Prothrombin Binding” to Phospholipid Vesicle Surfaces and Phospholipid Acceleration of Prothrombin Activation

Prothrombin binds to phospholipid vesicle surfaces via the Fragment 1 region of the prothrombin molecule. The physiological importance of the direct prothrombin binding to phospholipid has been demonstrated recently in comparative studies of the activation of bovine normal and abnormal (dicoumarol “induced”) prothrombins (Esmon, C. T., Suttie, J. W. and Jackson, C. M., In Press). The binding of prothrombin and isolated Fragment 1 to vesicles composed of a variety of different phospholipids has been quantitatively investigated. From these studies it has been shown that prothrombin binding involves 20 ± 2 calcium ions and by comparison with the binding of calcium to prothrombin and Fragment 1 in free solution, this binding is consistent with association via calcium bridges between protein and lipid. Comparison of the ability of phospholipid to accelerate prothrombin activation with the affinity of prothrombin for particular phospholipid surfaces underlines the quantitative importance of the lipid-protein-calcium interaction in the activation process.

The in vitro acceleration of prothrombin activation by phospholipid surfaces which can be readily quantitated and related to protein binding to the surface provides a new set of criteria for quantitatively assessing the thrombogenicity of surfaces in general. Although providing a limited definition of and scale for thrombogenicity, the specificity of such assay provides a means by which the multiplicity of factors contributing to surface thrombogenicity may be better understood.

(Supported by a grant to Washington University, HL-14147 for a Specialized Center on Research on Thrombosis).