Blood Coagulation

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Blood Coagulation

Definition

Blood coagulation is the process that causes blood to clot and helps prevent excessive blood loss when a vein or artery is pierced or broken.

Description

Blood coagulation is the body's natural way of preventing its blood supply from being lost through a cut, puncture, or other trauma to blood vessels. All of the components necessary for coagulation are found in the blood. The coagulation process involves a series of proteins, protein cofactors, and enzymes that interact on membrane surfaces. It is normally activated by damaged tissue.

Function

Normal blood coagulation is a complex process that involves 20 to 30 components, called blood coagulation factors, and a series of complex chemical reactions. When a blood vessel is injured, platelets in the area of the damage clump together and stick to the edges of the cut to begin the coagulation process. Platelets are fragments of cells containing clotting factors. These clotting factors combine with a protein called prothrombin in a reaction that converts prothrombin to thrombin. Thrombin then converts fibrinogen (a protein present in plasma) into long, sticky threads of another protein called fibrin. The fibrin forms a mesh-like net over the opening and traps red blood cells as they try to leak out of the cut. As the clot hardens, it forms a protective seal over the cut.

The platelets also release messengers into the blood that perform additional functions including: constriction of the damaged blood vessels to reduce bleeding, attracting more platelets to the injury site to enlarge the clot, and activating other clotting factors, such as fibrinogen.

Role in human health

The ability of the blood to form a self-sealing clot when a blood vessel is injured is crucial. Without coagulation, a cut or puncture wound, no matter how minor, would continue to bleed and quickly lead to death. A deficiency in any of the protein coagulation factors can result in hemorrhages following injury. In some coagulation disorders, such as hemophilia, the deficiency is due to an inherited defect. In others, the deficiency is due to an acquired condition, such as vitamin K deficiency.

Common diseases and disorders

Hemophilia is an inherited coagulation disorder characterized by the blood's inability to clot. Both types of the disorder, hemophilia A and hemophilia B, are caused by an inherited sex-linked recessive trait, with the defective gene located on the X chromosome. This means only males are affected with the disorder but females can carry the abnormal gene and pass it on to their children.

About 80% of hemophiliacs have type A, which is the result of a deficiency of clotting factor VIII. Symptoms can vary and include bruising, spontaneous bleeding, bleeding into joints, hemorrhaging in the gastrointestinal and urinary tracts, and most notably, prolonged bleeding even from the most minor of cuts.

Prevention of injury is paramount for people with the disorder. When bleeding occurs, the standard treatment is infusion of blood plasma with concentrations of clotting factor VIII. This clotting factor has been cloned through genetic engineering, eliminating the possibility that the blood may contain viruses such as hepatitis and human immunodeficiency virus (HIV). Hemophilia A occurs in about one out of 10,000 males.

Hemophilia B (also called Christmas disease) is a result of a deficiency of clotting factor IX. Symptoms are generally the same as for type A. Treatment is usually infusion of blood plasma with clotting factor IX. The condition occurs in one out of about 70,000 males.

The most common coagulation disorder is thrombosis, which is a blood clot that blocks otherwise normal blood vessels. This is most disastrous when the clot blocks a blood vessel leading to the heart (causing a heart attack), brain (causing a stroke), a limb, or other organ.

Thrombocytopenia is a blood disease characterized by an abnormally low number of platelets in the bloodstream. The normal amount of platelets is usually between 150,000 and 450,000 cells per micro-liter of blood. When this number drops below 150,000, the patient is said to be thrombocytopenic. This blood disorder is one of the most common causes of hemorrhaging.

Treatment and management

Individuals at high risk for developing clots or those who have had them previously can prevent further clots by taking anticoagulant drugs, such as sodium warfarin and heparin. Anticoagulant drugs help prevent the formation of harmful clots in the blood vessels by reducing the blood's ability to clump together. Although these drugs are sometimes called blood thinners, they do not actually thin the blood. Furthermore, this type of medicine will not dissolve clots that have already formed, although the drug may prevent an existing clot from worsening. Because these drugs affect the blood's ability to clot, they can increase the risk of severe bleeding and heavy blood loss. Anticoagulant drugs must be used exactly as directed and a physician should be consulted regularly while taking the medicine. In 2002, sales of heparin were $2.7 billion worldwide.

The first new anticoagulant drug in more than 60 years failed to receive approval by the U.S. Food and Drug Administration (FDA) in 2004 due to concerns that it may cause liver damage. Ximelagatran (Exacta), a direct thrombin inhibitor, was approved by the European Union's regulatory group in May 2004 but had a major setback in the United States when the FDA Cardiovascular and Renal Drugs Advisory Committee convened in September 2004. The advisory committee concluded that the benefits of ximelagatran therapy for any of the uses under consideration did not outweigh the risks, particularly of liver failure.

Medications called fibrinolytic agents are sometimes used to dissolve clots and include streptokinase, urokinase, and tissue plasminogen activator. These are most commonly used for thrombosis.

KEY TERMS

Coagulation— The process of becoming gel-like or solid.

Enzymes— Numerous complex proteins produced by cells in the body and catalyze specific biochemical reactions at body temperatures.

Hemorrhaging— Heavy or uncontrollable bleeding.

Protein cofactor— A substance that acts in conjunction with protein to bring about certain effects.

X chromosome— A sex chromosome that usually occurs in pairs in females and single in male cells.

Resources

BOOKS

Kroll, Michael, et al. Manual of Coagulation Disorders Oxford, United Kingdom: Blackwell Publishing, 2001.

O' Shaughnessy, Denise, et al. Practical Hemostasis and Thrombosis Oxford, United Kingdom: Blackwell Publishing, 2005.

Owen, Charles A. A History of Blood Coagulation Rochester, MN: Mayo Clinic, 2001.

PERIODICALS

NewsRX. "High Levels of Anxiety May Affect Coagulation of Blood." Blood Weekly (Dec. 16, 2004): 129.

Financial Times Information Ltd. "Biotie Therapies Signs Research, Development, and Collaboration Agreement With Aventis to Develop New Heparin-Like Drug for Blood Coagulation Disorders." Europe Intelligence Wire (May 9, 2004): N/A.

Hitchens, Kathy. "Helping Hemophiliacs: The New Therapies Are Safer, Simpler, and Cover Treatment-on-Demand to Prophylaxis." Drug Topics (March 22, 2004): HSE-17.

Magill-Lewis, Jillene. "What is Optimal INR for Preventing Venous Thrombosis?" Drug Topics (Feb. 23, 2004): 39.