THE EFFECT OF IMMUNODEPLETION OF ANTITHROMBIN-III ON THE RESPONSE OF RABBITS TO RUSSELLS VIPER VENOM-INDUCED ACTIVATION OF FACTOR-X

Many years ago it was shown that an infusion of tissue factor (TF) int o rabbits causing only limited consumption of factor X and prothrombin resulted in extensive consumption of fibrinogen. More recently it was shown that an injection of a concentration of the factor X-activating fraction of Russell's viper venom (RVV-X) depleting rabbits of factor X resulted in only minimal consumption of both plasma prothrombin and fibrinogen. We report here experiments in which rabbits depleted of a ntithrombin III (ATIII) to different degrees were infused over 4 hours with a concentration of RVV-X, causing consumption of about 60% of pl asma factor X. Similar minimal mean falls in plasma prothrombin and fi brinogen levels were observed in control rabbits given nonimmune goat IgG and in rabbits immunodepleted with goat anti-rabbit ATIII IgG to a bout 40% of normal plasma ATIII activity. However, if rabbits were imm unodepleted to about 10% to 20% of normal plasma ATIII, then mean cons umption of prothrombin was increased modestly and, more impressively, mean consumption of plasma fibrinogen was increased markedly. Whereas limited amounts of thrombin generated on the surface of phospholipid v esicles by factor VIIa/TF can trigger extensive intravascular coagulat ion in rabbits with normal plasma ATIII levels, limited amounts of thr ombin generated by reactions triggered by factor Xa formed in fluid ph ase did so only after plasma ATIII levels were markedly depleted. A po ssible reason for this difference is discussed.