Thrombophilia is a hemostasis disorder with an increased risk of blood clots or thrombosis. There is a predisposition for thrombosis in veins or arteries due to abnormalities in blood composition, blood flow, or the vascular wall.
Results from various clinical and genetic studies [1, 2] established that hereditary thrombophilia may be caused by insufficient coagulation inhibition from:
- genetic alterations that result in natural coagulation inhibitors deficiency;
- genetic alterations that lead to an increased level / function of coagulation factors.
10% of the world population can have hereditary thrombophilia.
Pulmonary embolism is the third cause of death.
Hereditary thrombophilia is one of the risk factors for fetal loss and recurrent miscarriage.
The use of oral contraceptives is a well established risk factor for venous thrombosis.
Venous thromboembolism is associated with acute myocardial infarction and stroke.
TromboGene Genetic Test
TromboGene is an evidence-based genetic test for hereditary thrombophilia from HeartGenetics. TromboGene evaluates the genetic risk for cardio and cerebrovascular diseases, venous thromboembolism, including deep venous thrombosis and pulmonary embolism.
The use of genetic testing for hereditary thrombophilia can be considered in several clinical situations, including the following:
- Evaluation of patients that are considered of high risk for thrombosis, e.g. planned major surgery, or estrogen use.
- Assessment of the risk for thrombosis in asymptomatic patients, meaning screening for inherited thrombophilia
- Evaluation of pregnancy with or without history of complications, including recurrent pregnancy loss and recurrent early pregnancy loss
- Evaluation of close relatives of patients with documented inherited thrombophilia, or with a clinical and family history that is consistent with an inherited thrombophilia
- Factor V Leiden (F5) and Prothrombin (F2) mutations are associated with coronary artery disease, stroke, pulmonary embolism, fetal loss and increased risk for thromboembolism in women under hormonal therapy [11-18].
- MTHFR genetic polymorphisms may be a susceptibility factor that increase the predisposition for vascular thrombosis, stroke, coronary heart disease, and peripheral arterial disease [20-24].
- PAI-1 genetic polymorphisms may be associated with an increased risk for deep venous thromboembolism, myocardial infarction, portal vein thrombosis, fetal loss, implantation failure and preeclampsia in the presence of other genetic variants and acquired or modifiable risk factors associated with thrombophilia [25-28].
- Protein C receptor mutations are associated with venous and arterial thromboembolism [14,29-32].
- Protein S mutations are associated with venous and arterial thromboembolism and fetal loss [14,17,32].
- Antithrombin mutations (SERPINC1) are associated with venous thromboembolism and cardiovascular disease [14,32-34].
- Fibrinogen beta chain (FGB) mutation may be a susceptibility factor for stroke, venous thrombosis and coronary artery disease if combined with other risk factors .
TromboGene genetic test evaluates 14 genetic variants in 10 genes.
F2, F5, GP1BA, PROCR, PAI-1, MTHFR, PROS1, SERPINC1, F13A1 and FGB.
NOTE: By request, we can also include in the TromboGene panel the Factor XII genetic variant.
International Medical Guidelines
Several international study groups recognize the value of the genetic test to determine the aetiology of hereditary thrombophilia [3,4,7,8,9,10].
- Guidelines from Scientific Societies and Working Groups for inherited thrombophilia
- The French Consensus Guidelines for venous thromboembolic disease
- The National Institute for Health and Clinical Excellence (NICE) for venous thromboembolic diseases
- Guideline for the evaluation and treatment of hereditary thrombophilia
The TromboGene genetic report includes a section identified as “Guideline Recommendations”. This section presents guidance from the “Anticoagulation Forum”, taking into account:
- previous thrombotic events;
- family history;
- previous fetal loss;
- estrogen use.
 J Genet Couns. 2007. 16(3):261-77. Inherited thrombophilia: key points for genetic counseling.
 J Thromb Haemost. 2007. 5 Suppl 1:264-9. Past and future of genetic research in thrombosis.
 NICE. Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing. Clinical guideline 144. London: National Institute for Health and Clinical Excellence, 2012.
 Thromb Haemost. 2013. 110(4):697-705. Testing for inherited thrombophilia and consequences for antithrombotic prophylaxis in patients with venous thromboembolism and their relatives. A review of the Guidelines from Scientific Societies and Working Groups.
 Br J Haematol. 2008. 143(3):321-35. Does thrombophilia testing help in the clinical management of patients?
 Hematology Am Soc Hematol Educ Program. 2005. 1-12. Venous thrombosis: the role of genes, environment, and behavior.
 Int Angiol. 2005. 24(1):1-26. Thrombophilia and venous thromboembolism. International consensus statement. Guidelines according to scientific evidence.
 J Mal Vasc. 2009. 34(3):156-203. Recommendations on testing for thrombophilia in venous thromboembolic disease: a French consensus guideline.
 Capital Blue Cross Blue Shield Blue Care Network joint medical policies 2014. Genetic Testing for Inherited Thrombophilia (MP-2.253).
 J Thromb Thrombolysis. 2016 Jan;41(1):154-64. doi: 10.1007/s11239-015-1316-1.
Guidance for the evaluation and treatment of hereditary and acquired thrombophilia.