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Antithrombin Deficiency

Antithrombin Deficiency is a topic covered in the 5-Minute Clinical Consult.

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  • Antithrombin is a glycoprotein that inhibits thrombin by forming an irreversible complex.
  • There are two active sites: one that binds to heparin and one that binds to thrombin/target enzyme.
  • Antithrombin can also inhibit factors Xa, IXa, and XIa. This process is catalyzed by the presence of heparin.
  • Patients deficient in antithrombin have an increased incidence of venous thrombosis, including deep vein thrombosis (DVT) of the lower extremity. Arterial thrombosis is much less common in patients deficient in antithrombin.
  • System(s) affected: cardiovascular, nervous, pulmonary, reproductive, hematologic, lymphatic/immunologic
  • Synonym(s): antithrombin III deficiency


  • Predominant age: Mean age of first thrombosis is in 2nd decade, usually after puberty.
  • Predominant sex: male = female
  • No racial or ethnic predisposition

1/20 to 1/200 with thrombophilia (1)

1/2,000 to 1/5,000 of normal individuals (1)

Etiology and Pathophysiology

  • Hereditary deficiency (2)
    • Type I deficiency is characterized by low levels of antigen (decreased synthesis). Plasma levels of antithrombin are often <50%.
    • Type II deficiency is found when the antithrombin molecule is dysfunctional (decreased function).
    • Type II deficiencies are due to mutations in either the active center of antithrombin that binds the target enzyme or the heparin-binding site.
    • No patients homozygous for defects in the active center have been described, suggesting that this is a lethal condition. Patients heterozygous for mutations in the heparin-binding site rarely have thrombotic episodes.
  • Acquired deficiency (2)
    • Many clinical conditions are associated with antithrombin deficiency, such as those listed under “Follow-Up Tests & Special Considerations,” but limited evidence suggests these deficiencies contribute to increased thrombosis.

Autosomal dominant with variable clinical penetrance

Risk Factors

  • Oral contraceptives, pregnancy, surgery, trauma, and the use of hormone replacement therapy (HRT) increase the risk of venous thrombosis in patients with antithrombin deficiency.
  • Patients with antithrombin deficiency and another prothrombotic state, such as factor V Leiden or the prothrombin G20210A mutation, have increased rates of thrombosis.

Pregnancy Considerations
Increased thrombotic risk from 18% to 70% and specific complications may include preeclampsia, eclampsia, placental abruption, HELLP, premature birth, and recurrent pregnancy loss (3).

General Prevention

Patients with antithrombin deficiency without a history of thrombosis do not require prophylactic treatment.

Commonly Associated Conditions

Venous thromboembolism

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Stephens, Mark B., et al., editors. "Antithrombin Deficiency." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688201/all/Antithrombin_Deficiency.
Antithrombin Deficiency. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688201/all/Antithrombin_Deficiency. Accessed April 26, 2019.
Antithrombin Deficiency. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688201/all/Antithrombin_Deficiency
Antithrombin Deficiency [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 26]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688201/all/Antithrombin_Deficiency.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Antithrombin Deficiency ID - 1688201 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688201/all/Antithrombin_Deficiency PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -