THROMBOELASTOGRAPHY AS AN INSTRUMENT OF PRECLINICAL STUDIES OF THE POTENTIAL DRUG

Publication date: 2020

DOI: 10.7324/JAPS.2020.10812

Abstract:

There are no recommendations for assessing the effect of potential drugs on the hemostatic system irrespective of the anticipated 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 method for 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 acute de novo thrombosis (n = 90) was used. Using activated TEG, in vitro hemostatic system hyperactivity modeling was carried out with the blood of healthy male donors (n = 20); 0.2 М CaCl2, recombinant TF, and thrombin were used as TEG 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 screening method for assessing the effect of new pharmacological agents on the hemostatic system at preclinical stage was demonstrated; the possibility of safety assessment for hypercoagulability/hypocoagulability was shown; and the comparability of hemostatic parameters of the patients with thrombosis and TEG, activated by TF and/or thrombin was demonstrated.

Тип: Article