Antithrombin-iii

Antithrombin III is a central antagonist or inhibitor of serine proteases. Antithrombin III inhibits all serine proteases, i.e. thrombin, factors VIIa, IXa, Xa, XIa, XIIa and kallikrein. Antithrombin III has no influence on the coenzymes factor V and VIII.

The synthesis of antithrombin takes place in the liver. The influence of antithrombin on clotting is relatively inert. It is greatly accelerated by the presence of heparin, which is why AT-III is also known as the heparin cofactor. Quantitatively, antithrombin III has the strongest inhibitory effect on thrombin and factor Xa. Together with heparin, the effect of AT-III is multiplied a thousand fold, so that thrombin is immediately blocked.

A decrease in AT-III activity to 50-70% is associated with a significantly increased risk of thrombosis. The measurement is performed with chromogenic substrate or immunologically e.g. by immuno-diffusion. AT-III is bound to thrombin and forms the so-called thrombin-antithrombin-III complex (TAT) in a ratio of 1:1. The thrombin-antithrombin complexes are an indirect measure of thrombin production and thus of clotting activity. By determining the TAT in plasma, coagulation activation can be detected before the equilibrium of hemostasis is shifted. Venous thrombosis and pulmonary embolism are associated with an increase in TAT in 80-90% of cases. In the case of disseminated intravascular coagulation, TAT is one of the most sensitive parameters of a consumption coagulopathy.

The determination is performed by ELISA ("enzyme-linked immunosorbent assay") with thrombin and AT-II-antibody in the solid phase conjugated to peroxidase. In case of hypercoagulability the TAT is increased. The reference range of the TAT is between 1.0 and 4.1 ug/l.

Causes for an increase in the thrombin-antithrombin-III complex (TAT) are:

• Occlusive diseases
• Coagulopathy of use
• Polytraumas
• large wound areas
• septic shock
• acute liver failure
• acute heart attack
• fibrinolytic therapy

Laboratory values: The standard value in serum is 75 to 120%.

Pathologically decreased: in severe hepatitis, nephrotic syndrome, sepsis, intravascular coagulation, liver cirrhosis, estrogen therapy, congenital.

1. HA Neumann (2014) The coagulation system. ABW-Wissenschaftsverlag GmbH Berlin S. 94f.