Interaction of thrombin with mammalian platelets

Abstract

In this study we have explored the interaction of thrombin with platelets from human and rat. Compared to human platelets, rat platelets suspended in plasma required a higher concentration of thrombin for aggregation. This difference in sensitivity to thrombin was maintained when platelets were washed and suspended in buffer. Platelets from both mammals bound thrombin and showed a similar number of binding sites. However, the apparent dissociation constant of thrombin binding for rat platelets was approximately 15-fold higher than that for human. Thus, the decreased aggregation response of rat platelets may be due to a reduced binding of thrombin to its receptor. It is known that the thrombin receptor is located on the platelet surface. Gel electrophoresis of platelets followed by specific staining as well as fluorography showed significant differences in the surface glycoproteins of human and rat platelets. Human platelets showed labeled components corresponding to 210,000 and 160,000 daltons, whereas rat platelets showed glycoproteins with molecular weights of 240,000 and 190,000. A 135,000-dalton component was present in platelets from both sources. These results suggest that either or both glycoproteins of 210,000 and 160,000 daltons may be involved in the interaction of thrombin with human platelets.

Interspecies differences in coagulation profile

“…In contrasttohumans and rabbits,thrombin did not cause changes in the MCF in pigs, rats and sheep, which mayb ed ue to higher doses of thrombin required. This explanation is supported by other investigators (12)(13)(14).…”

“…Moreover, thrombin doses higher than0.2 IU did not have asignificant additionaleffect on the clotting time in anys pecies. The highest dose of thrombin wasc hosen on the basis of ap reviousr eport,w hich showedshortening in the clotting timeafter incubation of human and pigblood with 1IUofthrombin (11).These data arenovel and provide morecomplete understanding of interspeciesdifferences in the thrombin effectsoncoagulation in vitro,which add to previouslyreported species differences of thrombin effectson plateletfunction (12)(13)(14).…”

“…This observation is supportedbyprevious studiesusing different methods. Plateletsofrats were at leastfour-foldlessresponsiveto thrombin when compared to humanplatelets when aggregometry wasused (12,13). Rats were three-fold less responsivetothrombin thanh umanp latelets as measuredb yf lowc ytometry ( 14).…”

Laboratory Rat Thrombi Lose One-Third of Their Stiffness When Exposed to Large Oscillating Shear Stress Amplitudes: Contrasting Behavior to Human Clots

“…Some rat strains display platelet hyperreactivity [10], and the plasma fibrinolytic system has a higher resistance to activation [11]. On other hand, in the murine system thrombin binds less to the GpIb platelet receptor [5,12], platelets are irresponsive to the thrombin receptor activating peptide [13], and platelet aggregation cannot be triggered by adrenalin [14]. Thrombin and plasmin generation differed from humans and were reduced [15].…”