Different effect of unfractionated heparin and enoxaparin on circulating proangiogenic factors during hemodialysis: A cross-over study

Background. We aimed to compare the effect of unfractionated heparin (UFH) and enoxaparin used as anticoagulants during hemodialysis (HD) on circulating levels of heparin-binding, endothelial-derived, proangiogenic factors-vascular endothelial (VEGF165) and basic fibroblast (bFGF) growth factor. Methods. We enrolled 22 chronic HD patients, who were randomly assigned to either enoxaparin (n = 11) or UFH (n = 11) anticoagulation, and followed prospectively for 12 weeks before crossing over to the alternate therapy for further 12 weeks. The cytokines were measured by immunoassay at the start, at 10 and 180 min of HD. Results. The baseline VEGF165 and bFGF levels were comparable during enoxaparin and UFH treatment. VEGF165 significantly decreased during both enoxaparin (χ2 ANOVA = 33.0, P < 10−6) and UFH (χ2 ANOVA = 27.2, P < 10−6) anticoagulated HD, while over-HD bFGF remained stable regardless of the type of heparin. The switch from enoxaparin to UFH treatment was connected with 34% VEGF165 decrease after 180 min of HD and had no impact on bFGF. During UFH-anticoagulated HD 75% VEGF165 decrease after 10 min was negatively associated with heparin dosage and was more profound in patients with ischemic heart disease. Conclusion. The traditional UFH regimen, in contrast to enoxaparin treatment, is connected with dose-depended VEGF165 decrease during HD procedure. The biological and possible clinical relevance of this observation requires further investigations.