Gryshchuk V. Vitamin K-dependent proteins of coagulation system during haemostasis disorders

The objects of the PhD-thesis were study of the role of vitamin K-dependent haemostatic proteins during the pathologies of blood coagulation; determination of their functional activity; investigation of new haemostatic nanomaterials that acts mainly on them; construction of novel test-systems for the diagnostics of thrombophilia, monitoring of indirect anticoagulants therapy and antihepatotoxicity therapy. The experimental model based on activating enzymes from the snakes' venoms was developed. It allowed us to study the action of exogenous factors on different stages of coagulation and the activation of individual factors in the whole system. Using the developed system we clarified the mechanism of haemostatic action of silica nanoparticles that consists in selective activation of coagulation factor X through intrinsic pathway coagulation proteins. This finding is promising for the development of haemostatic agents of localized action. Coagulation system of rats with drug-induced hepatitis was studied. It was shown for the first time that determining of the activity of vitamin K-dependent haemostatic proteins could be promising way to monitor antihepatotoxicity therapy. The determining of functionally active prothrombin and PIVKA-prothrombin as well as their correlation rate was shown to be a promising method to control the oppressing of procoagulant haemostasis during indirect anticoagulants which are vitamin K-antagonists. The protein C activity drop in was shown to be in direct proportion to thrombotic events. We also proved that algorithms of the diagnostics of thrombophilia have to include additional tests that allow clarifying the rate of haemostasis over-activation and contain/activity of vitamin K-dependent haemostatic proteins.