Citrate compared to low molecular weight heparin anticoagulation in chronic hemodialysis patients

Abstract

Citrate and nadroparin calcium, a low molecular weight heparin (LMWH), were compared in a randomized cross-over trial in 21 chronic hemodialysis patients regarding anticoagulation, calcium and magnesium kinetics, biocompatibility, dialysis efficiency, and aluminum contamination. Citrate was infused into the arterial line at a minimum rate of 0.68 mmol/min, combined with a calcium and magnesium-free dialysate and intravenous supplementation of calcium and magnesium at rates of 0.22 and 0.10 mmol/min, respectively. Seven patients with a dialysis session of six hours, received 2/3 of the nadroparin dose predialysis, and 1/3 after 2.5 hours (divided dose (DD) group). A single predialysis bolus injection of nadroparin was administered to eight patients not on coumarins [single dose (SD) group] and to six patients on coumarins [single dose + coumarins (SD + C) group], all with a dialysis session of four hours. Nineteen patients received a nadroparin dose of 200 ICU/kg. Two patients with a single dose, one of them on coumarins, received a dose of 150 ICU/kg because of a hematocrit < 0.30. With citrate systemic whole blood activated clotting time (ACT) remained unchanged, indicating efficient regional anticoagulation. After two hours of dialysis with nadroparin, systemic ACT increments, that is, the increase compared to predialysis, of the DD, SD, and SD + C groups were 8.8 +/- 1.5, 18.7 +/- 4.7, and 33.3 +/- 6.1 seconds, respectively (mean +/- SEM). Postdialysis ACT increments in these groups were 1.5 +/- 3.4, 17.7 +/- 6.8, and 30.3 +/- 8.0 seconds. Two hour increments of systemic activated partial thromboplastin time (APTT) of the DD, SD, and SD + C groups during nadroparin were 5.0 +/- 1.2, 15.1 +/- 2.7, and 32.2 +/- 5.5 seconds, respectively, and the corresponding postdialysis APTT increments were 2.9 +/- 1.4, 7.8 +/- 2.4, and 15.8 +/- 2.6 seconds. Two-hour anti-Xa increments of the DD, SD, and SD + C groups amounted to 0.34 +/- 0.07, 0.67 +/- 0.07, and 0.80 +/- 0.08 IU/ml. The respective postdialysis anti-Xa increments were 0.21 +/- 0.06, 0.58 +/- 0.06, and 0.71 +/- 0.08 IU/ml (All ACT, APTT and anti-Xa increments were significant; P < 0.05), except for the ACT increments and the postdialysis APTT increment of the DD group). These increments, together with unchanged prothrombin fragments 1 and 2 (PTF1 + 2), indicate systemic anticoagulation with nadroparin. The increments of serum calcium and magnesium during citrate were comparable to the increments observed with a dialysate containing 1.5 mmol/liter calcium and 0.75 mmol/liter magnesium used in combination with nadroparin. Ionized calcium increments during citrate were significant after the end of dialysis, while the dialysate containing 1.5 mmol/liter calcium induced significant increments during and postdialysis. No differences were observed between citrate and nadroparin regarding biocompatibility), (expressed as dialysis-induced leukopenia and thrombocytopenia), and dialysis efficiency [measured as dialyzer urea and creatinine clearance, normalized weekly whole body urea clearance (Kt/Vurea) and time averaged urea concentration (TACurea)]. The citrate solution, if sterilized in glass bottles, contained 2 to 3 micrograms aluminum per mmol citrate, the nadroparin solution 0.009 microgram per 1,000 ICU. Aluminum contamination of the citrate solution was prevented by sterilizing the solution in polypropylene bottles. In conclusion, citrate anticoagulation is regional and is indicated for hemodialysis patients with an active or recently active bleeding focus. However, the citrate solution should be sterilized in polypropylene containers to prevent aluminum contamination. LMWHs induce systemic anticoagulation during hemodialysis, and this effect is enhanced by concomitant coumarin use and mitigated by a divided LMWH dose regimen. For hemodialysis patients not at risk of bleeding, LMWHs provide a simple anticoagulation regimen.