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撤回:蛋白质C-血栓调节蛋白系统及纤维蛋白溶解在心血管手术中的作用:术前急性血浆置换的影响

RETRACTED: The role of the protein C-thrombomodulin system and fibrinolysis during cardiovascular surgery: influence of acute preoperative plasmapheresis.

作者信息

Menges Thilo, Wagner Ralf-M, Welters Ingeborg, Ruwoldt Ralph, Boldt Joachim, Hempelmann Gunter

机构信息

From the Department of Anaesthesiology and Intensive Care Medicine, Justus-Liebig-University, Giessen, Germany.

出版信息

J Cardiothorac Vasc Anesth. 1996 Jun;10(4):482-489. doi: 10.1016/S1053-0770(05)80009-6.

Abstract

OBJECTIVES

To assess the benefits of withdrawn autologous plasma, the objective of this study was to investigate whether withdrawal of acutely performed platelet-rich or platelet-poor plasmapheresis allays changes in the protein C-thrombomodulin and fibrinolytic systems after retransfusion secondary to cardiopulmonary bypass (CPB). In addition, the study attempted to determine the influence of acute plasmapheresis (APP) on the protein C-thrombomodulin and fibrinolytic systems as well as on homologous blood consumption and perioperative blood loss in elective aortocoronary bypass patients.

DESIGN

The investigation was scheduled as a prospective, randomized, unblinded study.

SETTING

This single investigation was conducted in the Department of Anesthesiology and Intensive Care Medicine at a university in Germany. The study protocol was approved by the Ethics Committee of the hospital, and informed consent was obtained.

PARTICIPANTS

Sixty male patients scheduled for elective coronary artery bypass grafting with extracorporeal circulation were included in the study.

INTERVENTIONS

APP was performed between induction of anesthesia and incision, collecting either 10 mL/kg of autologous platelet-poor plasma (PPP patients, group 1; n = 20) or the same amount of platelet-rich plasma (PRP patients, group 2; n = 20). Patients of group 3 (n = 20) had no APP (control group). All patients were maintained on their usual regimen of cardiac drugs until the morning of surgery. To preserve hemodynamic stability and restore the intravascular oncotic pressure, the separated plasma was replaced by infusion of an equal amount of hydroxyethyl starch solution (HES) (6% HES, molecular weight 2 x 10(5), substitution rate 0.5%). In all operations, the same surgical procedure was chosen. For all patients, induction and maintenance of anesthesia were similar, consisting of weight-related doses of fentanyl (35 micrograms/kg), midazolam (0.65 mg/kg), and pancuronium bromide (0.15 mg/kg). The lungs of all patients were mechanically ventilated during the first 5 hours after the end of the operation.

MEASUREMENTS AND MAIN RESULTS

All patients had serial coagulation studies including antithrombin (AT) III-activity, prekallikrein, factor XII, and immunologic tests such as thrombin-antithrombin III (TAT), fibrinopeptide A (FPA), protein C and S (PC and PS), thrombomodulin (TM), tissue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PAI 1), fibrinopeptide B beta 15-42 (FPB beta 15-42), D-dimers, and hemoglobin and platelet counts determined intraoperatively and postoperatively. Chest tube drainage and transfusion requirements were recorded. APP had no negative effects on the quality of PPP and PRP plasma. The platelet count of the withdrawn plasma was 28 +/- 12 x 10(9)/L (PPP group) and 245 +/- 36 x 10(9)/L (PRP group). At the end of the operation (after retransfusion of autologous plasma) and on the morning of the first postoperative day, platelet counts were significantly higher (p > 0.05) in the PRP than in the PPP and control groups. Plasma concentrations of TAT and FPA increased (ranging from +185% to +340% from baseline values) and AT III-activity, PC, PS, and TM antigen decreased (ranging from -8% to -55% from baseline values) to a different extent for all three groups throughout CPB. t-PA-activity increased with a maximum at the end of CPB (PPP group, 6.9 +/- 1.5 IU/mL: PRP group, 3.8 +/- 0.8 IU/mL; control group, 10.9 +/- 2.8 IU/mL). Fibrin and fibrinogen degradation markers such as D-dimers and FPB beta 15 to 42 occurred in peak concentrations after neutralization of heparin by protamine. Only PRP patients showed baseline concentrations of coagulation parameters the next morning (p < 0.05). Total postoperative blood loss within the first 24 hours reached 482 +/- 273 mL (PRP group), 775 +/- 256 mL (PPP group), and 948 +/- 342 mL in the control group (p < 0.05).(ABSTRACT TRUNCATED)

摘要

目的

为评估回收自体血浆的益处,本研究旨在调查急性进行的富血小板或贫血小板血浆置换术能否减轻体外循环(CPB)后再输血引起的蛋白C - 血栓调节蛋白及纤溶系统的变化。此外,该研究试图确定急性血浆置换术(APP)对择期主动脉冠状动脉搭桥患者的蛋白C - 血栓调节蛋白及纤溶系统、同种异体血消耗量和围手术期失血量的影响。

设计

该研究计划为前瞻性、随机、非盲法研究。

设置

本单中心研究在德国一所大学的麻醉与重症医学科进行。研究方案经医院伦理委员会批准,并获得了知情同意。

参与者

60例计划行体外循环择期冠状动脉搭桥术的男性患者纳入研究。

干预措施

在麻醉诱导至切口期间进行APP,采集10 mL/kg自体贫血小板血浆(PPP患者,第1组;n = 20)或等量富血小板血浆(PRP患者,第2组;n = 20)。第3组患者(n = 20)未进行APP(对照组)。所有患者直至手术当日上午均维持常规心脏药物治疗。为维持血流动力学稳定并恢复血管内胶体渗透压,分离出的血浆用等量羟乙基淀粉溶液(HES)(6% HES,分子量2×10⁵,取代率0.5%)输注替代。所有手术均选择相同的手术方式。所有患者的麻醉诱导和维持相似,包括按体重给予剂量的芬太尼(35μg/kg)、咪达唑仑(0.65mg/kg)和泮库溴铵(0.15mg/kg)。所有患者在手术结束后的前5小时进行机械通气。

测量指标及主要结果

所有患者均进行了系列凝血研究,包括抗凝血酶(AT)III活性、前激肽释放酶、因子XII,以及免疫检测,如凝血酶 - 抗凝血酶III(TAT)、纤维蛋白肽A(FPA)、蛋白C和S(PC和PS)、血栓调节蛋白(TM)、组织型纤溶酶原激活剂(t - PA)、纤溶酶原激活剂抑制剂(PAI 1)、纤维蛋白肽Bβ15 - 42(FPBβ15 - 42)、D - 二聚体,以及术中及术后测定血红蛋白和血小板计数。记录胸腔引流管引流量和输血需求。APP对PPP和PRP血浆质量无负面影响。回收血浆的血小板计数在PPP组为28±12×10⁹/L,PRP组为245±36×10⁹/L。手术结束时(自体血浆再输血后)及术后第1天早晨,PRP组的血小板计数显著高于PPP组和对照组(p > 0.05)。在整个CPB过程中,所有三组的TAT和FPA血浆浓度均升高(较基线值升高185%至340%)且AT III活性、PC、PS和TM抗原均不同程度降低(较基线值降低8%至55%)。t - PA活性升高,在CPB结束时达到最大值(PPP组,6.9±1.5 IU/mL;PRP组,3.8±0.8 IU/mL;对照组,10.9±2.8 IU/mL)。纤维蛋白和纤维蛋白原降解标志物,如D - 二聚体和FPBβ15至42在鱼精蛋白中和肝素后达到峰值浓度。仅PRP组患者在次日早晨凝血参数达到基线浓度(p < 0.05)[摘要截断]

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