Contact activation of prekallikrein and of fibrinolysis by heparinoids and heparin.
Contact activation of plasma prekallikrein (PPK) assayed by a tripeptide chromogenic substrate, and surface-mediated fibrinolysis by the euglobulin test (both tests being insensitive to the anticoagulant effect of heparin and heparinoids) were studied. The following substances were tested: Dextran solutions of different molecular weight (M.W.), heparinoids such as dextran sulphate, pentosan and mannuronate sulphuric polyesters. Liquoid and Moranyl and various commercial therapeutic preparations of heparin. Most of these anionic polyesters are able to activate both PPK and fibrinolysis, dextran sulphate (500,000 M.W.) being the most active. Factor XII, PPK and HMWK are necessary for full activation. Besides dextran sulphate, other heparinoids such as Na pentosan polysulphate, or Na polyanhydromannuronic sulphuric acid, are also contact activators. This may explain some of their side effects observed in vivo. Non-sulphated dextrans used in therapy have no activating effect. Nine therapeutic commercial preparations of heparin were tested. They appear to have a slight activating effect on PPK but an uncertain effect on fibrinolysis. Such factor XII activability has until now been unnoticed, being masked by the anticoagulant activity of heparinoids and heparins on later phases of blood coagulation. It appears that heparin is unable to prevent contact activation in vivo as well as in vitro. This allows PPK assays during extracorporeal circulation in the presence of circulating heparin.
D003911:Dextrans / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006496:Heparinoids / Q000494:pharmacology*; D007610:Kallikreins / Q000378:metabolism*; D008722:Methods; D010958:Plasminogen / Q000378:metabolism; D011288:Prekallikrein / Q000378:metabolism*
D003911:Dextrans; D006496:Heparinoids; D010958:Plasminogen; D006493:Heparin; D011288:Prekallikrein; D007610:Kallikreins