Platelets are involved in promoting the interactions and activations of coagulation proteins at various stages of the intrinsic system, including contact activation, factor-X activation and prothrombin activation. Recent studies from our laboratory, supported by the present grant favoring this general hypothesis include the following observations: 1) platelets promote the proteolytic activation of factor XI in the presence of HMW kininogen and either factor XIIa of kallikrein; 2) activated platelets bind both factor XI and XIa tightly and specifically in the presence of HMW kininogen and enhance 10- to 40-fold the coagulant activities of both factors XI and XIa 3) the functional and structural integrity of factor XIa is fully retained when it is bound to the platelet surface; 4) the factor-Xa catalyzed activation of factor IX appears to be physiologically significant reaction as judged from kinteic parameters; 5) platelet membranes contain a molecule functionally and antigenically similar to plasma factor XI but different in molecular weight and subunit structure that may substitute for plasma factor XI in coagulation reactions and 6) the prothrombinase complex, consisting of facotr Va, factor Xa and a phospholipid cofactor, is assembled on platelet membrane components that are specifically associated with triton-insoluble cytoskeletons of activated platelets. Several lines of evident suggest the hypothesis, so far not studied directly that platelets may interact specifically with factor IX and factor IXa, thereby promoting factorX activation. Specifically, the objectives of these investigations are: 1) to investigate the binding of factor IX and factor IXa to platelets, including studies of a) time course and requirements for protein cofactors, electrolytes and divalent cations, state of platelet activation and platelet agonists; b) specificity; c) saturability and reversibility; d) derivation of binding constants. 2) To study the platelet contribution to factor-X activation, indcluding a) requirements for protein factors, electrolytes and divalent cations, state of platelet activation and platelet agonists; b) effects of phospholipids cofactor VIII and platelets on kinetics of factor X activation.
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