Interaction of the sulfated lactobionic acid amide LW 10082 with thrombin and its endogenous inhibitors.
The synthetic polyanion LW 10082 prolonged thrombin clotting times when human or bovine thrombin were used to induce clotting. In the clotting time prolongation LW 10082 was 15 times more potent in the presence of human thrombin than of bovine thrombin. In an amidolytic thrombin inhibition assay, LW 10082 inhibited bovine and human thrombin when plasma was present. Here, too, thrombin inhibition was much more pronounced when human thrombin was used. When purified antithrombin III was used, neither human nor bovine thrombin were inhibited by LW 10082. LW 10082 proved to be a potent inhibitor of human thrombin in the presence of heparin cofactor II in an amidolytic assay. The time course of the inhibition was slow and at least 10 minutes of incubation were required to obtain complete inhibition of thrombin by an excess of HC II and LW 10082. The anticoagulant activity of LW 10082 in the APTT was unchanged in the presence of anti-antithrombin III antibodies while the potency of heparin was clearly reduced. This indicates that the overall anticoagulant effect of LW 10082 was as well independent of antithrombin III.
Klauser
R J
RJ
Luitpold-Werk, Chem.-pharm. Fabrik, München, Germany.
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000990:Antithrombin III / Q000378:metabolism; D002417:Cattle; D004187:Disaccharides / Q000494:pharmacology*; D015844:Heparin Cofactor II / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010314:Partial Thromboplastin Time; D013045:Species Specificity; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000925:Anticoagulants; D004187:Disaccharides; D015844:Heparin Cofactor II; D000990:Antithrombin III; D013917:Thrombin; C069690:aprosulate