Antithrombin: facts and new hypotheses.
Antithrombin (AT) is an important inhibitor of the coagulation system, acting at many different levels of the coagulation cascade. This inhibitory action is enhanced several-fold by the glycosaminoglycan heparin. AT deficiency can be encountered in hereditary disorders, which are rare, or in acquired conditions, in which there is an excessive consumption of AT. Acquired AT deficiency is a common condition in sepsis, after major trauma or surgery, with or without associated disseminated intravascular coagulation (DIC). In these conditions, low levels of AT have been correlated with a poor outcome due to the development of multiple organ failure. Although supplementation with AT has been shown to attenuate the extent of organ failure in critically ill patients, it has not been possible to significantly improve the survival of these patients by administration of AT. An interesting new approach to AT treatment is based on the hypothesis that AT has specific effects that are independent of the coagulation cascade. Data from cell culture and animal experiments have demonstrated that AT can promote the endothelial production of prostacyclin and may therefore have anti-inflammatory actions. This effect is based on the interaction of AT with glycosaminoglycans in the cell membrane, and is independent of heparin. The role of AT in vessel wall antithrombogenicity is being increasingly appreciated. The concept of neointimal hyperplasia following vascular injury involves thrombin as an important mediator and thus, in addition to the anti-inflammatory effects of AT, new horizons in which AT may have an important role in the prevention of post-traumatic hyperplastic response are also evolving.
Risberg
B
B
Department of Vascular Surgery, Sahlgrenska University Hospital, Göteborg University, Sweden. bo.risberg@surgery.gu.se
D000818:Animals; D000991:Antithrombins / Q000172:deficiency; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004211:Disseminated Intravascular Coagulation / Q000378:metabolism*; D006801:Humans; D018805:Sepsis / Q000378:metabolism*
D000991:Antithrombins