Variability in platelet procoagulant activity in healthy volunteers

Blood platelets provide the major surface for thrombin generation. When platelets are activated they expose phosphatidylserine (PS) on their outer membranes, providing the surface on which two procoagulant enzyme complexes, the Xase and prothrombinase complexes, assemble. We hypothesized that there is biological variability in platelet procoagulant activity. To test this hypothesis, we activated isolated platelets from seventeen volunteers, and added plasma concentrations of factors VIII, IXa, and X for the Xase complex assembly, and F.Xa and II for the prothrombinase complex. Xase and prothrombinase activity were assayed using a chromogenic substrate. We found a two- to three-fold variation in Xase and prothrombinase activity, respectively. The distribution of Xase activity in the population was symmetric, while the distribution of prothrombinase activity was positively skewed. The difference in distribution implies that simple expression of procoagulant lipid was not the only determinant of procoagulant activity. Variation in prothrombinase activity was not due to the amount of platelet-released F.V. Neither microparticle production nor F.X binding correlated with Xase or prothrombinase activity. Using fluorescein-conjugated annexin V, we also found no direct correlation between the level of PS exposure and Xase or prothrombinase activity. This indicates that platelets must make other contributions, in addition to PS, to the activity of the Xase and prothrombinase complexes. There is evidence that platelets possess specific receptors for some coagulation proteins, although these receptors have not been isolated. Biological variability in the expression of platelet receptors might explain the differences in Xase and prothrombinase activities in our study.