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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:861.)
© 2005 American Heart Association, Inc.

Thrombosis

Platelet Heterogeneity

Variation in Coagulation Complexes on Platelet Subpopulations

Christine L. Kempton; Maureane Hoffman; Harold R. Roberts; Dougald M. Monroe

From the University of North Carolina, Chapel Hill, Department of Medicine, Division of Hematology-Oncology (C.L.K., H.R.R., D.M.M.); and Durham Veterans Affairs Medical Center (M.H.), Department of Pathology, Carolina Cardiovascular Biology Center, North Carolina.

Correspondence to Dr Dougald M. Monroe, University of North Carolina, 932 Mary Ellen Jones Building, CB 7035, Chapel Hill, NC 27599-7035. E-mail dmonroe{at}med.unc.edu

Objective— Previous work has shown that platelets stimulated with the combination of thrombin and convulxin, a glycoprotein VI agonist, develop 2 populations with different levels of -granule factor V bound to the platelet surface. To evaluate whether this phenomenon is restricted to -granule components or is a feature that can be generalized to other coagulation factors, we studied the binding of factors V, VIII, IX, and X on the surface of platelets stimulated by convulxin and thrombin.

Methods and Results— The relative amount of factors V, VIII, IX, and X on the surface of platelets stimulated with thrombin or convulxin plus thrombin was measured using flow cytometry. Simultaneous measurements of factor Xa and thrombin generation were obtained and correlated with the binding of coagulation factors on the platelet surface. The binding of factors V, VIII, IX, and X all increased on a subpopulation of platelets when stimulated with the combined agonists. The development of this platelet subpopulation is dependent on convulxin concentration and correlates with increases in factor Xa and thrombin generation.

Conclusions— The development of increased coagulation factor binding to a subpopulation of platelets is not limited to -granule components. Convulxin-induced increases in thrombin generation are regulated by the proportion of platelets with increased coagulation factor binding.

Platelets stimulated with convulxin plus thrombin compared with thrombin alone develop a subpopulation with increased surface binding of FV, VIII, IX, and X that is dependent on the concentration of convulxin and is correlated with increases in factor Xa and thrombin generation. These findings suggest that the proportion of platelets in the high-binding subpopulation regulates the degree of thrombin generation in the presence of convulxin.

Key Words: thrombin generation • platelets • glycoprotein VI • COAT • platelet subpopulation

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