Effects of enoxaparin on myeloperoxidase release during hemodialysis

Abstract

Myeloperoxidase (MPO) is a proteolytic and prooxidant enzyme largely assembled with the vascular wall, and a heparin-binding protein. We studied if low-molecular-weight heparin enoxaparin administered for hemodialysis (HD) anticoagulation causes systemic MPO activation. Plasma MPO levels were measured in patients undergoing maintenance HD with an intravenous bolus of enoxaparin. Patients were retested during HD employing dialyzers with heparin-grafted polyacrylonitrile membrane and no systemic enoxaparin administration. During enoxaparin-anticoagulated HD plasma MPO levels strikingly increased in all patients (8.6-fold at 10 minutes and 3.3-fold at 120 minutes, both P < 0.0001). The increments were directly associated with the enoxaparin dosage and strongly inversely with the predialysis levels of the enzyme. The increase in plasma MPO during systemic heparin-free HD was significantly less pronounced. Enoxaparin administered for HD anticoagulation induces a marked and dose-dependent increase in plasma MPO as a plausibly favorable result of the liberation of the enzyme from the vascular wall.

Unexpected and striking effect of heparin-free dialysis on cytokine release

“…Other cytokines studied during Evodial dialysis were interleukin 6 (Il-6), tumor necrosis factor-α (TNF-α) [18] and myeloperoxidase (MPO) [17]. Il-6 and TNF-α levels remained stable during dialysis, but MPO levels were significantly lower.…”

“…The protocol was approved by local bioethics committee, and all individual participants signed informed consent before entering the study. The study was a prospective one planned initially to study the effect of heparin-free dialysis on myeloperoxidase release [17]; for this study, frozen samples were used (19 for MCP-1 and endostatin and 12 for activin A).…”

Extracellular superoxide dismutase release by enoxaparin and sparing effect of heparin‐grafted hemodialyzer

“…1 The MPO increase was minimal during HD employing heparin-coated dialyzer membrane and no systemic heparin. The study provided for the first time evidence that ENX releases the prooxidant and proatherosclerotic MPO enzyme from the vascular wall also during HD procedures.…”

“…In the recent article published in this journal, we reported on the striking increase in plasma myeloperoxidase (MPO) during hemodialysis (HD) procedure anticoagulated with enoxaparin (ENX). 1 The MPO increase was minimal during HD employing heparin-coated dialyzer membrane and no systemic heparin. The study provided for the first time evidence that ENX releases the prooxidant and proatherosclerotic MPO enzyme from the vascular wall also during HD procedures.…”

“…Several risk factors for vascular calcification have been proposed: transformation of vascular smooth muscle cells into chondrocyte or osteoblast-like cell, high total cumulative calcium and phosphorus in the body, impaired renal excretion, and high dietary phosphorus and calcium load. 1 Advanced age cannot be held responsible per se for this amount of calcification in the absence of CKD. This widespread calcification is, unfortunately, associated with increased morbidity and mortality.…”