Thrombophilia is a disorder in which the blood clots easily or excessively.

• Inherited and acquired disorders can increase blood clotting.
• Clots cause legs or arms to swell.
• Blood levels of proteins that control clotting are measured.
• People may need anticoagulants.

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.

Causes

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); a specific mutation in the prothrombin gene (prothrombin 20210 mutation); and a deficiency of protein C, protein S, or antithrombin all cause an increase in the production of fibrin, an important protein involved in clot formation. Hyperhomocysteinemia, an increase in the amount of homocysteine (a type of amino acid) in the blood, may increase the risk of clotting in veins and arteries.

Other disorders that cause thrombophilia are acquired after birth. These disorders include disseminated intravascular coagulation (often associated with cancer), and antiphospholipid antibody (anticardiolipin) syndrome (including the presence of the lupus "anticoagulant"), which increase the risk of clotting because of overactivation of blood clotting factors.

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 include 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.

Symptoms and Complications

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. Many people with inherited disorders develop a deep vein clot (deep vein thrombosis) in the legs, 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, causing pain and redness (superficial thrombophlebitis). Less commonly, clots may form in arm veins, abdominal veins, and veins inside the skull. Hyperhomocysteinemia and the antiphospholipid syndrome may result in venous or arterial clots. When clots obstruct blood flow in arteries, tissues lose their blood supply and may be damaged or destroyed.

Diagnosis and Treatment

A person who has had at least two separate instances of a blood clot without an apparent predisposing factor may have an inherited thrombophilia disorder. 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. These tests are usually more accurate when performed after a blood clot has been treated.

The inherited disorders that cause thrombophilia are incurable. People who have had two or more clots are especially likely to be advised to take the anticoagulant warfarin for the rest of their lives. When a person has had only one clot, warfarin or heparin to prevent future clots may be used only when the person is at higher risk for clot formation, including during a period of prolonged bed rest.

People with hyperhomocysteinemia may be advised to take vitamin supplements with folate ( folic acid), vitamin B₆ (pyridoxine), and vitamin B₁₂ (cobalamin), which can reduce homocysteine levels. However, it is unclear whether these supplements also reduce clot formation.

Last full review/revision May 2006 by Joel L. Moake, MD