Blood Clot

A blood clot results from coagulation of the blood (changing from liquid to solid). Blood clots occur at the site of blood vessel damage and involve pooling of the blood (slowing of the blood's motion). There are many situations in which clotting is necessary and appropriate, but there are also times when clots do more harm than good.

The ability of blood to clot is important to control bleeding after an injury. But equally important is the ability to keep blood flowing when a clot is not needed, since clots within blood vessels can prevent oxygen from reaching vital organs.

Abnormal or inappropriate blood clotting cause several important diseases, and several medicines exist to prevent, accelerate, or modify the process of clotting.

Other Names

Blood clot (thrombus). Source: Wikimedia Commons.

• Hemostasis (literally, the process of stopping bleeding)
• Embolus (a type of clot that travels through the vein)
• Thrombus (a clot that stays where it is formed)

Types

Thrombus

A blood clot that forms inside a blood vessel is called a thrombus (plural, thrombi); these usually disrupt blood flow or may stop it entirely. Thrombosis refers to the formation, development, or presence of a thrombus. A deep venous thrombosis, or DVT, is a common type of blood clot that forms in the veins of the leg or arm, and may cause local swelling, or may break off and form an embolus.

Embolus

An embolus (plural, emboli) is any mass that travels from its site of origin to a small blood vessel, where it lodges and obstructs the circulation. Emboli made of blood clots are the most common kind; these are called thromboemboli. Emboli can also be made of air bubbles, tumor fragments, fat, foreign bodies, or amniotic fluid, but these are more rare.

Hemostasis

Hemostasis refers to the stopping of blood flow. Blood clot formation is an important part of hemostasis, but hemostasis also includes the contraction of the blood vessels (vasospasm).

Causes

When a sample of whole blood is allowed to stand, the cells will soon stick together and sink to the bottom of the container, demonstrating that all of the components needed for blood clot formation (coagulation) circulate in whole blood. The ingredients include:

• Soluble proteins (coagulation factors) that travel in the liquid component of whole blood (plasma)
• Platelets
• Red blood cells

Formation

The clotting process begins when the injured blood vessel constricts, so the blood flows more slowly there. The injured blood vessel activates the platelets so they stick to the vessel wall. A substance produced by the vessel wall known as von Willebrand factor helps the platelets stick to the vessel wall. Two of the soluble proteins, collagen and thrombin, help the platelets stick to each other. The platelets change their shape and form a mesh-like plug that traps more platelets and clotting factors, slowing blood loss. Activated platelets also release components which activate additional platelets.

The next stage of hemostasis is divided into the contact activation pathway (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway). The soluble clotting factors that normally circulate in plasma in an inactive state must become active to produce thrombin, which finishes the clotting process. Thrombin converts fibrinogen to strands of fibrin, which fan out from the clump of platelets to trap more platelets and blood cells in the developing clot. The clot soon retracts and solidifies as the fibrin strands shorten and become stronger; enmeshed platelets also contribute to contraction and stabilization of the clot.

Removal

Normal blood clots dissolve during the process of vessel repair in a process termed thrombolysis. This process is carried out by the fibronolytic system, the most important aspect of which is the enzyme fibrinolysin.

Alternatively, blood clots can break free of the surrounding tissue and travel with the flow of blood in a process known as embolization. These thromboemboli frequently lodge downstream in smaller blood vessels, where they occlude blood flow and prevent oxygen from reaching downstream tissues—a process known as infarction. Strokes and heart attacks are sometimes caused by thromboemboli that lodge in arteries supplying the brain and heart muscle, respectively.

A third possible fate of blood clots is organization and recanalization. This slow process involves invasion of the blood clots by surrounding normal cells such as fibroblasts and the establishment of blood flow through the center of the blood clot.

Diseases

Abnormal or inappropriate clot formation is a central feature of many diseases:

• Stroke can result from thromboemboli lodging in arteries that supply the brain.
• Heart attack can result from thrombi or thromboemboli in the coronary arteries, which supply blood to the heart muscle.
• Pulmonary embolism is a blood clot in the large arteries between the heart and lungs.
• Hemophilia is an inherited disease characterized by an increased tendency to bleed. It is caused by abnormalities in one or more coagulation factors.
• Thrombocytopenia, a lack of platelets, results in an increased bleeding tendency.
• Cancer can predispose individuals to either blood clot formation or bleeding tendencies.
• Disseminated intravascular coagulation (DIC) involves widespread thrombus formation with excessive consumption of coagulation factors. Platelets and clotting factors are depleted, resulting in a bleeding tendency. DIC tends to occur alongside severe infections, acute leukemia, envenomations (for example, from bees orsnakes), or trauma. Donated plasma is used to restore the level of clotting factors in the blood.

Tests

Several tests may be used to make sure that the blood clotting system is normal. In general, the tests are designed to activate blood coagulation at a particular step, and the time taken to form a blood clot is measured. The tests include:

Whole blood clotting time

In this test, whole blood is placed in a glass container at room temperature. A clot should form in 5 to 15 minutes and should retract in 30 to 60 minutes. Any abnormality in these times suggests a deficiency in the clotting process or an abnormal increase in fibrinolysis.

Platelet number and function

The number of platelets may be decreased because of accumulation in the liver or kidney (because of disease), destruction from medicine or disease, or a decrease in platelet production (usually because of bone marrow disease or cancer). A low number of platelets can affect clotting, as can abnormal platelet function (commonly caused by medicines like aspirin, blood thinners, antidepressants or antihistamines or diseases like kidney disease or leukemia).

International normalized ratio (INR)

The INR is a test to check the extrinsic pathway of coagulation. Many people are familiar with the test if they are taking the blood thinner warfarin, which requires that they get their INR checked regularly to make sure their blood is not too thinned out. Technically, the INR is the ratio of the patient's prothrombin time divided by the laboratory normal prothrombin time (thrombin time measures the time for conversion of fibrinogen to fibrin).

An increased INR may result from heparin therapy, hemophilia, vitamin K deficiency, severe liver disease, or the anticoagulant medicine coumadin.

Activated partial thromboplastin time (aPTT)

This test evaluates the intrinsic pathway of clotting as well as the common pathway (intrinsic and extrinsic). It is also used to monitor therapy with anticoagulant medicine. The aPTT may be prolonged in hemophilia or with the use of the anticoagulant heparin.

Medications Affecting Blood Clots

Several drugs interfere with normal clot formation:

• Warfarin (marketed as Coumadin) reduces the concentration of prothrombin by inhibiting vitamin K
• Heparin is a naturally-occurring anticoagulant that prevents the formation of clots and extension of existing clots within the blood. It cannot be taken by mouth and must be injected.
• Aspirin is a well-known inhibitor of platelet aggregation.
• Clopidogrel (marketed as Plavix) is a potent inhibitor of platelet aggregation.
• Streptokinase and tissue plasminogen activator (tPA) help dissolve clots in situations such as pulmonary embolism or heart attacks. By dissolving clots rapidly, they can restore blood flow to areas that might otherwise die from lack of oxygen.

Recent News

Detroit Tigers pitcher Jason Bonderman made the U.S. news in June of 2008 when he was sidelined with a blood clot in the arm. ^[1]

Research

The Danish pharmaceutical company Novo Nordisk announced on June 11, 2008, that they would suspend a clinical trial of its product, Novo Seven, because fewer people in the study were dying than expected, and the information the trial was collecting was not likely to be helpful. ^[2] Novo Seven ^[3] is currently used for the treatment of hemophilia and is being studied for efficacy in severe bleeding after trauma.

Birth control pills have long been believed to increase the risk of blood clots, especially in women over the age of 35 and smokers. As hormone doses have been lowered in recent years, this risk has decreased. The risk of blood clots with the birth control patch has been deemed significant, enough that a label update was issued by the FDA in early 2008. ^[4] A recent study revealed that the risk of blood clots in oral and transdermal contraception appears to be the same.^[5]

Hormone replacement therapy does not appear to carry an increased risk of blood clots.^[6]

References

1. ↑ MLB.com. Tigers pitcher undergoes medical procedure for blood clot
2. ↑ CNN Money.com. Novo Nordisk discontinues blood clot drug trial.
3. ↑ Novo Nordisk. Norvo Seven
4. ↑ U.S. Food and Drug Administration. Update to Label on Birth Control Patch.
5. ↑ Johnson JV, Lowell J, Badger GJ, Rosing J, Tchaikovski S, Cushman M. Effects of oral and transdermal hormonal contraception on vascular risk markers: a randomized controlled trial. Obstet Gynecol. 2008 Feb;111(2 Pt 1):278-84. Abstract
6. ↑ Salobir BG, Keber I, Vrabic L. A randomized, placebo-controlled trial of the effects of continuous combined hormone replacement therapy on coagulation and fibrinolytic systems in healthy postmenopausal women. Fertil Steril. 2002 Dec;78(6):1178-83. Abstract

External Resources

National Hemophilia Foundation