Aldea G S, O'Gara P, Shapira O M, Treanor P, Osman A, Patalis E, Arkin C, Diamond R, Babikian V, Lazar H L, Shemin R J
Department of Cardiothoracic Surgery, Boston University Medical Center, Massachusetts 02118-2393, USA.
Ann Thorac Surg. 1998 Feb;65(2):425-33. doi: 10.1016/s0003-4975(97)01347-7.
We have demonstrated that the use of heparin-bonded cardiopulmonary bypass circuits (HBCs) combined with a lower anticoagulation protocol as an adjunct to an integrated blood conservation strategy decreases the incidence and magnitude of homologous transfusion and improves clinical outcome in patients undergoing primary coronary artery bypass grafting. It is not known whether it is the lower anticoagulation protocol that influences outcome in patients treated with HBCs. Furthermore, the thrombogenic risk of using lower anticoagulation with HBCs still is debated.
To answer these questions, a prospective randomized study was conducted in which 244 patients undergoing primary coronary artery bypass grafting were treated with HBCs and randomized to undergo either a full (activated clotting time, > 450 seconds) or a lower (activated clotting time, > 250 seconds) anticoagulation protocol. In addition to clinical outcome, levels of thrombin generation markers during and after cardiopulmonary bypass were assessed in a consecutive subset of 58 patients (full anticoagulation profile = 28, lower anticoagulation profile = 30) by measuring thrombin-antithrombin complexes and prothrombin fragment 1.2. Levels of these markers also were correlated with the activated clotting time during cardiopulmonary bypass.
Preoperative and intraoperative risk profiles and other characteristics were similar in both groups, with more than 60% of patients undergoing nonelective operation. Compared with the full anticoagulation protocol group, patients in the lower anticoagulation protocol 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 hospital 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 with a lower anticoagulation protocol was not associated with any adverse clinical events. Thrombin generation increased during cardiopulmonary bypass in both treatment groups, but was unrelated to the anticoagulation protocol or the activated clotting time (r2 = 0.03). No differences between the full and lower anticoagulation protocol groups were noted in the number of microemboli detected by transcranial Doppler analyses during cardiopulmonary bypass (n = 40) or in the postoperative neurologic and neuropsychologic outcomes (n = 30).
This study definitively demonstrates that, when used appropriately, patients 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 complex and fragment 1.2 measurements), or microscopic (transcranial Doppler analyses) thromboembolic complications or for neurologic or neuropsychologic deficits.
我们已经证明,使用肝素结合体外循环回路(HBCs)并联合较低的抗凝方案作为综合血液保护策略的辅助手段,可降低初次冠状动脉旁路移植术患者同种输血的发生率和输血量,并改善临床结局。目前尚不清楚是较低的抗凝方案影响了接受HBCs治疗患者的结局。此外,使用HBCs并采用较低抗凝方案的血栓形成风险仍存在争议。
为回答这些问题,我们进行了一项前瞻性随机研究,将244例接受初次冠状动脉旁路移植术的患者采用HBCs治疗,并随机分为接受充分抗凝(活化凝血时间>450秒)或较低抗凝(活化凝血时间>250秒)方案。除临床结局外,通过测量凝血酶 - 抗凝血酶复合物和凝血酶原片段1.2,在连续的58例患者亚组(充分抗凝组 = 28例,较低抗凝组 = 30例)中评估体外循环期间及之后的凝血酶生成标志物水平。这些标志物水平也与体外循环期间的活化凝血时间相关。
两组患者的术前和术中风险概况及其他特征相似,超过60%的患者接受非择期手术。与充分抗凝方案组相比,较低抗凝方案组患者需要血液制品的可能性较小(分别为24.2%和35.8%;p = 0.047),接受的同种供体单位明显较少(分别为0.50±0.92 U和1.08±2.10 U;p = 0.005)。两个治疗组的临床结局均同样出色(但相似),较低抗凝方案组的住院时间略有缩短(分别为5.26±1.23天和5.63±1.73天;p = 0.05)。使用HBCs并采用较低抗凝方案与任何不良临床事件均无关联。两个治疗组在体外循环期间凝血酶生成均增加,但与抗凝方案或活化凝血时间无关(r2 = 0.03)。在体外循环期间通过经颅多普勒分析检测到的微栓子数量(n = 40)或术后神经和神经心理学结局(n = 30)方面,充分抗凝组和较低抗凝组之间未观察到差异。
本研究明确表明,在适当使用时,接受HBCs和较低抗凝方案治疗的患者同种输血的发生率和输血量较低,并且在临床、血液学(凝血酶 - 抗凝血酶复合物和片段1.2测量)、显微镜下(经颅多普勒分析)血栓栓塞并发症或神经或神经心理学缺陷方面没有任何额外风险。