Antithrombin (AT), also known as antithrombin III (AT III), is a protein molecule and thrombin inhibitor found in blood plasma. Thrombin is one of the key parts of the body’s coagulation system, and keeping balance in this system requires that thrombin be inhibited, or inactivated. In addition to working in the coagulation system, antithrombin can act as an anti-inflammatory.
The coagulation system is a complex chain reaction designed to produce clots where and when they are needed. Clotting is the process by which blood flow to an injury, such as a cut, can be stopped so a person doesn’t bleed to death. AT works by inhibiting thrombin, Factor Xa, and Factor IXa, which are clotting enzymes. Factor Xa and Factor IXa contribute to the creation of thrombin. By working on multiple parts of the coagulation system, AT helps effectively regulate clotting.
Thrombin acts on fibrinogen to form fibrin, the essential element of a clot. Fibrin is an insoluble protein that combines with other proteins to form clots. By inhibiting thrombin, antithrombin inhibits clotting. Both of these working in concert along with other clotting factors keep the coagulation system regulated.
Antithrombin deficiency causes the coagulation system to work out of control. One AT unit is needed to inhibit one thrombin unit. If AT is taken out of this equation, the proliferation of thrombin will cause the overproduction of clots. AT only has a plasma half-life of three days, so it must be produced regularly for continued effectiveness. Just a 50 percent reduction in AT is enough to unbalance the coagulation system and cause unnecessary clotting.
Clots should be produced in response to injuries but, without AT, an imbalanced coagulation system can produce clots anywhere in the circulation system. Arteries and veins can be blocked by clots. Clots can also travel in the blood stream to critical parts of the body, such as the brain or heart, leading to stroke, heart attack, or even death. Too little clotting can be just as harmful, causing patients to bleed to death from even minor injuries.
Antithrombin deficiency can be genetic or acquired. Types of genetic antithrombin deficiencies include thrombophilia and AT III deficiency. With genetic antithrombin deficiency there can be a variety of factors that lead to abnormal clotting. The type of mutation that causes the antithrombin deficiency is important. This determines whether the effects of antithrombin deficiency become apparent in early adulthood or later in life and whether the symptoms will be mild or very serious.
Some causes of acquired antithrombin deficiency include renal failure, acute respiratory distress syndrome, pregnancy, and liver disease. Infants are susceptible to antithrombin deficiency because they naturally have less AT. This can be counteracted by alpha2-macroglobulin, a protein that is naturally found in infants and also works as a thrombin inhibitor. Bone marrow transplant patients also have a higher risk of antithrombin deficiency.