EVIDENCE SUGGESTIVE OF ACTIVATION OF THE INTRINSIC PATHWAY OF BLOOD-COAGULATION AFTER INJECTION OF FACTOR XA PHOSPHOLIPID INTO RABBITS

The present study was carried out to extend an earlier observation fro m this laboratory that mean plasma factor X levels fell by about 15% a fter the injection into rabbits of a formed factor Xa/phospholipid com plex that caused only minimal intravascular coagulation. We have now i njected rabbits with formulations of factor Xa/phospholipid that cause d considerable intravascular coagulation, as documented by substantial falls in fibrinogen, factor V, and factor Vm and a fall in plasma pro thrombin activity of about 15% to 20% of the initial level. Mean plasm a factor X activity fell by about 30% of the initial level. Factors pa rticipating in the intrinsic coagulation pathway-XII, XI, and IX-all f ell by about 50% after injection of a complex made with 16.3 pmol fact or 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 phos pholipid per 1 kg body wt. Ln contrast, total plasma factor VII activi ty did not change, and specific plasma factor VIIa levels, which were lower than those measured in human plasma, did not rise after injectio n of factor Xa/phospholipid. The data are compatible with the hypothes is that factor Xa-phospholipid-induced generation of thrombin in vivo leads to factor XII-dependent activation of the intrinsic pathway of c oagulation that results in significant activation of factor X. Further testing of this hypothesis appears warranted.