Comparative Analysis of the Hemostasiological Profile in Sheep and Patients with Cardiovascular Pathology as the Basis for Predicting Thrombotic Risks During Preclinical Tests of Vascular Prostheses

Abstract

The aim of the investigation was to study the details of hemostasiological profile in sheep and patients with coronary heart disease (CHD) and to find the possibility of predicting thrombotic risks during preclinical tests of vascular prostheses on a large laboratory animal model. Materials and Methods. The functional activity of platelets was measured in platelet-rich plasma with inductors: ADP, epinephrine, collagen. Prothrombin activity, international normalized ratio, activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration, antithrombin III and protein C activity, fibrinolysis were determined in blood plasma. Changes in clot formation and viscoelastic properties of clots were assessed using thromboelastography. Results. Significant differences were found in the hemostasiological profile of sheep and CHD patients. Sheep platelets had increased response to ADP induction and practically no response to epinephrine induction; collagen-induced aggregation was comparable in the study groups. Coagulation hemostasis of sheep was characterized by increased activity of the prothrombin complex, shortened thrombin time, while APTT and fibrinogen values remained comparable. At the same time, sheep exhibited a significant decrease in the activity of anticoagulant and fibrinolytic systems as compared to CHD patients. When assessing dynamic changes in clot formation, it was observed that initiation phase was faster in animals, while clot density exceeded that in patients. Conclusion. The hemostasiological profile of sheep is characterized by the increased speed of thrombus formation, greater strength of the formed clot, and lower lysis ability as compared to CHD patients. The revealed details of the hemostasiological profile of sheep can be potential targets for therapy with antithrombotic drugs that minimize thrombotic risks in preclinical testing of vascular prostheses.

Difference in coagulation systems of large animal species used in cardiovascular research: a systematic review

“…The measured parameters were compared to normal human references. A higher value of platelets was observed in sheep (327,200-550,700/ml vs. 150,000-450,000/ml) and is confirmed in other studies where platelets were 2 to 4 times higher [3,4,6]. Fibrinogen (with 1.78-2.15 g/dl in sheep and 180-350 g/dl in humans), vWF (101.5-118.05 IU/dl vs. 50.00-150.00 IU/dl) and aPTT (30.74-35.26 s vs. 26.00-35.00 s) did not significantly differ.…”

“…Finally, when analyzing clotting tests, we found different results for the PT going from 9-13 s in the study of Foley et al up to 21 s in the study of Siller-Matula et al which is around 2 times higher [5,6]. Gruzdeva [3,4].…”

“…(70.00-120.00 IU/dl) [3]. They observed a fibrinogen concentration of 1.80-3.50 g/l and all other studies had a value within this range [3][4][5][6]. Finally, when analyzing clotting tests, we found different results for the PT going from 9-13 s in the study of Foley et al up to 21 s in the study of Siller-Matula et al which is around 2 times higher [5,6].…”

“…Wilhelmi et al reported human platelets to be in the range of 150-450 × 10 3 /ml [3]. All platelet values found in other studies lay within this range with the exception of the results of Foley et al, who report a normal value of 140-400 × 10 3 /ml and so a slightly decreased lower limit of normal [4][5][6][7][8]. For blood hematocrit, there is an overlap between the results.…”

“…Another study comparing sheep and coronary heart disease patients found an antithrombin reduction of 13% and a protein C reduction of 72% in sheep [4]. The antithrombin activity and protein C activity were 1.2 and 3.5 times lower (p < 0.05) and the fibrinolytic activity of sheep blood plasma was 60% lower than in CHD patients (p < 0.05) [4].…”