Antithrombin

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antithrombin 1

antithrombin 2

antithrombin reactive site loop sequence

Antithrom+heparin

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Throm+anti+hep complex

Antithrombin (AT), also known as antithrombin III (AT III) and previously as antithrombin III-S, is a small protein molecule that plays an important role in helping to regulate blood coagulation. Antithrombin is a serine protease inhibitor (serpin) that inactivates several enzymes of the coagulation system. Its main target is thrombin, but it also inactivates other enzymes such as Factor Xa, Factor IXa, and Factor XIa. The inactivation of these enzymes by antithrombin significantly reduces the clotting ability of the blood, making antithrombin a key component in the natural anticoagulant system.

Function

Antithrombin inhibits thrombin and other clotting factors by binding to them in a 1:1 stoichiometry, which effectively reduces the clotting capability of the blood and prevents the formation of harmful blood clots. This inhibition is greatly enhanced (by up to 1000-fold) in the presence of heparin, a glycosaminoglycan that is often used therapeutically as an anticoagulant. Heparin increases the activity of antithrombin, making the anticoagulant system more effective.

Genetics

The gene for antithrombin is located on the long arm of chromosome 1 (1q23-25). Mutations in this gene can lead to antithrombin deficiency, which is associated with an increased risk of venous thromboembolism (VTE). There are two types of antithrombin deficiency: Type I (quantitative deficiency) and Type II (qualitative deficiency). Type I is characterized by a reduced level of antithrombin in the blood, while Type II is characterized by the presence of a normal or near-normal level of a dysfunctional antithrombin molecule.

Clinical significance

Antithrombin deficiency is a rare but significant risk factor for the development of venous thromboembolism. Individuals with antithrombin deficiency may require anticoagulant therapy, especially during high-risk situations such as surgery, pregnancy, or prolonged immobilization. Additionally, antithrombin concentrates can be used in certain clinical situations to increase antithrombin levels in the blood and reduce the risk of clotting.

Antithrombin therapy

Antithrombin concentrates, derived from human plasma or produced through recombinant technology, are used in the treatment of patients with hereditary or acquired antithrombin deficiency. These concentrates are particularly useful in situations where the risk of thrombosis is increased, such as during surgery or childbirth in individuals with antithrombin deficiency.

History

The discovery of antithrombin dates back to 1905 when it was first described by Morawitz. Its role in coagulation and its interaction with heparin were further elucidated in the following decades, leading to its current understanding as a critical component of the coagulation cascade and its regulation.