregnancy, newborn babies).
• Intravascular coagulation (DIC, pulmonary embolism, trauma, deep vein thrombosis).
• Increased renal or intestinal loss (nephrotic syndrome and protein losing enteropathy).

Drugs can also affect antithrombin levels. Decreased levels are associated with heparin therapy, estrogen, and L-asparaginase. Coumadin increases the Antithrombin level.

Measurement of plasma levels of antithrombin are helpful in the investigation of patients with a history of unexplained or recurrent thrombosis, a suspected or established diagnosis of DIC, and apparent resistance to heparin therapy.

Adult reference range is 80-120%.  

Specimen requirement is one light blue top (sodium citrate) tube of blood. The specimen should be delivered to the laboratory within 2 hours. If not possible, it should be centrifuged and the plasma frozen at -20 C.

References

Viazzer H. Hereditary and acquired antithrombin deficiency. Semin Thromb Hemost. 1999;25(3):257-263.

Van Cott EM et al. Recommendations for clinical laboratory testing for antithrombin deficiency; Communication from the SSC of the ISTH. J Thromb Haemost. 2020;18(1):17-22.