title: Heparin clearance profiles after systemic anticoagulation using a heparin removal device system.
abstract: An extracorporeal heparin removal device system (HRDS) based on plasma separation and affinity adsorption has been developed to reduce the risks of protamine-related adverse reactions. The heparin clearance profile of the HRDS was characterized by the first-order exponential depletion. A mathematical model was established to predict the time to achieve 85% heparin removal for different body weights at 700 ml/min and 1400 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 for 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 = 10) model of 60-min, hypothermic (28 degrees C) cardiopulmonary bypass (CPB). Animals were given 300 U/kg intravenous heparin and 5000 U heparin in the circuit prime for initial heparinization, with subsequent heparin given to maintain activated clotting time above 450 sec. Immediately following CPB, plasma heparin concentration as determined by anti-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/min for animals above 75 kg. The mean body weight in the 1400 ml/min group (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 HRDS flow 658.5 +/- 20.8 and 1437.4 +/- 30.1 ml/min, respectively. During the HRDS run, plasma heparin concentration followed the predicted first-order exponential depletion (r2 = 0.97 for the 700 ml/min group and r2 = 0.99 for the 1400 ml/min group). In the 700 ml/min group, the time needed to achieve 85% heparin clearance was over 40 min, whereas 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 removal.
authors.affiliation: Department of Surgery, University of Texas Medical Branch, Galveston 77555-0528, USA.
authors.forename: W
authors.initials: W
authors.lastname: Tao
authors.forename: J D
authors.initials: JD
authors.lastname: Callahan
authors.forename: R A
authors.initials: RA
authors.lastname: Vertrees
authors.forename: R L
authors.initials: RL
authors.lastname: Brunston
authors.forename: D J
authors.initials: DJ
authors.lastname: Deyo
authors.forename: J C
authors.initials: JC
authors.lastname: McRea
authors.forename: J B
authors.initials: JB
authors.lastname: Zwischenberger
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000097:blood* / Q000302:isolation & purification*; D001783:Blood Flow Velocity; D002315:Cardiopulmonary Bypass; D002417:Cattle; D005069:Evaluation Studies as Topic; D005112:Extracorporeal Circulation / Q000295:instrumentation*; D005260:Female; D006493:Heparin / Q000097:blood* / Q000302:isolation & purification*; D066298:In Vitro Techniques; D008433:Mathematics; D008954:Models, Biological; D013552:Swine
chemical_list: D000925:Anticoagulants; D006493:Heparin