By Umberto Campia, MD, MS
Brigham and Women’s Hospital
The blood clotting system plays a vital role in stopping bleeding in case of open damage to blood vessels. This vital 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, at times clots form when there is no breach of the vessel wall, causing potentially life-threatening conditions such as a deep vein thrombosis and pulmonary embolism (a clot that travels into the veins and then reaches the lung circulation causing a dangerous obstruction to blood flow).
Some individuals have genetic variations in one or more of their clotting factors that may predispose them to the development of 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 5 most common inherited thrombophilias are called Factor V Leiden (V is the Roman numeral for factor number 5), which affects 3-7% of the population, the prothrombin gene mutation G20210A, which affects 3-7% of the population, and 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-folds, but once a patient has had a clot the risk of a second clot in the future is not much higher than that of a patient without thrombophilia who has 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 the common thrombophilias develop symptoms from it.
2) We don’t have a safe and cost-effective long-term method of preventive treatment if an abnormality is found.
In simple words: the preventive treatment would expose a patient to more risk (such as bleeding) than the possible benefit of not developing a clot.
As these conditions are genetic and may affect more than one member of the same family, another frequent question that experts are often asked is: “My sister had a clot and has thrombophilia: should all family members get tested?”
Commonly, as thrombophilias are autosomal-dominant diseases, 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 >7days, delivery) prophylactic treatment may be considered.
Finally, another common concern that the expert is asked to address is: “I have had a clot, should I be tested?”
In general, the evaluation for thrombophilias in all patients with a diagnosis of clots is not recommended. However, testing is considered appropriate 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 present with: age <45 years; recurrent thrombosis; with thrombosis in multiple veins or unusual veins (abdomen, brain)
If you are concerned about your genetic risk for developing a blood clot, the best thing you can do is discuss your concerns with your healthcare provider. Only your healthcare provider can give you the personalized advice and individualized treatment that you may need.