A dose finding study of the very
low molecular weight heparin CY222 (MW 2500) in patients (n = 8) with
chronic renal failure undergoing dialysis has been carried out to (i) establish an effective dose and (ii) determine the relationship between ex vivo anti-
factor Xa levels in plasma and the
anticoagulant effect (in vivo suppression of FPA levels). Doses of
CY222 were compared to a dose (5000 iu bolus + 1500 iu/hr) of
unfractionated heparin (UFH) that has been shown to suppress FPA levels during prolonged (greater than 5 hr) dialysis (Ireland et al., J Lab Clin Med 103, 643, 1984).
CY222 given iv in increasing doses produced a dose related increase in anti-
factor Xa levels (measured as Institute Choay u/ml, with
CY222 itself as standard) and suppression of FPA levels. When given in its highest dose, 20,000 Institute Choay u bolus + 1500 Institute Choay u/hr, there was little effect upon KCCT, FPA levels were statistically indistinguishable from those of the UFH regime (indicating comparable
anticoagulant effect), but anti-
factor Xa levels (expressed in Institute Choay u/ml) were 2-3 times those of UFH (expressed in iu/ml). All samples were also assayed for anti-
factor Xa level against the proposed low MW
Heparin Standard. Plasma levels of
CY222 were then found to be 2.78 times lower, so that the anti-
factor Xa levels of
CY222 required to produce comparable
anticoagulant effect were then indistinguishable from those of UFH.(ABSTRACT TRUNCATED AT 250 WORDS)