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Published on: September 9, 2012
Inherited antithrombin deficiency: a review
1Department of Internal Medicine, University of Minnesota School of Medicine, Minneapolis, MN, USA.
Insights
Antithrombin (AT) deficiency, a rare inherited condition, increases the risk of venous thromboembolism (VTE). Diagnosis requires functional and antigenic assays after excluding acquired causes, guiding VTE prophylaxis and treatment.
Area of Science:
- Hematology
- Coagulation Science
- Thrombophilia Research
Background:
- Antithrombin (AT) is a critical inhibitor of blood coagulation, primarily inactivating thrombin and factor Xa.
- Inherited AT deficiencies, affecting 1 in 500 to 5000 individuals, are classified as quantitative (Type I) or qualitative (Type II).
- Type II deficiencies include Type IIb (heparin-binding region defect) and Type IIa (thrombin-binding site mutation), with Type IIa being more thrombogenic.
Purpose of the Study:
- To outline the diagnostic approach for antithrombin deficiency in individuals with thrombophilia.
- To discuss the association between AT deficiency and the risk of venous thromboembolism (VTE) and pregnancy loss.
- To present current VTE prophylaxis and treatment guidelines for AT deficiency and address data gaps regarding AT concentrates.
Main Methods:
- Utilizing functional AT activity assays for initial screening in thrombophilic individuals.
- Confirming diagnosis by ruling out acquired causes and repeating AT testing on a separate sample.
- Employing antigenic AT assays to differentiate between Type I and Type II deficiencies, with specialized tests for subclassification.
Main Results:
- AT deficiency is strongly associated with an increased risk of venous thromboembolism (VTE) and pregnancy loss.
- The link between AT deficiency and arterial thrombosis is considered weak.
- Current guidelines for VTE prophylaxis and treatment management exist, but data on AT concentrate usage remains limited.
Conclusions:
- Accurate diagnosis of AT deficiency involves functional and antigenic assays, excluding acquired causes.
- AT deficiency significantly elevates the risk for VTE and adverse pregnancy outcomes.
- Further research is needed to clarify the optimal use of AT concentrates in managing AT deficiency.
Abstract:
Antithrombin (AT) is a potent inactivator of thrombin and factor Xa and the major inhibitor of blood coagulation. Inherited AT deficiencies are uncommon, with prevalences in the general population between 1 in 500 and 1 in 5000. They are either quantitative (type I) or qualitative (type II). Type II is subdivided into the more common, but less thrombogenic, type IIb deficiency caused by a defect in the heparin-binding region of AT and the less common, but more thrombophilic, type IIa variant caused by mutations in the thrombin-binding site. A pleiotropic type IIc deficiency also exists. In the evaluation of a thrombophilic individual, a functional AT assay (AT activity) should be used and the diagnosis of AT deficiency only established after acquired causes have been ruled out and repeat AT testing on an additional sample has been performed. A subsequent antigenic AT assay result leads to differentiation between type I and type II deficiency. Further specialized tests help subclassify the type II deficiencies, but this is typically not carried out for clinical purposes, even though it might be helpful to assess thrombosis risk. AT deficiency is associated with an increased risk for venous thromboembolism (VTE) and pregnancy loss. The association with arterial thrombosis is only weak. VTE prophylaxis and treatment management will be discussed in this article and existing treatment guidelines presented. The lack of data surrounding the use of AT concentrates and the resulting ambiguity as to when to use such concentrates will be discussed.
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