Evaluation of the Contribution of Platelets to Clot Strength by Thromboelastography in Rabbits: The Role of Tissue Factor and Cytochalasin D

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Abstract
The contribution of platelets and soluble clotting components to clot strength has been the focus of several clinical studies using thromboelastography; it would, therefore, be beneficial to develop an animal model with which to mechanistically approach hemostatic disorders. Thus, we proposed to determine if the contribution of platelet function (GP, dyne/cm2) and soluble components of the coagulation pathway to total clot strength (GT) in rabbits were similar to those in humans. Blood was sampled from the ear arteries of conscious rabbits (n = 12); 350 μL of the blood was placed in a thromboelastograph. Ten microliters of normal saline, cytochalasin D (an inhibitor of microtubule function, 10 μM final concentration), or tissue factor (a potent stimulator of platelet function, 0.00625% final concentration) was added to the blood sample, and thromboelastography performed for 1 h. The GT (mean ± sd) was significantly (P < 0.001) different among samples exposed to normal saline, cytochalasin D, or tissue factor, with GT values of 7238 ± 1432, 937 ± 372, and 16,556 ± 3314, respectively. GP was responsible for 87% and 94% of GT in the absence or presence of tissue factor, respectively. GP did not significantly correlate with platelet concentration in the absence or presence of tissue factor. The contribution of GP to GT is similar to that observed in humans. Implications Rabbits may serve as a model of hemostasis that closely approximates human situations to mechanistically determine the etiology of coagulopathy. The contribution of platelet function to total clot strength is similar to that observed in humans.