Genetic Predisposition Testing for Venous Thrombo-Embolism

Deep vein thrombosis (DVT) and pulmonary embolism (PE) together comprises VTE. When the clot is in the deep veins such as legs, it is called DVT; while when the clot reaches the lungs, it is called PE. VTE often goes unnoticed. DVT is accompanied by PE, which is a life-threatening condition.

Virchow triad

A combination of factors that cause VTE is often called Virchow triad, named after Rudolf Virchow who first described it. Hypercoagulability (abnormal blood clotting pattern), statis venous (reduction in speed of blood flow) and alteration of blood vessel comprise Virchow triad.

Risk Factors for the development of VTE

The risk factors can be classified as acquired and hereditary.

               Acquired risk factors

1. Diseases that increase chances of development of VTE-Cancer and Atherosclerosis: In 1 of 7 patients who die from cancer, PE was identified as a cause. Immobilization, chemotherapy and surgery including incorporation of central venous catheters enhance the risk of development of VTE in patients with cancer. Atherosclerosis may induce development of VTE, thus corroborating that there is a link between atherosclerosis and VTE
2. Among woman, pregnancy and use of contraceptives are believed to increase the risk of development of VTE. 1 of 100,000 maternal deaths is attributed to PE, while women who take contraceptives or hormonal replacement therapy have 2 to 4 fold increase in chances of development of VTE.
3. Age: Though the chances of development of VTE increases with advanced age, it is not limited to old age. In fact it can affect people of all age groups.
4. Economy class syndrome: There have been cases where long distance air travel leads to the development of VTE, however in such cases patients are already in high risk groups with predisposing factors.
5. D-Dimer: Increased levels of D-dimer poses a higher risk of development of VTE compared to those with lower levels of D-dimer.

               Genetic predisposition

• Deficiency of Protein C, Protein S and anti-thrombin: Protein C, Protein S and anti-thrombin are important for the clotting of blood and deficiency of these can lead to thrombosis. In persons with heterozygotic genotype, the tendency of development of thrombosis is believed to increase by 10 times, while homozygotic children do not survive owing to thrombotic deficiency shortly after birth.
• Effecting around 20% of patients with VTE is a genetic prothrombotic deficiency factor called Factor V Leiden. Among heterozygotes and homozygotes, the chances of development of VTE increases by 3-8 fold and 50-80 fold respectively.
• Prothrombin 20210A mutation is common but restricted to Caucasians and leads to the increased levels of prothrombin. Around 6% of all cases of VTE report this cause.
• Being “O”: In VTE, blood group O reduces the risk of VTE by 2-4 fold compared to blood groups A, B and AB.

Summing up

To conclude, venous thromboembolism is a multi-causal disease caused by the combination of acquired and genetic factors.