Excessive clotting (thrombophilia) occurs when the blood clots too easily or excessively.
Inherited and acquired disorders can increase blood clotting.
Symptoms depend upon which blood vessels clots form in.
Blood levels of proteins that control clotting are measured.
People may need to be treated with anticoagulants.
(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.
Causes of Excessive Clotting
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)
Elevated clotting factors VIII, IX, and XI
Other disorders that cause thrombophilia are acquired after birth. These disorders include disseminated intravascular coagulation (often occurring in people with cancer), and antiphospholipid syndrome (sometimes occurring in people with systemic lupus erythematosus), 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.
Many other factors that increase the risk of clotting 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 in the legs, including obesity and pregnancy, also increase risk. The risk is even greater in people who have thrombophilia and one of these other risk factors.
Symptoms of Excessive Clotting
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. A blood clot in a deep vein in a leg (called deep vein thrombosis) causes leg pain in the calf or thigh as well as warmth, redness, and swelling in the leg. If the blood clot travels to the lungs (called pulmonary embolism), the person has shortness of breath and chest pain (often that is triggered by breathing). Less commonly, clots may form in the deep veins of the arm, abdomen (portal, mesenteric or hepatic vein thrombosis), or brain (cerebral venous sinus thrombosis).
Blood clots can also develop in superficial veins close to the surface of the skin (called superficial thrombophlebitis or superficial vein thrombosis). Typically people develop swelling, pain, redness, and warmth confined to the affected superficial vein under the surface of the skin.
Blood clots in the deep veins of the leg or arm can cause chronic swelling and skin discoloration or ulcers in the affected extremity (called postthrombotic syndrome).
When clots obstruct blood flow in arteries, tissues have a reduced blood supply and may be damaged or destroyed, possibly causing a heart attack or stroke. Clots in leg or arm arteries cause the leg or arm to be cold, painful, and sometimes numb.
Blood clotting disorders can cause women to have recurrent miscarriages, typically in the second or third trimester of pregnancy.
Diagnosis of Excessive Clotting
Blood tests to identify the specific cause of the blood clots
Testing to identify the location of the blood clots
People who develop a blood clot without an obvious cause (such as paralysis, prolonged bed rest, recent surgery) are more likely to have an inherited tendency to blood clotting (thrombophilia), particularly if they are younger than 50 years of age. An inherited disorder may also be suspected if a person with an initial blood clot has a family history of blood clots.
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 a blockage in a leg vein. If a pulmonary embolism is suspected, computed tomography angiography of the lungs or a special nuclear scan of the lungs is done.
Treatment of Excessive Clotting
Anticoagulants
People who suddenly develop a blood clot are treated with anticoagulants. Anticoagulants are medications that stop the formation of blood clots. They include heparin, warfarin, and the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban. People who suddenly develop a blood clot are treated with anticoagulants. Anticoagulants are medications that stop the formation of blood clots. They include heparin, warfarin, and the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban.
People who are hospitalized with a blood clot are usually given low molecular weight heparin (LMWH) or unfractionated heparin (UFH) by vein for several days before they are transitioned to a DOAC or warfarin by mouth. People who do not require hospitalization can be started on some (but not all) DOACs without first receiving heparin or other intravenous anticoagulants. Pregnant women are given only heparin, because warfarin can cause birth defects or severe bleeding in the newborn. Likewise, DOACs are not considered safe for use during pregnancy.
People who take warfarin require frequent blood testing and may need their dose adjusted to be sure the level of anticoagulation is right. DOACs do not require frequent blood clotting tests and are effective alternatives to oral warfarin.
People who have had deep vein clots without a clear cause or recurrent blood clots are often advised to take an anticoagulant such as warfarin or a DOAC for the rest of their lives. Decisions regarding long-term anticoagulation in individual people need to take into account risk of bleeding.
The inherited disorders that cause thrombophilia cannot be cured.
Hyperhomocysteinemia is treated with supplements of deficient vitamins, but there is no clear evidence that treatment reduces the risk of clotting.
Other treatment depends on the location of the blood clot.
