Korolova D. Prothrombin derivatives and their role in coagulant haemostasis functioning

Role of prothrombin derivatives (meizothrombin and prethrombin 1) in the fibrin and platelet clot formation process has been studied. Method of meizothrombin production that is suitable for use in model systems in vitro was developed. Meizothrombin is shown to promote fibrin network by fibrinogen coagulation and clotting factor XIII activation. It is shown by flow cytometry that meizothrombin but not prethrombin 1 is strong platelet activator in population of platelets mechanically stimulated for activation. These prothrombin derivatives are found to modulate АDР-, collagen- and adrenalin-induced platelet aggregation. Meizothrombin reduces lag-phase of collagen-induced platelet aggregation and increases rate of АDР- and adrenalin-induced platelet aggregation. Prethrombin 1 reduces induced platelet aggregation and doesn't influence on their degranulation process. Diagnostic test based on ecamulin (prothrombin activator from Echis multisquamatis venom) for detection of total prothrombin level and its functionally inactive forms (prethrombin 1 and PIVKA-prothrombin) in blood plasma is worked out. It is shown that prethrombin 1 detection could be thrombophilia a marker during systemic lupus erythematosus. Proposed diagnostic test permits to select individual dosage of oral anticoagulants for each certain patient and control efficiency of provided treatment. Thus, investigation of prothrombin derivatives gives information for clearing up pathway of hemostasis system regulation and for developing of this system state diagnostics methods.