Heparins and blood polymorphonuclear stimulation in haemodialysis: an expansion of the biocompatibility concept

Background. At the concentrations used in haemodialysis and in a dose-dependent way, unfractionated heparin (UFH) and, to a lesser degree, a low-molecular-weight heparin (LMWH) stimulate polymorphonuclear cells (PMN) in vitro, and could act in synergy with the stimulatory effect of dialysis membranes in vivo. To examine this hypothesis, we studied the effects of different heparin types and regimens on blood PMNs during haemodialysis sessions. Methods. Ten haemodialysed patients were studied during regular dialysis sessions on a cellulose triacetate membrane (CT 110 G; 1.10 m(2); Baxter), with four different random heparin protocols: one high-UFH regimen (HHR) at 90 IU/kg body-weight (b.w.) and one low-UFH regimen (LHR) at 50 IU/kg b.w., and with a LMWH (nadroparin calcium) at 85 (HHR) or 45 (LHR) IU/kg b.w. Blood granulocytes, platelet counts, and plasma granulocyte degranulation products (elastase, lactoferrin) were measured serially during 4 h dialysis sessions. Results. After 10 min, the reduction in PMNs with UFH: was 29.5% for HHR (P < 0.01) and 28.5% for LHR (P < 0.01), and only 16.8 and 18.6% with LMWH (NS), significantly higher for HHR with UFH than with LMWH (P < 0.01). At 60 min, the elastase increase with HHR was greater, 61% with UFH (P < 0.01) and 37.8% with LMWH (P < 0.01), significantly higher than LHR for UFH (P < 0.05) or LMWH (P < 0.05). The overall decrease in platelets (with LMWH P < 0.01) and the overall increase in lactoferrin (P < 0.001) were not different between heparinization procedures. Conclusion. Under a conventional heparin regimen, the PMN variation during the course of the dialysis session suggests a more biocompatible effect of LMWH over UFH. In addition, the variation of elastase favours the lower dose, whatever the type of heparin. Heparin type and dose should therefore be considered in studies addressing biocompatibility in haemodialysis: a low dose of LMWH may be viewed as a better biocompatible treatment with regard to leukocyte stimulation.