(See also How Blood Clots.)
Most disorders that cause thrombophilia increase the risk of blood clot formation in veins. A few increase the risk of clot formation in both arteries and veins.
Some of the disorders that cause thrombophilia are inherited. Many of these result from changes in the amount or function of certain proteins in the blood that control clotting. For example:
Activated protein C resistance (factor V Leiden mutation)
Deficiency of antithrombin
Deficiency of protein C
Deficiency of protein S
Deficiency of protein Z
Prothrombin 20210 mutation (a specific mutation in the prothrombin gene that causes the body to produce excess prothrombin, a protein involved in the blood clotting process)
Other disorders that cause thrombophilia are acquired after birth. These disorders include disseminated intravascular coagulation (often occurring in people with cancer), and antiphospholipid antibody syndrome (including the presence of the lupus "anticoagulant"), which increase the risk of clotting because of overactivation of blood clotting factors. Hyperhomocysteinemia (an abnormal elevation of homocysteine, most often caused by deficiencies of vitamin B6, vitamin B12, or folate) is a possible cause of thrombophilia.
Other factors may increase the risk of clotting along with thrombophilia. Many involve conditions that result in a person's not moving around sufficiently, causing blood to pool in the veins. Examples are paralysis, prolonged sitting (especially in confined spaces as in a car or airplane), prolonged bed rest, recent surgery, and heart attack. Heart failure, a condition in which the blood is not pumped sufficiently through the bloodstream, is a risk factor. Conditions that result in increased pressure on veins, including obesity and pregnancy, also increase risk.
Most of the inherited disorders do not begin to cause an increased risk of clotting until young adulthood, although clots can form at any age.
Symptoms depend on the location of the blood clot. So if the blood clot travels to the lungs (called pulmonary embolism), the person has shortness of breath and chest pain. A blood clot in a leg (called deep vein thrombosis) causes the leg to be warm, red, and swollen.
Many people with inherited disorders develop a deep vein clot (deep vein thrombosis) in a leg, which can result in leg swelling. Formation of a deep leg clot may be followed by pulmonary embolism. After several deep vein clots have occurred, more serious swelling and skin discoloration may develop (chronic deep vein insufficiency). Sometimes, clots form in superficial leg veins (veins near the surface of the skin), causing pain and redness (superficial thrombophlebitis). Less commonly, clots may form in arm veins, abdominal veins, and veins inside the skull. The antiphospholipid antibody syndrome may result in clots in arteries or veins.
Women may have recurrent miscarriages.
A person who has had at least two separate instances of a blood clot without an apparent predisposing factor may have an inherited disorder that causes thrombophilia. An inherited disorder may also be suspected if a person with an initial blood clot has a family history of blood clots. A young healthy person who develops an initial clot for no apparent reason may have an inherited disorder.
Blood tests that measure the amount or activity of different proteins that control clotting are used to identify specific inherited disorders that cause thrombophilia.
Other testing depends on where the blood clot develops. If a clot is suspected in the leg, an ultrasound is done to look for blockage in a leg vein. If a pulmonary embolism is suspected, a special nuclear scan or computed tomography (CT) of the lungs is done.
The inherited disorders that cause thrombophilia are incurable. People who have had two or more clots are especially likely to be advised to take an anticoagulant such as warfarin (given orally for the rest of their lives). People who take warfarin require frequent testing of blood clotting. When a person has had only one clot, warfarin or heparin (given by injection) to prevent future clots may be used if the person is at higher risk for clot formation, including during a period of prolonged bed rest.
Direct oral anticoagulants (DOACs) are newer drugs that do not require frequent testing of blood clotting and are effective alternatives to oral warfarin. DOACs include dabigatran, rivaroxaban, apixaban, and edoxaban.
Hyperhomocysteinemia is treated with supplements of deficient vitamins.
Other treatment depends on the location of the blood clot.