Unfractionated heparin but not enoxaparin causes delayed plasma PAI-1 depletion in hemodialysis patients: a prospective study.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Naumnik
Beata
B
Department of Nephrology and Transplantation With Dialysis Unit, Medical University, Białystok, Poland. bnaumnik@poczta.onet.pl
Pawlak
Krystyna
K
Mys'liwiec
Michal
M
D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D019040:E-Selectin / Q000097:blood; D017984:Enoxaparin / Q000494:pharmacology*; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D006435:Renal Dialysis; D018180:Thrombomodulin / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis
D000925:Anticoagulants; D019040:E-Selectin; D017984:Enoxaparin; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D011498:Protein Precursors; D018180:Thrombomodulin; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D006493:Heparin