Effects of Ultrafiltration on Enoxaparin: An In Vitro Analysis

Abstract

The use of low molecular weight heparins (LMWH) as an anticoagulant in the heparin-resistant patient poses challenges during cardiopulmonary bypass (CPB). The ultrafiltrability of LMWH has not been previously examined. The purpose of this study was to determine the effects of continuous ultrafiltration on the concentraton of a LMWH, enoxaparin. An in vitro analysis was performed using fresh whole human blood and an extracorporeal circuit containing four parallel ultrafiltrators and a cardiotomy reservoir with an integrated heat exchanger. Constant conditions included temperature (37°C), flow (0.20 L-min−1) transmembrane pressure (200 mmHg), and hematocrit (25 ± 2%). Samples were collected at the inlet, outlet, and ultrafiltrate line at one and three min for one control trial and again for each of the four hemoconcentrators following the bolus of enoxaparin. Coagulation measurements included a viscoelastic monitor (TEG), activated clotting time (ACT), activated partial thromboplastin time (aPTT), and quantitative analysis utilizing a membrane-based electrode for potentiometric measurement of polyanionic concentrations of enoxaparin. Enoxaparin concentration, from inlet to outlet, increased from 2.95 ± 0.64 to 5.89 ± 0.95 (p < .001) at 1 min and 4.24 ± 0.49 to 7.89 ± 0.606 (p < .001) at 3 min. Kinetic clot activity, as assessed by the TEG index, decreased from −3.8 ± 2.5 vs. −10.5 ± 6.0; (p < .01) pre- to postultrafiltrator samples after 3 min. ACT and aPTT results demonstrated no significant change. In conclusions, this study demonstrates enoxaparin is concentrated with the use of continuous ultrafiltration. Functional coagulation studies also indicate a concentrating effect, primarily via the TEG.