Inherited and acquired disorders can increase blood clotting.
Clots in larger blood vessels cause legs or arms to swell.
Blood levels of proteins that control clotting are measured.
People may need to be treated with anticoagulants.
(See also How Blood Clots How Blood Clots Hemostasis is the body's way of stopping injured blood vessels from bleeding. Hemostasis includes clotting of the blood. Too little clotting can cause excessive bleeding from minor injury Too... read more .)
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
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 How Blood Clots Hemostasis is the body's way of stopping injured blood vessels from bleeding. Hemostasis includes clotting of the blood. Too little clotting can cause excessive bleeding from minor injury Too... read more )
Elevated clotting factors VIII, IX, and XI
Other disorders that cause thrombophilia are acquired after birth. These disorders include disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation is a condition in which small blood clots develop throughout the bloodstream, blocking small blood vessels. The increased clotting depletes the platelets... read more (often occurring in people with cancer), and antiphospholipid syndrome Antiphospholipid Syndrome Autoimmune disorders, including Graves disease, are more common among women, particularly pregnant women. The abnormal antibodies produced in autoimmune disorders can cross the placenta and... read more (sometimes occurring in people with systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic autoimmune inflammatory connective tissue disorder that can involve joints, kidneys, skin, mucous membranes, and blood vessel walls. Problems in the... read more ), 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 B6 Deficiency Vitamin B6 is in most foods, but people can have vitamin B6 deficiency if they do not absorb it properly. Many foods contain vitamin B6, but extensive processing can remove the vitamin. People... read more , vitamin B12 Vitamin B12 Deficiency Vitamin B12 deficiency can occur in vegans who do not take supplements or as a result of an absorption disorder. Anemia develops, causing paleness, weakness, fatigue, and, if severe, shortness... read more , or folate Folate Deficiency Folate deficiency is common. Because the body stores only a small amount of folate, a diet lacking in folate leads to a deficiency within a few months. Not eating enough raw leafy vegetables... read more ) 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 Acute Coronary Syndromes (Heart Attack; Myocardial Infarction; Unstable Angina) Acute coronary syndromes result from a sudden blockage in a coronary artery. This blockage causes unstable angina or a heart attack (myocardial infarction), depending on the location and amount... read more . Heart failure Heart Failure (HF) Heart failure is a disorder in which the heart is unable to keep up with the demands of the body, leading to reduced blood flow, back-up (congestion) of blood in the veins and lungs, and/or... read more , 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.
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 leg (called deep vein thrombosis Deep Vein Thrombosis (DVT) Deep vein thrombosis is the formation of blood clots (thrombi) in the deep veins, usually in the legs. Blood clots may form in veins if the vein is injured, a disorder causes the blood to clot... read more ) 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 Pulmonary Embolism (PE) Pulmonary embolism is the blocking of an artery of the lung (pulmonary artery) by a collection of solid material brought through the bloodstream (embolus)—usually a blood clot (thrombus) or... read more ), the person has shortness of breath and chest pain (often that is triggered by breathing).
After several deep vein clots have occurred, more serious swelling and skin discoloration may develop (chronic deep vein insufficiency Chronic Venous Insufficiency and Postphlebitic Syndrome Chronic venous insufficiency is damage to leg veins that prevents blood from flowing normally. Postphlebitic syndrome is chronic venous insufficiency that results from a blood clot in the veins... read more ). Sometimes, clots form in superficial leg veins (veins near the surface of the skin), causing pain and redness (superficial thrombophlebitis Superficial Venous Thrombosis Superficial venous thrombosis is inflammation and clotting in a superficial vein, usually in the arms or legs. The skin over the vein becomes red, swollen, and painful. Doctors examine the area... read more ). Less commonly, clots may form in arm veins, abdominal veins, and veins inside the skull. The antiphospholipid syndrome Antiphospholipid Syndrome Autoimmune disorders, including Graves disease, are more common among women, particularly pregnant women. The abnormal antibodies produced in autoimmune disorders can cross the placenta and... read more may result in clots in arteries or veins.
When clots obstruct blood flow in arteries, tissues have a reduced blood supply and may be damaged or destroyed, possibly causing a heart attack Acute Coronary Syndromes (Heart Attack; Myocardial Infarction; Unstable Angina) Acute coronary syndromes result from a sudden blockage in a coronary artery. This blockage causes unstable angina or a heart attack (myocardial infarction), depending on the location and amount... read more or stroke Overview of Stroke A stroke occurs when an artery to the brain becomes blocked or ruptures, resulting in death of an area of brain tissue due to loss of its blood supply (cerebral infarction). Symptoms occur suddenly... read more . 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 Miscarriage A miscarriage is the loss of a fetus before 20 weeks of pregnancy. Miscarriages may occur because of a problem in the fetus (such as a genetic disorder or birth defect) or in the woman (such... read more .
Diagnosis of Excessive Clotting
Blood tests to identify the specific cause of the blood clots
Testing to identify the location of the blood clots
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, computed tomography angiography CT angiography In computed tomography (CT), which used to be called computed axial tomography (CAT), an x-ray source and x-ray detector rotate around a person. In modern scanners, the x-ray detector usually... read more of the lungs or a special nuclear scan Chest Imaging of the lungs is done.
Treatment of Excessive Clotting
People who suddenly develop a blood clot are treated with anticoagulants. Doctors give heparin by vein for a few days and then switch to warfarin by mouth for several months, depending upon the person's existing medical problems. Pregnant women are given only heparin, because warfarin can cause birth defects or severe bleeding in the newborn. People who take warfarin require frequent blood clotting testing and may need their dose adjusted to be sure the level of anticoagulation is right.
Direct oral anticoagulants (DOACs), medications that do not require frequent blood clotting tests, are effective alternatives to oral warfarin. DOACs include dabigatran, rivaroxaban, apixaban, and edoxaban.
People who have had two or more clots are especially likely to be advised to take an anticoagulant such as warfarin or a DOAC for the rest of their lives.
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.
Drugs Mentioned In This Article
|Generic Name||Select Brand Names|
|Hepflush-10 , Hep-Lock, Hep-Lock U/P, Monoject Prefill Advanced Heparin Lock Flush, SASH Normal Saline and Heparin|
|Xarelto, Xarelto Granules, Xarelto Starter Pack|