Molecular Properties

AT is the main physiologic inhibitor of thrombin (activated factor XII, denoted conventionally as factor XIIa).1

AT forms an irreversible covalent bond between its arginine reactive site and the active serine site of thrombin. The result is an inactive 1:1 stoichiometric complex between the 2 molecules.2-4

When heparin binds with AT, a conformational change occurs to the AT molecule, exposing the reactive site and accelerating AT-thrombin complex formation approximately 1000-fold.2,3

Antithrombin Facts

Synonyms Antithrombin III heparin cofactor2,5,6
Plasma concentration 12.5 mg/dL4,7
Functional type Serpin2
Inhibits Thrombin, factors Xa, IXa, XIa, XIIa, kallikrein, and plasmin2
Significance One of the most important inhibitors of coagulation8

References:

  1. Escobar CE, Harmening DM, Joiner Maier DM, Simmons VL, Smith-Moore KM, Wyrick-Glatzel J. Introduction to hemostasis. In: Harmening DM, ed. Clinical Hematology and Fundamentals of Hemostasis. 4th ed. Philadelphia, PA: FA Davis Company; 2002:441-470.
  2. Kottke-Marchant K, Duncan A. Antithrombin deficiency: issues in laboratory diagnosis. Arch Pathol Lab Med. 2002;126(11):1326-1336.
  3. Rosenberg RD, Damus PS. The purification and mechanism of action of human antithrombin-heparin cofactor. J Biol Chem. 1973;248(18):6490-6505.
  4. Thrombate lll [prescribing information]. Research Triangle Park, NC:Talecris Biotherapeutics, Inc.;2009.
  5. Franchini M, Veneri D, Salvagno GL, Manzato F, Lippi G. Inherited thrombophilia. Crit Rev Clin Lab Sci. 2006;43(3):249-290.
  6. Collen D, Schetz J, de Cock F, Holmer E, Verstraete M. Metabolism of antithrombin III (heparin cofactor) in man: effects of venous thrombosis and of heparin administration. Eur J Clin Invest. 1977;7(1):27-35.
  7. Murano G, Williams L, Miller-Andersson M, Aronson DL, King C. Some properties of antithrombin-III and its concentration in human plasma. Thromb Res. 1980;18(1-2):259-262.
  8. Perry DJ. Antithrombin and its inherited deficiencies. Blood Rev. 1994;8(1):37-55.

Important Safety Information

Thrombate III 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 with Thrombate III, the most common side effects were dizziness, chest tightness, nausea, and foul taste in the mouth.

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. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent that can cause disease. There is also the possibility that unknown infectious agents may be present in such products.

Individuals who receive infusions of blood or blood plasma may develop signs and/or symptoms of some viral infections, particularly hepatitis C.

Please speak to your doctor and refer to Thrombate III Prescribing Information for full details.

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