What is antithrombin III (ATIII) deficiency?

Updated: Mar 04, 2020
  • Author: James L Harper, MD; Chief Editor: Hassan M Yaish, MD  more...
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Antithrombin III (ATIII) is a nonvitamin K-dependent protease that inhibits coagulation by neutralizing the enzymatic activity of thrombin (factors IIa, IXa, Xa). Antithrombin III activity is markedly potentiated by heparin, the principal mechanism by which both heparin and low–molecular-weight heparin result in anticoagulation. [1, 2, 3]

Congenital antithrombin III deficiency is an autosomal dominant disorder in which an individual inherits one copy of the SERPINC1 (also called AT3) gene on chromosome 1q25.1, which encodes antithrombin III. This condition leads to increased risk of venous and arterial thrombosis, with an onset of clinical manifestations typically appearing in young adulthood. This form is most commonly diagnosed during childhood by screening after an affected family member has been identified or after a child has had a thrombotic event.

Severe congenital antithrombin III deficiency, in which the individual inherits two defective genes, is a rare autosomal recessive condition associated with increased thrombogenesis, typically noted in the neonatal period or early infancy. This condition is rarely compatible with life. Most affected neonates, however, have heterozygous antithrombin III deficiency rather than the homozygous state.

Acquired antithrombin III deficiency is a deficiency of antithrombin primarily due to consumption or decreased production. It is observed in situations in which activation of the coagulation system is abnormal. Common conditions that result in acquired antithrombin III deficiency include disseminated intravascular coagulation (DIC), microangiopathic hemolytic anemias due to endothelial damage (ie, hemolytic-uremic syndrome), veno-occlusive disease (VOD) (in patients undergoing bone marrow transplantation), sepsis, liver disease, and nephrotic syndrome. Oral contraceptive use and even heparin administration have also been associated with antithrombin III deficiency.

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