Relationship between ex vivo anti-proteinase (factor Xa and thrombin) assays and in vivo anticoagulant effect of very low molecular weight heparin, CY222.

There is uncertainty as to which activities of unfractionated heparin (UFH) and low MW heparin are responsible for their anticoagulant and antithrombotic properties. We have sought to answer this question by examining plasma samples taken during a recently conducted dose-finding study of the low MW heparin, CY222, in haemodialysis for chronic renal failure. In this study, in vivo anticoagulant effect was assessed by measurement of plasma FPA levels. UFH was administered as a dose of 5000 iu bolus + 1,500 iu/h maintenance infusion, while the effects of three doses of CY222 were studied (10,000, 15,000 and 20,000 Institute Choay anti-factor Xa u bolus, all with 1,500 Institute Choay anti-factor Xa u/h maintenance infusion). Anti-factor Xa levels were determined by chromogenic substrate assay. Anti-thrombin levels were determined by chromogenic substrate assay and by quantitation of catalysed thrombin-inhibitor complexes (using autoradiography). Analysis of the results indicate that plasma fibrinopeptide A (FPA) levels correlate with anti-factor Xa (r = -0.45) and anti-thrombin (substrate) (r = -0.63) levels of UFH, but only with the anti-factor Xa levels (r = -0.41) of CY222. These results suggest that the anti-factor Xa assay is currently the most suitable assay for monitoring low MW heparins such as CY222 in humans.