ANTIPLATELET AGENTS AFFECTING THE INTERACTION OF TISSUE FACTOR FACTORVIIA COMPLEX WITH FACTOR-X IN A CONTINUOUS-FLOW REACTOR

The purpose of the present study was to examine the role of antithromb otic agents in the activation of Factor X in the presence of the Tissu e Factor-Factor VIIa (TF-VIIa) complex in a continuous-flow reactor. T issue Factor immobilized in a phospholipid bilayer on the inner surfac e of a capillary tube (internal diameter = 0.27 mm) was exposed to a p erfusate containing Factors VIIa and X flowing at a flow rate of 12.7 mu l/min, corresponding to a wall shear rate of 100 s(-1). Factor Xa ( the activated form of Factor X) in the effluent was determined by a ch romogenic assay. The effectiveness of two platelet aggregation inhibit ors, alpha,alpha'-bis-[3-(N,N-diethylcarbamoyl)piperi dino-p-xylene di hydrobromide (A-1) and alpha,alpha'-bis-[3-N- benlyl-N-methylcarbamoyl )piperidino]-p-xylene dihydrobromide (A-4) in inhibiting Factor X acti vation is reported here. The results suggest that the Tissue Factor pa thway, mediated through TF-VIIa complex, produces significantly lower levels of Factor Xa in the presence of compounds A-1 and A-4, On the b asis of these findings, it appears that the anticoagulation action of these compounds reinforces their platelet aggregation-inhibitory prope rties. These carbamoylpiperidines (nipecotamides) therefore appear to be useful antithrombotic agents.