Antithrombin III is Not a Prothrombin Gene Mutation
No, antithrombin III (ATIII) is not a prothrombin gene mutation but rather a distinct anticoagulant protein that functions as a serine protease inhibitor (SERPIN) in the natural anticoagulant system. 1
Understanding Antithrombin III
Antithrombin III is a key component of the body's natural anticoagulant system with the following characteristics:
- ATIII is a serine protease inhibitor (SERPIN) that acts as a pseudosubstrate to irreversibly inhibit thrombin by covalently binding to the thrombin enzymatic active site 1
- It is produced mainly in the liver and the mature molecule consists of 432 amino acids 2
- ATIII inhibits not only thrombin but also factors Xa, IXa, XIa, XIIa, kallikrein, and plasmin 2
- The rate of thrombin inhibition by antithrombin III is markedly increased by glycosaminoglycans such as heparin 1
Distinguishing ATIII from Prothrombin Gene Mutations
Antithrombin III and prothrombin gene mutations are entirely different entities:
- Antithrombin III is encoded by its own distinct gene located on chromosome 1q23-25 3, 4
- The prothrombin gene mutation (most commonly the 20210A variant) affects the 3' untranslated region of the prothrombin gene, resulting in elevated circulating prothrombin levels 1
- While both ATIII deficiency and prothrombin gene mutations can lead to thrombophilia, they represent different pathophysiological mechanisms 5
Clinical Significance of ATIII vs. Prothrombin Gene Mutation
The distinction between these entities has important clinical implications:
- Inherited ATIII deficiency is associated with a high risk of venous thromboembolism and occurs in approximately 5-20% of thrombophilia patients 1
- The prothrombin 20210A variant is present in 1-2% of the general Caucasian population and is found in 6-8% of patients with first-episode venous thromboembolism 1
- Testing for ATIII deficiency is performed through functional or immunological assays, not through genetic testing for prothrombin mutations 2
- When evaluating patients for thrombophilia, testing for both ATIII deficiency and prothrombin gene mutations may be appropriate as part of a comprehensive thrombophilia workup 1
Common Pitfalls in Understanding Thrombophilia
It's important to avoid these common misconceptions:
- Do not confuse the different components of the anticoagulant system (ATIII, protein C, protein S) with mutations in procoagulant factors (Factor V Leiden, prothrombin 20210A) 1
- Remember that thrombophilia often represents an oligogenetic rather than monogenetic clinical phenotype, with multiple genetic and environmental risk factors contributing to clinical manifestations 5
- ATIII deficiency can be either hereditary (due to various mutations in the ATIII gene) or acquired (due to conditions like severe hepatic dysfunction, nephrotic syndrome, or disseminated intravascular coagulation) 2, 6