Thromboelastography as an instrument of preclinical studies of the potential drug

ABSTRACT

There are no recommendations for assessing the effect of potential drugs on the hemostatic system irrespective of theanticipated application area, which leads to long-term financial losses. The examples of papaverine hydrochloride,pentoxifylline, and acetylsalicylic acid demonstrated the potential of thromboelastography (TEG) as a screening methodfor products that affect the hemostatic system, the safety assessment method for hypercoagulability/hypocoagulability,and the thrombosis model, using tissue factor (TF) or thrombin. The blood of male donor patients (n = 60) with acutede novo thrombosis (n = 90) was used. Using activated TEG, in vitro hemostatic system hyperactivity modeling wascarried out with the blood of healthy male donors (n = 20); 0.2 М CaCl2, recombinant TF, and thrombin were used asTEG activators. General coagulation tendency (R), functional activity of thrombocytes and fibrinogens (МА, Angle),fibrinolysis activity, and physical–mechanical properties of formed clots were determined from thromboelastograms.The effect of anti-aggregants was characterized by a significant decrease in МА. The potential of TEG as a screeningmethod for assessing the effect of new pharmacological agents on the hemostatic system at preclinical stage wasdemonstrated; the possibility of safety assessment for hypercoagulability/hypocoagulability was shown; and thecomparability of hemostatic parameters of the patients with thrombosis and TEG, activated by TF and/or thrombinwas demonstrated.