Antithrombin III activity
Antithrombin III is a single chain glycoprotein which is synthesized in the liver and has a molecular weight of approximately 58200 daltons. AT III is a progressive inhibitor and inactivates not only thrombin (factor IIa), but also other serine proteases: predominantly factor Xa and to a lesser extent IXa, XIa, XIIa, and also plasmin and kallikrein. Heparin greatly accelerates the inactivation of IIa and Xa. The AT III concentration and the concentrations of Protein C and Protein S all play an important role in the maintenance of a hemostatic equilibrium.
Hereditary AT III deficiency with concomitant thromboembolic complications was first reported in 1965. Hereditary AT III deficiency is inherited in an autosomally dominant fashion and is prevalent in both men and women to approximately the same amount. One differentiates between two types:
• Type I‑deficiency: AT III concentrations and activities are lowered to the same extent due to decreased synthesis in the liver.
• Type II‑deficiency: AT III concentration remains normal, but its biological activity is reduced due to altered molecular structure.
Acquired AT III deficiency is much more common than hereditary AT III deficiency, but nevertheless much more rarely causes an increased risk of thrombosis. AT III concentration and activity are both decreased to the same extent. AT III deficiency can be caused by:
• Decreased synthesis due to restricted (hepatic disease) or immature functioning of the liver (newborn, premature babies). In general, all liver‑dependent coagulation factors and inhibitors are decreased to the same extent. Because of the overall balanced hemostatic equilibrium, an increased tendency to thrombosis does not arise.
• Intravasal AT III loss due to its relatively small molecular weight:
- Renal loss in the course of a nephrotic syndrome
- Enteral loss in the course of protein‑loss enteropathies
- Increased permeation into the extravasal space due to increased blood vessel permeability
• Increased loss due to elevated activation of the coagulation process or activation of coagulation over a longer period of time, e.g.
- Continuous intravenous heparin therapy
- Consumptive coagulopathy, DIC
• In the course of septic infection there is a direct relationship between AT III activity loss and the severity of the infection or the course of the sepsis. When septic disease is clinically suspected, early determination and determination in the context of disease monitoring of AT III activity is indicated to ensure early detection of DIC.
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