Unfractionated Heparin but Not Enoxaparin Causes Delayed Plasma PAI-1 Depletion in Hemodialysis Patients: A Prospective Study

Abstract

Heparin modulates function of vascular endothelial cells. We studied the effects of unfractionated heparin (UFH) versus low-molecular-weight heparin (LMWH), enoxaparin, used as anticoagulants during hemodialysis (HD) on plasma levels of circulating endothelium-derived molecules: thrombomodulin (TM), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), cell surface adhesion molecules (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and prothrombin fragment 1+2 (PF 1+2). Twenty-five patients undergoing enoxaparin-anticoagulated HD were randomly assigned either to continue enoxaparin (n = 13) or receive UFH (n = 12) during HD and followed prospectively for 12 weeks. Plasma immunoreactive TM, vWF, PAI-1, ICAM-1, E-selectin, and PF 1+2 were measured before the randomization procedure and after 12 weeks, at the start, after 10 and 180 minutes of HD. The switch from LMWH to UFH resulted in decreased pre-HD levels of PAI-1 and TM and increased PF 1+2 concentrations. Predialysis PAI-1 negatively correlated with the total dose of UFH/kg/HD. No significant differences were observed in the other variables before and during HD after switching from LMWH to UFH. During enoxaparin-anticoagulated HD, only plasma PAI-1 levels decreased by 32% after 180 minutes compared with the baseline values. This percentage decrease positively correlated with predialysis PAI-1 levels and marginally with PF 1+2 concentrations after 180 minutes of enoxaparin-anticoagulated HD. Enoxaparin-anticoagulated HD is related to transient plasma PAI-1 decrease, whereas UFH anticoagulation may be the cause of delayed PAI-1 and TM depletion, which is an untoward consequence of enhanced coagulation activity in chronic HD patients.