Antithrombin III (AT III) or antithrombin is an endogenous serpin synthesized in the liver and one of the most important natural inhibitors of blood coagulation. It inhibits the serine proteases of the plasmatic coagulation, builds thrombin ( factor IIa) and activated proteolytically from the endothelial cells, the synthesis of t-PA ( tissue-type plasminogen ).

Antithrombin is the antagonist of thrombin. It is amplified by heparin in its effectiveness and speed (about 1,000 times ). A deficiency of antithrombin III can therefore result in a ineffectiveness of heparin or a high heparin requirements. After operations from the AT III decreases regularly. It is therefore not very suitable for detecting a consumption coagulopathy.

For substitution of AT III is administered by slow intravenous injection. AT III is obtained from fractionation recovered by blood donation human plasma protein ( antithrombin derived from human plasma, HPAT ) or isolated from the milk of genetically modified mammals (recombinant human antithrombin, Rhat ).

Antithrombin derived from human plasma

The dose of 1 IU / kg increased the AT III levels by about 1-1.5 % ( Anbinex ® solution for injection, AT III Immuno ® solution for injection, Atenativ ® injection solution).

Recombinant human antithrombin

The milk of genetically modified goats from the farms of the U.S. company GTC Biotherapeutics contains the recombinant human antithrombin, which supports the international non-proprietary name antithrombin Alfa, in a concentration of up to 10 g per liter of milk. Under the trade name ATryn ® was approved in July 2006 for the European and in February 2009 for the U.S. market for the prevention of venous thromboembolism in surgery of patients with congenital antithrombin deficiency. Label extension will be sought for patients where such a defect is not hereditary. Alfa Antithrombin is the first drug that is prepared using genetically conceived animals. GTC therefore chose goats for the process, because they reproduce faster than cattle and produce more protein than rabbits or mice, and indicates that a genetically modified goat per year can produce the same amount of antithrombin as 90,000 blood donations. The genetic manipulation is performed by microinjection of human antithrombin genes in the nucleus of a goat embryo. In parallel with the pharmaceutical regulatory committee ( pharmaceutical regulatory board) the FDA approved the Center for Veterinary Medicine of the genetic structure of the goats for drug production.


Antithrombin is a glycoprotein, whose Proteinkomponenete consists of 432 amino acids and human plasma -derived antithrombin ( HPAT ) and the recombinantly produced ( Rhat ) antithrombin Alfa is identical. There are differences, however, in its glycosylation, ie The type and number of the sugar chains, which are attached to the protein. This results in a significantly different binding affinity for heparin, the approximately four times as strong in vitro for Rhat than the HPAT.

The inhibitory activity of Rhat and HPAT on thrombin ( factor IIa) and factor Xa is about the same. It is based on the complex formation between anti-thrombin and the clotting enzyme. The formation of the complexes takes place slowly, their degradation occurs in the reticuloendothelial system. Heparin accelerates the formation of the antithrombin - clotting enzyme complex by about 1000-fold.

The antithrombin concentration in human plasma is typically from 12.5 to 15 mg / dl. The antithrombin activity of 1 ml of normal human plasma is by definition 1 International Unit ( IU) per milliliter, which is equated with 100 %.