Evidence Suggestive of Activation of the Intrinsic Pathway of Blood Coagulation After Injection of Factor Xa/Phospholipid Into Rabbits

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Abstract
Abstract The present study was carried out to extend an earlier observation from this laboratory that mean plasma factor X levels fell by about 15% after the injection into rabbits of a formed factor Xa/phospholipid complex that caused only minimal intravascular coagulation. We have now injected rabbits with formulations of factor Xa/phospholipid that caused considerable intravascular coagulation, as documented by substantial falls in fibrinogen, factor V, and factor VIII and a fall in plasma prothrombin activity of about 15% to 20% of the initial level. Mean plasma factor X activity fell by about 30% of the initial level. Factors participating in the intrinsic coagulation pathway—XII, XI, and IX—all fell by about 50% after injection of a complex made with 16.3 pmol factor Xa and 80 nmol phospholipid per 1 kg body wt and by about 35% after injection of a complex made with 32.6 pmol factor Xa and 40 nmol phospholipid per 1 kg body wt. In contrast, total plasma factor VII activity did not change, and specific plasma factor VIIa levels, which were lower than those measured in human plasma, did not rise after injection of factor Xa/phospholipid. The data are compatible with the hypothesis that factor Xa/phospholipid–induced generation of thrombin in vivo leads to factor XII–dependent activation of the intrinsic pathway of coagulation that results in significant activation of factor X. Further testing of this hypothesis appears warranted.