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Antiplatelet agents affecting the interaction of Tissue Factor‐Factor VIIa complex with Factor X in a continuous‐flow reactor
Author(s) -
Gir S.,
Reavis R.,
VT Turitto,
Gollamudi R.
Publication year - 1996
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1111/j.1470-8744.1996.tb00364.x
Subject(s) - tissue factor , factor x , chemistry , factor viia , phospholipid , recombinant factor viia , antithrombotic , thrombogenicity , biophysics , factor vii , thrombin , platelet , coagulation , stereochemistry , biochemistry , medicine , biology , membrane
The purpose of the present study was to examine the role of antithrombotic agents in the activation of Factor X in the presence of the Tissue Factor‐Factor VIIa (TF‐VIIa) complex in a continuous‐flow reactor. Tissue Factor immobilized in a phospholipid bilayer on the inner surface of a capillary tube (internal diameter = 0.27 mm) was exposed to a perfusate containing Factors VIIa and X flowing at a flow rate of 12.7 microliters/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 chromogenic assay. The effectiveness of two platelet aggregation inhibitors, alpha,alpha'‐bis‐[3‐(N,N‐diethylcarbamoyl)piperidino‐p‐xylene dihydrobromide (A‐1) and alpha,alpha'‐bis‐[3‐N‐benzyl‐N‐methylcarbamoyl)piperidino]‐p‐xylen e dihydrobromide (A‐4) in inhibiting Factor X activation is reported here. The results suggest that the Tissue Factor pathway, mediated through TF‐VIIa complex, produces significantly lower levels of Factor Xa in the presence of compounds A‐1 and A‐4. On the basis of these findings, it appears that the anticoagulation action of these compounds reinforces their platelet aggregation‐inhibitory properties. These carbamoylpiperidines (nipecotamides) therefore appear to be useful antithrombotic agents.