Anticoagulant, antithrombotic and antihemostatic activities of heparin: structural requeriments, mechanism of action and clinical applications

RESUMO

The structural features for the anticoagulant, antithrombotic and antihemostatic activities of the heparin molecule as well as the resulting clinical applications are reviewed. For anticlotting activity, an intact heparin molecule with a minimum molecular weight of 8 kDa is necessary. On the other hand, for the antithrombotic activity, a heparin hexasaccharide fragment already exhibits 60 percent of the activity of heparin. Also compounds like heparan sulfate, without anticlotting activity, show the same antithrombotic effect of heparin. Heparin, besides its favorable anticoagulant and antithrombotic actions, has also a strong hemorrhagic activity. This effect is related to special structures of the damaged vessel wall and is not related to the anticoagulant and antithromboic actions. The minimum structure for the production of hemorrhage is a disaccharide composed of glucosamine C-6 sulfate and uronic acid with and 1 (4 glycosidic linkage. The hemorrhagic effect of heparin and fragments, including disaccharides, is abolished by ATP and/or myosin. The hemorrhagic disaccharides resemble the molecular conformation of ATP. Topical use of ATP in patients subjected to cardiovascular surgery with extracorporeal circulation significantly reduced the blood loss caused by heparin.