Dose finding study of a low molecular weight heparin, Innohep, in haemodialysis.
A pilot investigation was performed with Innohep, a low molecular weight (LMWH) preparation (peak maximum molecular mass 3,000-6,000), to determine possible dose regimens for patients undergoing regular maintenance haemodialysis for chronic renal failure. Results from this study suggested that suppression of macroscopic clot formation and fibrinopeptide A (FPA), a marker of fibrin formation, could be achieved following bolus injections rather than bolus injections and an infusion. On the basis of these preliminary findings, a randomised crossover study was performed in eight patients undergoing regular maintenance haemodialysis for 5-7 h to determine the effective antithrombotic dose of this LMWH. Single i.v. bolus doses of 1,250 AFXa u, 2,500 AFXa u and 5,000 AFXa u (n = 7-8) were compared to an UFH regime of 5,000 iu + 1,500 iu/h. Excessive clot formation in the dialyser bubble trap, necessitating additional UFH to enable completion of a prolonged (up to 7 h) dialysis, was observed in all patients on the 1,250 AFXa u dose (mean duration of dialysis prior to UFH, 3 h) but in a single patient only receiving the other LMWH doses. A dose-related response in the AFXa activity, measured by chromogenic substrate (CS) assay was seen in the three LMWH groups, with levels declining significantly (p less than 0.05) from 1-7 h. This contrasted with the constant levels maintained during dialysis with UFH. FPA levels were significantly elevated after 2 h following the 1,250 AFXa u bolus and after 4 h following the 2,500 AFXa u bolus. There was no significant difference in FPA levels between the 5,000 AFXa u bolus and UFH.(ABSTRACT TRUNCATED AT 250 WORDS)
Ryan
K E
KE
Department of Haematology, Charing Cross and Westminster Medical School, London, UK.
Lane
D A
DA
Flynn
A
A
Shepperd
J
J
Ireland
H A
HA
Curtis
J R
JR
D004305:Dose-Response Relationship, Drug; D005344:Fibrinopeptide A / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008970:Molecular Weight; D008991:Monitoring, Physiologic; D010865:Pilot Projects; D006435:Renal Dialysis / Q000379:methods*; D013923:Thromboembolism / Q000517:prevention & control*
D005344:Fibrinopeptide A; D006493:Heparin