Mahla Elisabeth, Prueller Florian, Farzi Sylvia, Pregartner Gudrun, Raggam Reinhard B, Beran Elisabeth, Toller Wolfgang, Berghold Andrea, Tantry Udaya S, Gurbel Paul A
Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Ann Thorac Surg. 2016 Dec;102(6):2010-2017. doi: 10.1016/j.athoracsur.2016.05.003. Epub 2016 Jul 1.
Up to 15% of patients require coronary artery bypass grafting (CABG) during dual antiplatelet therapy. Available evidence suggests an association between platelet reactivity and CABG-related bleeding. However, platelet reactivity cutoffs for bleeding remain elusive. We sought to explore the association between platelet reactivity and bleeding.
Patients on aspirin and a P2Y receptor inhibitor within 48 hours before isolated CABG (n = 149) were enrolled in this prospective study. Blood was drawn 2 to 4 hours preoperatively and platelet reactivity assessed by light transmittance aggregometry (LTA), vasodilator-stimulated phosphoprotein (VASP) assay, Multiplate analyzer and Innovance PFA2Y. The primary endpoint was calculated red blood cell loss computed as follows: (blood volume × preoperative hematocrit × 0.91) - (blood volume × hematocrit × 0.91 on postoperative day 5) + (mL of transfused red blood cells × 0.59).
Preoperative platelet reactivity was low [median (interquartile range): LTA: 20 (9-28)%; VASP-PRI: 39 (15-73)%; Multiplate adenosine phosphate test: 16 (12-22) U∗min]. Innovance PFA2Y ≥300 seconds, 72%. Median (IQR) red blood cell loss in patients in first the LTA tertile was 1,449 (1,020 to 1,754) mL compared with 1,107 (858 to 1,512) mL and 1,075 (811 to 1,269) mL in those in the second and third tertiles, respectively (p < 0.004). Bleeding Academic Research Consortium (BARC)-4 bleeding differed between tertiles (62% versus 46% versus 36%; p = 0.037). In a multivariable linear regression model, aspirin dose ≥300 mg, cardiopulmonary bypass time, EuroSCORE, and tertile distribution of platelet reactivity were significantly associated with red blood cell loss.
A gradual decrease in red blood cell loss and BARC-4 bleeding occurs with increasing platelet reactivity in patients on antiplatelet therapy undergoing CABG. Our findings support current guidelines to determine time of surgery based on an objective measurement of platelet function (Platelet Inhibition and Bleeding in Patients Undergoing Emergent Cardiac Surgery; clinicaltrials.gov NCT01468597).
高达15%的患者在双重抗血小板治疗期间需要进行冠状动脉旁路移植术（CABG）。现有证据表明血小板反应性与CABG相关出血之间存在关联。然而，出血的血小板反应性临界值仍不明确。我们试图探讨血小板反应性与出血之间的关联。
本前瞻性研究纳入了在孤立性CABG术前48小时内服用阿司匹林和P2Y受体抑制剂的患者（n = 149）。术前2至4小时采集血液，通过透光率聚集法（LTA）、血管扩张剂刺激磷蛋白（VASP）测定、Multiplate分析仪和Innovance PFA2Y评估血小板反应性。主要终点为计算得出的红细胞损失量，计算方法如下：（血容量×术前血细胞比容×0.91） - （血容量×术后第5天血细胞比容×0.91） + （输注红细胞毫升数×0.59）。
术前血小板反应性较低[中位数（四分位间距）：LTA：20（9 - 28）%；VASP - PRI：39（15 - 73）%；Multiplate磷酸腺苷试验：16（12 - 22）U∗min]。Innovance PFA2Y≥300秒的患者占72%。LTA三分位数中第一组患者的红细胞损失量中位数（IQR）为1449（1020至1754）mL，而第二组和第三组患者分别为1107（858至1512）mL和1075（811至1269）mL（p < 0.004）。出血学术研究联盟（BARC）-4级出血在三分位数之间存在差异（62%对46%对36%；p = 0.037）。在多变量线性回归模型中，阿司匹林剂量≥300 mg、体外循环时间、欧洲心脏手术风险评估系统（EuroSCORE）以及血小板反应性的三分位数分布与红细胞损失量显著相关。
在接受CABG的抗血小板治疗患者中，随着血小板反应性增加，红细胞损失量和BARC - 4级出血逐渐减少。我们的研究结果支持当前基于血小板功能客观测量来确定手术时间的指南（急诊心脏手术患者的血小板抑制与出血；clinicaltrials.gov NCT01468597）。
