EFFECT OF ANTICOAGULATION PROTOCOL ON OUTCOME IN PATIENTS UNDERGOING CABG WITH HEPARIN-BONDED CARDIOPULMONARY BYPASS CIRCUITS

Background. We have demonstrated that the use of heparin-bonded cardio pulmonary bypass circuits (HBCs) combined with a lower anticoagulation protocol as an adjunct to an integrated blood conservation strategy d ecreases the incidence and magnitude of homologous transfusion and imp roves clinical outcome in patients undergoing primary coronary artery bypass grafting. It is not known whether it is the lower anticoagulati on protocol that influences outcome in patients treated with HBCs. Fur thermore, the thrombogenic risk of using lower anticoagulation with HB Cs still is debated. Methods. To answer these questions, a prospective randomized study was conducted in which 244 patients undergoing prima ry coronary artery bypass grafting were treated with HBCs and randomiz ed to undergo either a full (activated clotting time, >450 seconds) or a lower (activated clotting time, >250 seconds) anticoagulation proto col. In addition to clinical outcome, levels of thrombin generation ma rkers during and after cardiopulmonary bypass were assessed in a conse cutive subset of 58 patients (full anticoagulation profile = 28, lower anticoagulation profile = 30) by measuring thrombin-antithrombin comp lexes and prothrombin fragment 1.2. Levels of these markers also were correlated with the activated clotting time during cardiopulmonary byp ass. Results. Preoperative and intraoperative risk profiles and other characteristics were similar in both groups, with more than 60% of pat ients undergoing nonelective operation. Compared with the full anticoa gulation protocol group, patients in the lower anticoagulation protoco l group were less likely to require blood products (24.2% versus 35.8% , respectively; p = 0.047) and received substantially fewer homologous donor units (0.50 +/- 0.92 versus 1.08 +/- 2.10 U, respectively; p = 0.005). Clinical outcomes were uniformly outstanding (but similar) in both treatment groups, with a modest reduction in the length of the ho spital stay in the lower anticoagulation protocol group (5.26 +/- 1.23 versus 5.63 +/- 1.73 days, respectively; p = 0.05). The use of HBCs w ith a lower anticoagulation protocol was not associated with any adver se clinical events. Thrombin generation increased during cardiopulmona ry bypass in both treatment groups, but was unrelated to the anticoagu lation protocol or the activated clotting time (r(2) = 0.03). No diffe rences between the full and lower anticoagulation protocol groups were noted in the number of microemboli detected by transcranial Doppler a nalyses during cardiopulmonary bypass (n = 40) or in the postoperative neurologic and neuropsychologic outcomes (n = 30). Conclusions. This study definitively demonstrates that, when used appropriately, patient s who are treated with HBCs and a lower anticoagulation protocol have a lower incidence and magnitude of homologous transfusion and are not at any added risk for clinical, hematologic (thrombin-antithrombin com plex and fragment 1.2 measurements), or microscopic (transcranial Dopp ler analyses) thromboembolic complications or for neurologic or neurop sychologic deficits.