Low molecular weight heparin in haemodialysis for chronic renal failure: dose finding study of CY222.
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)
Ireland
H
H
Department of Haematology, Charing Cross and Westminster Hospital, London, UK.
Lane
D A
DA
Flynn
A
A
Pegrum
A C
AC
Curtis
J R
JR
D004341:Drug Evaluation; D015951:Factor Xa; D005344:Fibrinopeptide A / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D006435:Renal Dialysis; D015842:Serine Proteinase Inhibitors; D001620:beta-Thromboglobulin / Q000378:metabolism
D006495:Heparin, Low-Molecular-Weight; D015842:Serine Proteinase Inhibitors; D001620:beta-Thromboglobulin; D005344:Fibrinopeptide A; D006493:Heparin; D015951:Factor Xa