Mechanism of Action (MOA) of Antithrombin (AT)

  • AT, a serine protease inhibitor (or serpin) synthesized in the liver, is the predominant naturally occurring inhibitor of the coagulation cascade1,2
  • AT is responsible for approximately 80% of the endogenous anticoagulation effect against thrombin2,3
  • In the presence of naturally occurring heparin and heparin sulfate, the normal inhibitory activity of antithrombin is sufficient for maintaining balance of the coagulation cascade. When heparin is administered, this anticoagulant effect is accelerated at least a thousand times2,3
  • Activated AT forms irreversible binding complexes with key procoagulant enzymes, most notably Factor Xa and thrombin4
  • Once bound to antithrombin, these factors are rapidly cleared from circulation, preventing the expansion of existing clots and formation of new clots4

THROMBATE III® (antithrombin III [human]) is indicated in patients with hereditary antithrombin deficiency for treatment and prevention of thromboembolism and for prevention of perioperative and peripartum thromboembolism.

Hypersensitivity reactions may occur. Should evidence of an acute hypersensitivity reaction be observed, promptly interrupt the infusion and begin appropriate treatment.

Because THROMBATE III is made from human blood, it may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. There is also the possibility that unknown infectious agents may be present in the product.

Perform coagulation tests to avoid excessive or insufficient anticoagulation and monitor for bleeding or thrombosis. Measure functional plasma AT levels with amidolytic or clotting assays; do not use immunoassays.

In clinical studies, the most common adverse reactions (≥5% of subjects) were dizziness, chest discomfort, nausea, dysgeusia, and pain (cramps).

The anticoagulant effect of heparin is enhanced by concurrent treatment with THROMBATE III in patients with hereditary AT deficiency. Thus, in order to avoid bleeding, the dosage of heparin (or low molecular weight heparin) may need to be reduced during treatment with THROMBATE III.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.


References

  1. Lechner K, Kyrle PA. Antithrombin III concentrates—are they clinically useful? Thromb Haemost . 1995;73(3):340-348.
  2. Rodgers G. Role of antithrombin concentrate in treatment of hereditary antithrombin deficiency. Thromb Haemost . 2009;101:806-812.
  3. Maclean PS, Tait RC. Hereditary and acquired antithrombin deficiency. Epidemiology, Pathogenesis and Treatment Options. Drugs . 2007;67(10):1429-1440.
  4. Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. Haemophilia . 2008;14(6):1229-1239.