HEPARIN CLEARANCE PROFILES AFTER SYSTEMIC ANTICOAGULATION USING A HEPARIN REMOVAL DEVICE SYSTEM

An extracorporeal heparin removal device system (HRDS) based on plasma separation and affinity adsorption has been developed to reduce the r isks of protamine-related adverse reactions. The heparin clearance pro file of the HRDS was characterized by the first-order exponential depl etion. A mathematical model was established to predict the time to ach ieve 85% heparin removal for different body weights at 70 m//min and 1 400 ml/min extracorporeal HRDS blood flow. With an HRDS flow of 700 ml , 85% of total body heparin removal cannot be achieved within 30 min f or subjects greater than 50 kg. With an HRDS flow of 1400 ml/min, 85% heparin removal can be achieved within 32 min for subjects larger than 90 kg. Such model predictions were validated in an adult swine (n = 1 0) model of 60-min, hypothermic (28 degrees C) cardiopulmonary bypass (CPB). Animals were given 300 U/kg intravenous heparin and 5000 U hepa rin in the circuit prime for initial heparinization, with subsequent h eparin given to maintain activated clotting time above 450 sec. Immedi ately following CPB, plasma heparin concentration as determined by ant i-factor Xa assays was 4.40 +/- 1.08 U/ml in the 700 ml/min group and 4.78 +/- 0.70 U/ml in the 1400 ml/min groups, respectively (p > 0.05). Target HRDS flow was 700 ml/min for animals below 75 kg and 1400 ml/m in for animals above 75 kg. The mean body weight in the 1400 ml/min gr oup (81.4 +/- 3.7 kg) was significantly higher than that in the 700 ml /min group (67.2 +/- 2.2 kg) (p < 0.05), with the actually achieved HR DS flow 658.5 +/- 20.8 and 1437.4 +/- 30.1 ml/min, respectively. Durin g the HRDS run, plasma heparin concentration followed the predicted fi rst-order exponential depletion (r(2) = 0.97 for the 700 ml/min group and r(2) = 0.99 for the 1400 ml/min group). In the 700 mi/min group, t he time needed to achieve 85% heparin clearance was over 40 min, where as in the 1400 ml/min group, this time was reduced to less than 30 min despite greater body weight. At 30 min on HRDS, the 700 ml/min group had 27.4 +/- 3.7% heparin left in the plasma, whereas the 1400 ml/min group had only 12.6 +/- 2.5% (p < 0.05). The authors conclude heparin clearance by the HRDS can be precisely predicted with the mathematical model of first-order exponential depletion. Increasing the HRDS flow can effectively reduce the time needed to achieve a targeted heparin r emoval.