THE ACTIVITY OF UNFRACTIONATED HEPARIN AND LOW-MOLECULAR-WEIGHT HEPARINS IN RABBIT PLASMA - THE NEED FOR USING ABSOLUTE ANTI-FACTOR XA AND ANTITHROMBIN ACTIVITIES

Rabbit being a common animal model to evaluate the antithrombotic effe ct of heparins, our purpose was to apply the heparin Standard Independ ent Unit (SIU) approach to rabbit plasma. To take into account the spe cificities of the enzymes we have measured the decay constants of fact or Xa and of thrombin from autologous and heterologous origins, in pre sence and in absence of heparin. Different heparins or heparin fractio ns with a mean molecular weight from 1.7 to 10.5 kDa were used. We fou nd that: a) the decay constants varied strongly between species and be tween enzymes; b) the decay constants of thrombin were always higher t han those of factor Xa; c) the specific anti-factor Xa activity of hep arins increased with the molecular weight and was 1.33 times higher wh en determined with bovine factor Xa than with rabbit factor Xa; d) the specific antithrombin activity of heparins also increased with the mo lecular weight but was similar when determined with rabbit and human t hrombin; e) the specific anti-factor Xa activity was always lower than the specific antithrombin activity; f) the calibration of the heparin s and heparin fractions against the 4th International Standard of Hepa rin expressed in International Units (IU) lead to a systematic overest imation of the anti-factor Xa activity and to an underestimation of th e antithrombin activity. These observations indicate that it may be ve ry important to use the SIU approach and to know the accurate activiti es to better understand the mechanism of the antithrombotic activity o f heparins in experimental models.