From the Guidelines
Thrombophilia is primarily inherited through an autosomal dominant pattern, with the most common genetic causes being the Factor V Leiden mutation and the Prothrombin G20210A mutation. The mode of inheritance of thrombophilia is a critical factor in understanding the risk of developing blood clots, particularly in individuals with a family history of the condition. According to the American College of Medical Genetics consensus statement on Factor V Leiden mutation testing 1, the Factor V Leiden mutation is the most common genetic risk factor for venous thrombosis, present in 5% of Caucasian Americans and 20% of idiopathic first venous thrombosis cases.
Key points to consider:
- The Factor V Leiden mutation and Prothrombin G20210A mutation are the most common inherited thrombophilias, typically inherited in an autosomal dominant pattern 1
- Individuals with these mutations have an increased risk of developing blood clots, particularly during high-risk situations like surgery, pregnancy, or prolonged immobility 1
- Genetic testing may be recommended for individuals with a family history of unexplained blood clots, especially at a young age or in unusual locations 1
- Understanding the genetic risk of thrombophilia can help guide preventive measures, such as anticoagulant medications during high-risk periods 1
It is essential to note that while the evidence suggests an autosomal dominant pattern of inheritance for the most common genetic causes of thrombophilia, the condition can also be influenced by acquired or environmental factors, such as pregnancy, oral contraceptive use, or malignancy 1. Therefore, a comprehensive approach to preventing and managing thrombophilia should consider both genetic and environmental risk factors.
From the FDA Drug Label
Hereditary or acquired deficiencies of protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration. The mode of inheritance of thrombophilia is hereditary, as hereditary deficiencies of protein C or its cofactor, protein S, have been associated with tissue necrosis following warfarin administration 2.
From the Research
Mode of Inheritance of Thrombophilia
The mode of inheritance of thrombophilia is complex and involves both genetic and acquired risk factors.
- Thrombophilia may have autosomal dominant, autosomal recessive or X-linked inheritance 3.
- The prothrombin G20210A gene mutation is inherited in an autosomal dominant pattern with variable penetrance 4.
- Factor V Leiden thrombophilia is also inherited in an autosomal dominant pattern, with heterozygous individuals having an increased risk of thrombosis 5, 6.
- Deficiencies in natural anticoagulants, such as antithrombin, protein C, and protein S, can also contribute to thrombophilia and may be inherited in an autosomal recessive pattern 5, 7.
Genetic Risk Factors
Several genetic risk factors have been identified as contributing to thrombophilia, including:
- Factor V Leiden mutation 5, 6, 7
- Prothrombin G20210A mutation 5, 6, 4, 7
- Deficiencies in natural anticoagulants (antithrombin, protein C, and protein S) 5, 7
- Hyperhomocysteinemia 5, 7
- Elevations in clotting factors (factors VIII and XI) 5
Implications of Genetic Risk Factors
Identification of genetic risk factors can help identify patients at high risk of thrombophilia and guide management and treatment decisions 6, 3, 7.