Merck Manual

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Excessive Clotting

(Thrombophilia)

By

Joel L. Moake

, MD, Baylor College of Medicine

Reviewed/Revised Jan 2021 | Modified Sep 2022
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Excessive clotting (thrombophilia) occurs when the blood clots too 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 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:

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 antibody 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 (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 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 Acute Coronary Syndromes (Heart Attack; Myocardial Infarction; Unstable Angina) . 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 Heart Failure (HF) , 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 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.

Complications

Many people with inherited disorders develop a deep vein clot (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 Deep Vein Thrombosis (DVT) ) in a leg, which can result in leg swelling. Formation of a deep leg clot may be followed by 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 . 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 Chronic Venous Insufficiency and Postphlebitic Syndrome ). 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 antibody syndrome may result in clots in arteries or veins.

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, a special nuclear scan Chest Imaging or computed tomography (CT) of the lungs is done.

Treatment of Excessive Clotting

  • Anticoagulants

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.

Drugs Mentioned In This Article

Generic Name Select Brand Names
Coumadin, Jantoven
Hepflush-10 , Hep-Lock, Hep-Lock U/P, Monoject Prefill Advanced Heparin Lock Flush, SASH Normal Saline and Heparin
Pradaxa
Xarelto, Xarelto Granules, Xarelto Starter Pack
Eliquis
Savaysa
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