Factor V Leiden thrombophilia


Factor V Leiden thrombophilia is a common genetic disorder that leads to a predisposition or increased chance to develop blood clots in the veins (venous thrombosis).


The symptoms of factor V Leiden thrombophilia vary. Some affected individuals have no physical problems. Other individuals will have complications including blood clots blocking blood vessels (thromboembolism), deep vein thrombosis, unexplained multiple miscarriages and stillborn infants, gall bladder dysfunction, strokes, and heart attacks. The most common physical sign of factor V Leiden thrombophilia is thromboembolism (a blockage in the veins caused by a free floating clot [embolus]). Venous thromboembolism is most common in the deep veins of the legs (deep venous thrombosis or DVT of the legs). Since non-specific and common factor V Leiden thrombophilia is suspected in individuals who have had multiple blood clots in the veins (venous thrombosis), more than three unexplained miscarriages, or a family history of individuals with multiple blood clots in the blood vessels.


Factor V Leiden thrombophilia is a disorder caused by an inherited change or mutation in the genetic instructions for making a substance called factor V. The factor V change leads to an increased chance to develop blood clots in blood vessels. Blood clots form in two steps. In the first step, the body produces platelets that are "sticky" and can form initial plugs or clots when needed. However, the first platelets only form the first temporary plugs. To form a more lasting plug or clot the platelets release chemicals to attract more platelets and other substances called clotting factors (or clotting proteins). In the second step, the platelets come together with the clotting proteins and form fibers. The fibers weave together and make the clot stronger and longer lasting.


Diagnosis of factor V Leiden thrombophilia can be done through a blood coagulation screening test or DNA analysis of the gene that codes for factor V. The blood coagulation screening test uses the breakdown protein APC in a resistance study to see how quickly the factor V is broken down as compared to other blood clotting factors. An individual with factor V Leiden thrombophilia has factor V that is resistant or much slower to being broken down by the APC protein. At this time there are two types of APC resistance screening tests for factor V Leiden thrombophilia. The preferred test is the "modified second generation" APC resistance study because an extra step in the testing (dilution by plasma without factor V) makes it almost 100% accurate even in pregnant women and patients being treated by medications such as heparin and warfarin. The DNA or molecular analysis examines the F5 gene to learn if the gene is altered or mutated. Prenatal diagnosis is not offered routinely because the disorder is fairly mild and effective treatment is available.


Individuals affected by factor V Leiden thrombophilia have a wide range of symptoms and signs. Some individuals affected by factor V Leiden thrombophilia will never develop physical signs and symptoms of the disorder. Other individuals will be more severely affected. Most affected individuals will not experience their first clotting event until adulthood. However, individuals with homozygous factor V Leiden thrombophilia have a significantly increased risk to have symptoms of the disease at a younger age. Treatment and close management of the disorder can reduce the risk of thromboembolism significantly.


The treatment and management of individuals affected by factor V Leiden thrombophilia is focused on prevention of floating blood clots (thrombosis) and thromboembolism. The management of affected individuals should be overseen by a hematologist who specialized in blood clotting disorders and a general practitioner or internist who can work closely with the hematologist. At different times of life, different specialists may need to be added. For example, when pregnant, a perinatologist or high-risk obstetrician should work with the hematologist during pregnancy. Additionally, individuals who have had a deep vein clot or stroke may need to consult a vascular specialist and/or neurologist. The physicians managing an affected individual's care should discuss with them the timing, risks, and benefits of taking birth control pills and taking "blood thinning" anticoagulant medications like warfarin, aspirin, and heparin. Individuals affected by factor V Leiden thrombophilia should also be examined to make sure they do not have other blood clotting disorders in addition to factor V Leiden thrombophilia.