Coagulation is the process of blood clot formation, known as a thrombus. The coagulation cascade is the process whereby activation of numerous protein factors in a series come together to create a protective clot. A platelet plug, made up of tiny fragments of precursor cells found in blood, forms first and is reinforced by this protein-based network; together, they create a clot. The body has several regulatory mechanisms to break down clots after they are formed, since normal healing involves both the creation and breakdown of clots. Abnormal clotting occurs when an imbalance develops in this system, which may occur in a variety of genetic or acquired conditions.
Types and Prevalence
Medical conditions that increase the likelihood of blood clots forming carry significant consequences, including the potential for deep vein thrombosis -- a clot in the lower extremities or other sites that can break free and lead to pulmonary embolism -- a clot in the lungs, stroke or death. These clotting disorders can be separated into two groups: inherited or acquired. Inherited clotting disorders affect about 10 percent of the population. Acquired conditions vary in prevalence. A November 2009 study published in the "Journal of Thrombosis and Thrombolysis" found that the incidence of venous thromboembolism -- clot formation in a vein that can travel to other sites -- was higher with increasing age, in women and in those with multiple acquired risk factors such as recent hospitalization, surgery or malignancy.
Genetic Clotting Disorders
Inherited clotting disorders are usually caused by genetic variations in the clotting factors, which can alter their function and lead to changes in either clot formation or breakdown. These can be organized into three general groups, depending on how the factors are affected. Group 1 represents a deficiency of clot inhibitors, meaning less ability to turn off clot formation. Affected factors include antithrombin III, plasminogen, and proteins C and S. The second group includes conditions with an increase in coagulation factors and greater potential for new thrombus formation, such as factor V Leiden, prothrombin deficiency or sickle cell disease. The pathophysiology is unclear for the third group, which includes elevated levels of homocysteine and clotting factors VII, IX and XI.
Acquired Clotting Disorders
Lifestyle, medications and other non-genetic factors, including underlying medical conditions, increase the risk for thrombosis. When blood flow is reduced in the lower extremities for prolonged periods, thrombosis risk increases, as seen in cases of immobility or air travel. Hormonal changes, such as those experienced during pregnancy, from taking oral birth control and while undergoing hormone therapy, can increase the risk of clots as there is a decrease in clot inhibitors and an increase in fibrinogen, the major protein used in forming clots. Smoking increases select clotting factors and fibrinogen levels as well. Cancer increases the risk for thrombosis by creating and releasing certain proteins that can trigger clot formation. Obesity, chemotherapy, previous thrombotic incidents and certain infectious diseases are other risks for acquired clotting abnormalities.
Precautions and Complications
Inherited clotting conditions often go unrecognized, but can make a person more susceptible to other acquired risk factors for clotting. A history of abnormal clotting in other family members, a blood clot at a young age, recurring clots or cases without an obvious cause may indicate the presence of hypercoagulability -- an increased tendency to clot. It is important to talk with your health care provider about your risk factors. If you experience unexplained leg swelling or pain, difficulty breathing or sudden chest pain, seek urgent care as these may be signs of thromboembolism.
- Medical Physiology Second Edition (2003); Rodney A. Rhoades, George A Tanner
- Epocrates: Hypercoagulable State
- Annals of Internal Medicine: Congenital Thrombophilic States Associated with Venous Thrombosis: A Qualitative Overview and Proposed Classification System
- Blood Transfusion: Risk Factors for Venous and Arterial Thrombosis
- Journal of the American Society of Hematology: Advances in Understanding Pathogenic Mechanisms of Thrombophilic Disorders
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- Journal of Thrombosis and Thrombolysis: Incidence rates, clinical profile, and outcomes of patients with venous thromboembolism. The Worcester VTE study