The Role of Platelets in Intrinsic Factor-Xa Formation

Although the essential role of phospholipid in the interaction of factors VII and IX has been demonstrated (Lundblad & Davie, 1964), detailed studies of platelet activity in intrinsic coagulation have not previously been reported. A basic test system has been developed for studying the interaction of factors XIa, VIII, IX, and X in the formation of factor Xa. Using platelets from normal and coagulation-factor-deficient donors, washed by albumin density gradient separation (ADGS), a comparative study of platelets and phospholipid in intrinsic factor-Xa formation has been done under various test conditions.
Both platelets and phospholipid (Folch) are shown here to play a part in intrinsic factor-Xa formation, whereas neither enhances extrinsic factor-Xa formation. Collagen promotes a platelet coagulant activity which increases the rate of factor-Xa formation in the test system employed. The effect of collagen depends entirely on the presence on the platelet surface of factor XI, but not of factor XII. In contrast to collagen, adenosine diphosphate has no effect on this intrinsic platelet coagulant activity. In experiments carried out in the presence of naturally-occurring inhibitors to active clotting factors (anti-factors Ila, Xa, and XIa) it is shown here that contact product is adsorbed to the platelet surface where it is protected from destruction by antifactor XIa. Factor Xa is formed subsequently by the interaction of intrinsic clotting factors, which is presumed to occur on the platelet surface since factor Xa is found in association with the platelets, not the surrounding plasma.