Cyclic AMP independent inhibition of platelet aggregation by prostaglandin E1 is mediated through factor Xa

Normal plasma exposed to an insolublized ω-NH2-hexyl-agarose derivative of PGE₁ inhibits ADP-induced platelet aggregation. To define the plasma macromolecule responsible, we tested plasma congenitally deficient in coagulation factors for this property. Only plasma deficient in factor X failed to inhibit platelet aggregation under these conditions. The inhibition could be restored by reconstituting the defective plasma with bovine or human factor X. Purified factor X or Xa exposed to insolubilized PGE₁ also inhibited ADP-induced platelet aggregation. Factor Xa could reverse the inhibition of altered factor X but the reverse was not true suggesting that factor Xa was the responsible component. This conclusion was further supported by the ability of heparin to reverse the inhibitory effect of altered factor Xa when the anti-coagulant was added simultaneously to platelets. The results were not due to the release of PGE₁ from the insoluble derivative. Factor Xa may have a heretofore unrecognized effect on modulating platelet functions.