Antithrombin, a 58 kD, 432 amino-acid glycoprotein, belongs to the serpin (serin protease inhibitor) superfamily. It is one of the most important natural inhibitors of blood coagulation. The factors most strongly inhibited are thrombin and factor Xa, but also factors of contact activation, intrinsic system and the factor VIIa/tissue factor complex. Antithrombin activity is greatly enhanced by heparin and the anticoagulant effects of heparin depend on the presence of antithrombin. Antithrombin contains two functionally important domains. The first contains the reactive centre and provides a cleavage site for proteinases such as thrombin, a prerequisite for forming a stable proteinase-inhibitor complex. The second is a glycosaminoglycan binding domain responsible for the interaction with heparin and related substances, which accelerates the inhibition of thrombin. The inhibitor-coagulation enzyme complexes are removed by the reticulo-endothelial system. Antithrombin activity in adults is 80-120% and levels in neonates are about 40-60%.
There are several smaller studies of consumption syndrom (DIC), sepsis, preeclampsia, Lasparaginase treatment of acute lymphoblastic leukaemia, veno-occlusive disease, surgery with heart-lung machine, where antithrombin administration has shown positive effects on coagulation parameters. In the so called Kybersept study, which included more than 2300 patients with sepsis, there was no difference in mortality in those treated with antithrombin compared to placebo.
Pharmacokinetic studies with human antithrombin have shown a mean biological half life of about 3 days. The half life may be reduced to approximately 1.5 days in the case of concurrent heparin treatment.
Antithrombin contains trace amounts of the chemicals tributyl phosphate and octoxynol, which are used during manufacturing for viral inactivation. In non-clinical studies, effects of these impurities were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little clinical relevance.
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