SummaryA 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 <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. β-thromboglobulin (pTG) levels rose significantly towards the end of dialysis in all LMWH groups and, at 5 h, were significantly increased following the 5,000 AFXa u and 2,500 AFXa u doses when compared to the UFH regime. AFXa levels correlated negatively with FPA levels (r = -0.62; p <0.01). In conclusion, for administration of Innohep, a bolus dose of 2,500 AFXa u would appear to be sufficient for dialyses of short duration (up to 4 h), whilst a 5,000 AFXa u bolus is as effective as UFH for a 6 h dialysis. AFXa activity measured by CS assay is related to inhibition of fibrin formation and can be used for monitoring purposes.
No abstract
SummaryThe therapeutic potential of the glycosaminoglycan (GAG), dermatan sulphate (DS), as an antithrombotic agent in humans has yet to be established. We have performed dose ranging studies of DS to determine its effectiveness as an antithrombotic agent in patients (n = 6–8) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2–4 mg/kg and 5–6 mg/kg DS were given to patients dialysing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i. v. bolus doses of 3 mg/kg and 6 mg/kg DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efficacy of an i. v. DS bolus of 3 mg/kg plus an i. v. infusion of DS 0.6 mg kg-1 h-1 and a DS bolus of 5 mg/ kg plus an infusion of 1 mg kg-1 h-1 over 5 h, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. Plasma levels of fibrinopeptide A (FPA) and thrombin-antithrombin (TAT) were used as markers of fibrin formation and thrombin generation during dialysis using both membranes.The changes in DS concentration following administration of the different doses were similar in Studies 1 and 2. However, the effectiveness of DS as an anticoagulant appeared to depend markedly on the different dialyser types used in the two studies. In Study 1, 13/14 dialyses required additional UFH to complete a normal ~6 h session and DS was unable to prevent thrombin and fibrin formation, as determined by measurement of plasma FPA and TAT. However, some dose related effects were observed in the levels of these markers. Furthermore, DS levels correlated with those of FPA and TAT. In Study 2, increasing doses of DS (3 mg/kg and 6 mg/kg), allowed longer dialysis sessions (mean 4.57 h c.f. 5.25 h), approaching that obtained with UFH regime (5.86 h). FPA and TAT generation were incompletely suppressed by both doses of DS; FPA rose significantly compared to that observed with the UFH regime, while TAT did not. While no significant differences in the activation markers were observed between the two DS doses, DS levels, taken as a whole, showed significant negative correlations with those of FPA and TAT Little effect on the KCCT was seen.In Study 3, 3/6 patients required additional UFH (mean dialysis duration with DS 4.33 h c. f. 5.67 h with UFH). Mean DS levels were maintained between 35–40 µg/ml. Mean plasma FPA levels were maintained at constant levels throughout dialysis following DS administration but were higher than those observed following the UFH regime. In Study 4 mean DS levels were
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.