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BY: Jeffrey Weitz, MD, Special to Everyday Health

Are Blood Clot Risks in Your Genes?

"While diseases have many causes and risk factors, your family history, your genetics, is always an important risk factor to consider — particularly for common diseases such as cancer, cardiovascular disease, and diabetes. Your genes can also pose a potential risk for blood clots in a condition called venous thromboembolism (VTE). VTE includes blood clots in leg veins, which are called deep vein thrombosis (DVT), and in your lungs, pulmonary embolism (PE).

DVT usually occurs in the deep veins of the legs, where the blood clot causes pain and swelling because outflow of blood from the leg is blocked. If that blood clot breaks loose and travels to the lungs, it causes PE and can be fatal. Blood clots in lung arteries interfere with oxygen exchange and cause shortness of breath and chest pain with breathing, which are symptoms of PE.

Although surveys by the International Society on Thrombosis and Haemostasis (ISTH) Steering Committee for World Thrombosis Day indicate that about half of people haven’t heard of VTE, it’s a very common and potentially deadly condition. It causes more deaths each year in the United States and Europe than breast cancer, HIV, and motor vehicle accidents combined.

- Genetic Disorders and Risks for Blood Clots:
The causes of VTE are complex. They involve interplay among your genes, your environment, and other risk factors that can trigger a blood clot. Genetic disorders that increase the risk of blood clotting affect up to 8 percent of the U.S. population, according to the CDC’s VTE data, and fall into two main categories:

Mutations that promote blood clot formation (called gain-of-function mutations)
Mutations that reduce the levels of naturally occurring blood clot inhibitors (called loss-of-function mutations)
Factor V Leiden and prothrombin gene mutations are the most common hereditary disorders that affect blood clotting. Both gain-of-function mutations, they promote blood clot formation. About 5 percent of the U.S. population has Factor V Leiden, a mutation of a clotting protein in the blood called factor V. If you have Factor V Leiden, you are from 3 to 80 times more likely to have a VTE blood clot than others, according to the NIH Genetic and Rare Diseases Information Center.

Loss-of-function disorders include deficiencies of certain natural blood thinners: proteins in the blood that inhibit clotting, called antithrombin, protein C, and protein S. These are less common disorders.

- Environmental and Triggering Risks for Blood Clots:
The majority of patients with the more common disorders (Factor V Leiden and prothrombin gene mutations) don’t get VTE unless the risk is compounded by environmental or triggering risk factors.

Environmental blood clot risk factors, ongoing things you may have some control over, include:

Taking oral contraceptives (birth control pills)
Taking estrogen replacement therapy (such as during menopause)
Having cancer
Triggering risk factors for blood clots include:

Undergoing surgery
Being hospitalized with prolonged immobilization
Everyone — particularly those with a genetic disorder that promotes blood clotting — needs to receive preventive therapy to stop blood clots in situations where they are at risk for VTE, such as after a major surgery or during hospitalization for a medical illness.

- Testing for Genes That Cause Blood Clots:
You only need testing for genetic disorders that promote blood clotting if having that information would change your medical treatment.

For example, most patients who develop VTE after a transient risk factor, such as major surgery, need a three-month course of treatment with anticoagulants (blood thinners). With such treatment, the risk of recurrent VTE is low regardless of whether you have genetic abnormalities. This is because anticoagulant treatment is just as effective in patients with genetic disorders as it is in those without, so there’s no need to test for these disorders.

Patients who develop unprovoked VTE (without obvious risk factors that might provoke clotting) are at a higher risk of recurrence if they stop their anticoagulant therapy compared with those with provoked VTE. Consequently, many such patients are given long-term treatment with blood thinners. In patients with unprovoked VTE, the risk of recurrence is as high in patients with genetic disorders as it is in those without. So generally, there’s no need for testing here either, because the results do not influence the type or duration of therapy.

So when should you consider testing for genetic disorders?

You may need testing if you have a strong family history of unprovoked VTE, particularly if someone in your family had a fatal blood clot in the lungs at a young age. You may also need testing if you develop unprovoked VTE at a young age, especially if it occurs in an unusual site, such as in veins in your brain or abdomen.

- What Can You Do to Prevent VTE?:
The most important things you can do to prevent blood clots are to stay active, maintain a healthy body weight, and refrain from smoking.

You also need to know the risk factors for VTE so that you can advocate for preventive therapy when you’re going to be in high-risk situations, such as after major surgery or during hospitalization.

Finally, know the signs and symptoms of VTE so that you can seek medical attention should these develop.

- Blood Clot Symptoms You Need to Know:

Symptoms and signs of DVT include:

Pain or tenderness in the calf or thigh
Swelling of the leg, foot, or ankle

Symptoms and signs of PE include:

Shortness of breath
Chest pain with breathing
Rapid heart rate
Lightheadedness or passing out

Even if you don’t have any of the VTE risk factors listed above, seek medical attention immediately if you experience any of these symptoms or signs.

While there’s not a fully defined answer regarding the role of genetics for blood clot risk in every situation, knowing your family history and discussing it with your healthcare professional is a smart and proactive way to take control of your health. Visit the World Thrombosis Day Campaign for more information about VTE.

Jeffrey Weitz, MD, is professor of medicine, and biochemistry and biomedical sciences, at McMaster University and executive director of the Thrombosis and Atherosclerosis Research Institute, both in Hamilton, Ontario. Board certified in internal medicine, hematology, and medical oncology, Dr. Weitz focuses his clinical work in the area of thrombosis. He is on the World Thrombosis Day Steering Committee of the International Society on Thrombosis and Haemostasis".

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