Antithrombin deficiency, congenital

Definition

Hypercoagulation disorders (or hypercoagulable states or disorders) have the opposite effect of the more common coagulation disorders. In hypercoagulation, there is an increased tendency for clotting of the blood, which may put a patient at risk for obstruction of veins and arteries (phlebitis or pulmonary embolism).

Description

In normal hemostasis, or the stoppage of bleeding, clots form at the site of the blood vessel's injury. The difference between that sort of clotting and the clotting present in hypercoagulation is that these clots develop in circulating blood.

This disorder can cause clots throughout the body's blood vessels, sometimes creating a condition known as thrombosis. Thrombosis can lead to infarction, or death of tissue, as a result of blocked blood supply to the tissue. However, hypercoagulability does not always lead to thrombosis. In pregnancy, and other hypercoagulable states, the incidence of thrombosis is higher than that of the general population, but is still under 10%. However, in association with certain genetic disorders, hypercoagulation disorders may be more likely to lead to thrombosis. Hypercoagulation disorders may also be known as hyperhomocystinemia, antithrombin III deficiency, factor V leyden, and protein C or protein S deficiency.

Causes & symptoms

Hypercoagulation disorders may be acquired or hereditary. Some of the genetic disorders that lead to hypercoagulation are abnormal clotting factor V, variations in fibrinogen, and deficiencies in proteins C and S. Other body system diseases may also lead to these disorders, including diabetes, sickle cell anemia, congenital heart disease, lupus, thalassemia, polycythemia rubra vera, and others. Antithrombin III deficiency is a hereditary hypercoagulation disorder that affects both sexes. Symptoms include obstruction of a blood vessel by a clot (thromboembolic disease), vein inflammation (phlebitis), and ulcers of the lower parts of the legs. The role of proteins C and S is a complex one. In order for coagulation to occur, platelets (small, round fragments in the blood) help contract blood vessels to lessen blood loss and also to help plug damaged blood vessels. However, the conversion of platelets into actual clots is a complicated web involving proteins that are identified clotting factors. The factors are carried in the plasma, or liquid portion of the blood. Proteins C and S are two of the clotting factors that are present in the plasma to help regulate or activate parts of the clotting process. Protein C is considered an anticoagulant. Mutation defects in the proteins may decrease their concentrations in the blood, and may or may not affect their resulting anticoagulant activity. Factor V is an unstable clotting factor also present in plasma. Abnormal factor V resists the changes that normally occur through the influence of protein C, which can also lead to hypercoagulability. Prothrombin, a glycoprotein which converts to thrombin in the early stage of the clotting process, is affected by the presence of these proteins, as well as other clotting factors.

Diagnosis

The diagnosis of hypercoagulation disorders is completed with a combination of physical examination, medical history, and blood tests. An accurate medical history is important to determine possible symptoms and causes of hypercoagulation disorders. There are a number of blood tests that can determine the presence or absence of proteins, clotting factors, and platelet counts in the blood. Among the tests used to detect hypercoagulation is the Antithrombin III assay. Protein C and Protein S concentrations can be diagnosed with immunoassay or plasma antigen level tests.

Treatment

Coumadin and heparin anticoagulants may be administered to reduce the clotting effects and maintain fluidity in the blood. Heparin is an anticoagulant that prevents thrombus formation and is used primarily for liver and lung clots.

Prognosis

The prognosis for patients with hypercoagulation disorders varies depending on the severity of the clotting and thrombosis. If undetected and untreated, thrombosis could lead to recurrent thrombosis and pulmonary embolism, a potentially fatal problem.

Prevention

Hereditary hypercoagulation disorders may not be prevented. Genetic and blood testing may help determine a person's tendency to develop these disorders.

Key Terms

Antithrombin

Any substance that counters the effect of thrombin, an enzyme that converts fibrinogen into fibrin, leading to blood coagulation.

Congenital

Refers to a condition or disorder present at birth.

Hemostasis

The arrest of bleeding.

Heparin

An anticoagulant, or blood clot "dissolver."

Polycythemia

A condition characterized by an overabundance of red blood cells.

Thalassemia

One of a group of inherited blood disorders characterized by a defect in the metabolism of hemoglobin, or the portion of the red blood cells that transports oxygen throughout the blood stream.

Thrombosis

Formation of a clot in the blood that either blocks, or partially blocks, a blood vessel. The thrombus may lead to infarction, or death of tissue due to a blocked blood supply.

Further Reading

For Your Information

Books

• Conn, Howard F., Clohecy, Robert J. and Conn, Rex B. Current Diagnosis. 9th ed. Philadelphia, PA: W.B. Saunders, 1997.

  Organizations

• National Heart, Lung and Blood Institute. Building 31, Room 4A21, Bethesda, MD 20892. (301) 496-4236. http://www.nhlbi.nih.gov.
• National Hemophilia Foundation. 116 West 32nd St., 11th Floor, New York, NY 10001. 800-42-HANDI. http://wwww.hemophilia.org.

Gale Encyclopedia of Medicine. Gale Research, 1999.