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 for the treatment of patients with hereditary antithrombin deficiency in connection with surgical or obstetrical procedures or when they suffer from thromboembolism.

In clinical studies, the most common adverse events were dizziness, chest discomfort, nausea, and dysgeusia.

The anticoagulant effect of heparin is enhanced by concurrent treatment with Thrombate III in patients with hereditary AT-III deficiency. Thus, in order to avoid bleeding, reduced dosage of heparin is recommended during treatment with Thrombate III.

Thrombate III is made from human plasma. Plasma products carry a risk of transmitting infectious agents, such as viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent, despite steps designed to reduce this risk. No cases of transmission of viral disease or CJD have ever been identified for Thrombate III.

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  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.