Genetic Risk Factors for Blood Clots and the Role of Genetic Testing

Updated October 2019

By Umberto Campia, MD, MS
Brigham and Women’s Hospital

The blood clotting system plays a vital role in stopping bleeding. This function is accomplished by the coordinated work of platelets and a set of circulating inactive clotting factors. When the wall of a vessel is damaged, platelets clump together to form a plug and activate the clotting factors to form a mesh that strengthens the plug itself. This system is tightly regulated so that a blood clot (also called a thrombus) forms only when needed. However, sometimes clots form when there is no breach of the vessel wall, causing potentially life-threatening conditions like deep vein thrombosis (DVT) and pulmonary embolism (PE, a clot that travels into the veins and then reaches the lung circulation, obstructing blood flow).

Some individuals have genetic variations in one or more of their clotting factors that may predispose them to developing a clot, usually in a vein. These genetic variations are collectively called “inherited thrombophilias” (from the Greek words for “clot” and “predisposition”). In the general population, about 10% of people have an inherited thrombophilia, a proportion that increased to about 40% among those who have already developed a clot.

The most common inherited thrombophilias are:

Factor V Leiden (V is the Roman numeral for number 5), which affects 3-7% of the population

Prothrombin gene mutation G20210A, which affects 3-7% of the population

Deficiency of protein C, protein S, and antithrombin, each affecting less than 1% of the population

The presence of these genetic mutations increases the risk of a first clot several-fold, but once a patient has had a clot, the risk of a second clot is not much higher than that of a patient without thrombophilia who’s developed a clot.

Most people at this point would be asking the experts: “If these genetic conditions predispose to clots, shouldn’t we all get tested?”

Surprisingly, the answer is “no” for a number of reasons. Screening (testing in the absence of the disease) in the general population is not recommended because:

1) There are few symptomatic people in the general population, and few people with thrombophilias develop symptoms.

2) We don’t have a safe, cost-effective, long-term method for preventive treatment if an abnormality is found. Preventive treatment would also expose a patient to more risk (such as bleeding), likely outweighing the potential benefit of not developing a clot.

Since these conditions are genetic and may affect more than one member of the same family, another frequent question is: “My sister had a clot and has thrombophilia: should all family members get tested?”

Thrombophilias are autosomal-dominant diseases, so 50% of relatives will carry the same abnormal gene. If the family member also has the genetic abnormality but has not developed clot, then the above considerations for the general population also apply. However, in specific high-risk situations (trauma, surgery, immobilization >7 days, labor/delivery) prophylactic treatment may be considered.

Finally, another common concern is: “I’ve had a clot. Should I be tested?”

In general, evaluating for thrombophilia in patients with clots is not recommended. Testng may be considered in specific populations:

1) Patients with a family history of clot in a first-degree relative before age 45

2) Patients without a family history of clot who are younger than age 45, have recurrent thrombosis, or have thrombosis in multiple veins or unusual veins (such as the abdomen or brain).

If you’re worried about your genetic risk for developing a blood clot, discuss your concerns with your healthcare provider. Your healthcare team can give you personalized advice.

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