Plasma levels of enoxaparin oligosaccharides, antifactor-Xa and thrombin generation in patients undergoing haemodialysis.

Abstract

: Low molecular weight heparins are used during haemodialysis for thromboprophylaxis of the dialysis circuit, with plasma antifactor-Xa (anti-Xa) activity used as a surrogate measure for effective anticoagulation. However, this pharmacokinetic parameter does not always correlate with pharmacodynamic effects in patients. The aim of this study was to investigate the relationship between actual plasma levels of the low molecular weight heparins enoxaparin, anti-Xa activity, and global coagulation measurement of thrombin generation during haemodialysis. Blood was analysed from 16 adult patients with end-stage kidney disease at 0, 2, 4 h, and at completion of 31 dialysis sessions where single fixed doses of 20 (n = 3), 40 (n = 16), 60 (n = 6), or 80 (n = 6) mg of enoxaparin (equating to 0.23-1.07 mg/kg) were used as thromboprophylaxis. Plasma enoxaparin oligosaccharides [degree of polymerization (dp)6-dp16] were measured by high-performance size exclusion chromatography, anti-Xa activity by colourimetric assay, and thrombin generation by calibrated automated thrombogram. Plasma enoxaparin fragments were undetectable at the beginning of each dialysis, peaked at 2 h to levels that correlated with dose (r = 0.68, P < 0.001) then remained relatively stable. In contrast, therapeutic anti-Xa levels achieved at 2 h in 18 cases (58%) quickly dropped to only six cases (19%) at the end of dialysis, by which time thrombin generation had also recovered in 81% of patients. Statistical modelling revealed a threshold value of anti-Xa at 0.53 IU/ml that supressed thrombin generation to 15.28% of baseline (P < 0.001). Despite loss of anticoagulant activity in the majority of patients, plasma levels of enoxaparin oligosaccharides remained detectable and relatively unchanged throughout dialysis.