Genetic Evaluation of Hereditary Thrombophilia

TromboGene provides efficient and timely medical actions

It is affordable, accurate, fast and informative

Understanding genetics of  hereditary thrombophilia: risk factors and testing

Did you know that…


10% of the world population can have hereditary thrombophilia


Obesity and diabetes are risk factors contributing for thromboembolism.


Smoking is a modifiable risk factor for thromboembolism.


One of the risk factors for fetal loss and recurrent miscarriage is hereditary thrombophilia. 


The use of oral contraceptives is a well established risk factor for venous thrombosis.

Pulmonary embolism is the third cause of death, right after acute myocardial infarction and stroke.

The most common presentations of venous thrombosis are deep vein thrombosis (DVT) of the lower extremity and pulmonary embolism.

What is Hereditary Thrombophilia?



Thrombophilia is defined as a disorder of hemostasis with an increased risk for blood clots. The development of a blood clot is called thrombosis.  In this disease it is verified a tendency for thrombosis in veins or arteries due to abnormalities in blood composition, blood flow, or the vascular wall.

Blood clots may obstruct blood vessels causing stroke, myocardial infarction or venous thromboembolism (VTE).

VTE is the most common vascular disease after acute myocardial infarction and stroke. It is represented by two main clinical events: deep venous thrombosis (DVT) and pulmonary embolism (PE), which often constitute an unique clinical picture in which PE follows DVT.

Previous thrombotic episodes are a major risk factor for recurrent VTE.

When detected early, there are lifestyle changes and therapeutic measures that can be adopted.


An evidence-based genetic test for hereditary thrombophilia

TromboGene evaluates the genetic risk  for cardio and cerebrovascular diseases, venous thromboembolism, including deep venous thrombosis and pulmonary embolism. 

It is recommended for:

For individuals with personal or family history of:

Deep vein thrombosis

Pulmonary thromboembolism

Stroke or myocardium infarction at young ages

Exposed to environmental risk factors

In a context of obstetrics or family planning, for women:

Planning to be pregnant

With recurrent miscarriages

Planning to take contraceptive pill/estrogen use

Benefits of genetic testing for thrombophilia


1.  Carrier testing.
Identifies individuals who are relatives of patients with documented inherited thrombophilia being possible to provide clinical vigilance and take preventive measures.

2. Women at fertile age.
Provide guidance about the use of oral contraceptives.

3. Preventive.
There are lifestyle changes and therapeutic measures that prevent a thromboembolic event.



1. Actionable.
The genetic test supports clinical diagnosis, establishing the cause of hereditary thrombophilia.

2. Preventive.
There are lifestyle changes and preventive therapeutics that prevent recurrent thromboembolic events.

3. Family planning.
Couples with recurrent miscarriages and/or fetal loss and with a genetic alteration can be advised by a medical doctor or a geneticist to undergo anticoagulant therapy in a future pregnancy.


Start improving the diagnosis of hereditary thrombophilia today

(Only for registered medical doctors, register here)

Download TromboGene Requisition Form: PT | EN | IT | ES

Download TromboGene + WRF Requisition Form: PT | EN | IT| ES

Go back to products  |  Download Product Sheet  |  Need further information? Contact us

TromboGene is a diagnostic tool that identifies the genetic cause of thrombophilia.

The Scientific Background 

1. Genetics of Hereditary Thrombophilia

Hereditary thrombophilia predisposes for venous or arterial thrombosis. 

Results from various clinical and genetic studies [1, 2] established that hereditary thrombophilia may be caused by insufficient coagulation inhibition from: 

a)  genetic alterations that result in natural coagulation inhibitors deficiency;

b) genetic alterations that lead to an increased level / function of coagulation factors.

Hereditary thrombophilia include the following abnormalities: Activated protein C resistance (factor V Leiden mutation), prothrombin gene mutation and hyperhomocysteinemia (MTHFR mutations).

Meta-analysis and other studies show that:

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  [19].

Knowledge about inherited and acquired causes of thrombophilic disorders has increased significantly during the past decade, namely gene-gene and gene-environment interactions and their impact on clinical manifestations. Genetic testing in patients and their relatives can contribute to Predictive, Preventive and Personalised Medicine modifying morbidity and mortality.

2. Prevalence of genetic alterations

– The Factor V Leiden (FVL) mutation is the most prevalent thrombotic risk factor in Caucasian populations (3-7% are carriers) but is very rare in African and Asian populations [3,4].

Prothrombin  G20210A mutation has a prevalence of 0.7%-4% in Caucasian populations [5].

 – Mutations that cause deficiencies in anti-coagulant proteins, such as protein S, protein C or SERPINC1 (antithrombin III) are found in less than 1% of the population [5,6].

– Another genetic factor related to thrombosis is the methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T, which is associated with elevated homocysteine levels and hence causing inflammation. This polymorphism presents a high prevalence in Mediterranean population (33- 46%).


During pregnancy, the thrombogenic potential is enhanced from the hypercoagulable state produced by normal pregnancy-associated changes in several coagulation factors, e.g.

– resistance to activated protein C increases in the second and third trimesters;

protein S activity decreases due to reductions in total and free protein S antigen;

– increase of fibrinogen, factors II, VII, VIII, X and plasminogen activator inhibitor type 1 (PAI-1) and PAI-2 levels.

3. TromboGene Gene Panel

TromboGene genetic test evaluates 14 genetic variants in 10 genes associated to the hereditary predisposition for thromboembolic disorders.

10 Genes (14 Genetic variants)


4. How Genetic variants are selected

1. Research

Our research is supported by highly cited papers that have been published in the reference journals in the field.

2. Selection 

All genetic variants have been validated in reference databases (HGMDP, NCBI-OMIM, NCBI- ClinVar, NCBI-Variation Reporter and Ensembl).

3. Validation 

The knowledge in our databases was approved by internationally recognised medical geneticists and cardiologists.

Validation of the clinical use of the genetic test is focused on three main principles:

1. Analytic validity of the test, which refers to the technical accuracy of the test in detecting a mutation that is present or in excluding a mutation that is absent;

2. Clinical validity of the test, which refers to the diagnostic performance of the test (sensitivity, specificity, positive and negative predictive values) in detecting clinical disease; and

3. Clinical utility of the test, i.e., how the results of the diagnostic test will be used to change management of the patient and whether these changes in management lead to clinically important improvements in health outcomes.

5. International Guidelines

Several international study groups recognize the value of TromboGene genetic testing  to determine the aetiology of thromboembolic disease [3,4,7,8].

  • The International Consensus Guidelines
  • The French Consensus Guidelines
  • The National Institute for Health and Clinical Excellence (NICE)

According to JAMA Internal Medicine [9]:

“… all patients with a positive family history of thrombosis should undergo testing for the common genetic disorders.”

According to the Capital Blue Cross Blue Shield Blue Care Network joint medical policies 2014 [10]:

“The analytic validity of genetic testing for inherited thrombophilia is high. Published literature reports that the analytic sensitivity and specificity for Factor V Leiden mutation testing is greater than 99% and for the prothrombin mutation is higher than 98%.”

6. How to read TromboGene reports?

1.1 Genetic Risk Analysis

1.2 Guidelines Recommendations 

2.0 Technical Information 

3.0 Genetic Information 

3.0 Scientific Evidences For Molecular Markers


 HeartGenetics reports follow the recommendations from the European Society of Human Genetics [35].

European Society of Human Genetics.

Contact us here for complete genetic test model report

Start improving hereditary thrombophilia diagnosis today

(Only for registered medical doctors, register here)

Download TromboGene Requisition Form: PT | EN | IT | ES

Download TromboGene + WRF Requisition Form: PT | EN | ITES

Go back to products  |  Download Product Sheet  |  Need further information? Contact us

8. References

[1] J Genet Couns. 2007. 16(3):261-77. Inherited thrombophilia: key points for genetic counseling.

[2] J Thromb Haemost. 2007. 5 Suppl 1:264-9. Past and future of genetic research in thrombosis. 

[3] 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.

[4] 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.

[5] Br J Haematol. 2008. 143(3):321-35. Does thrombophilia testing help in the clinical management of patients?

[6] Hematology Am Soc Hematol Educ Program. 2005. 1-12. Venous thrombosis: the role of genes, environment, and behavior.

[7]  Int Angiol. 2005. 24(1):1-26. Thrombophilia and venous thromboembolism. International consensus statement. Guidelines according to scientific evidence.

[8] J Mal Vasc. 2009. 34(3):156-203. Recommendations on testing for thrombophilia in venous thromboembolic disease: a French consensus guideline.

[9] Arch Intern Med. 2001. 161(20):2433-9. Hypercoagulability syndromes.

[10] Capital Blue Cross Blue Shield Blue Care Network joint medical policies 2014. Genetic Testing for Inherited Thrombophilia (MP-2.253).