王清平¹ 薛玉良² 杜洪印¹ 翁亦齐¹ 王刚¹

Abstract  Objective: the purpose of this study is to use the thromboelastography to monitor the coagulation during orthotopic liver transplantation without veno-venous bypass, to investigate the changes of coagulopathy and to evaluate the effects of treatment during OLT.  It also analyzes the important reasons of the postreperfusion coagulopathy through thromboelastography, and finds out the best therapies. Methods： 48 patients undergoing OLT were performed general anesthesia.  The native TEG and the haparinase modified TEG were measured before the operation began (T1), 5 min before reperfusion  (T2)，5 min after reperfusion (T3), 10 min after protamine were given (T4)．The measured variables included the R (reaction) time, K (coagulation) time, Angles (reflecting fibrin-platelet interaction), MA (maximal amplitude). Results：There is no significant difference between HTEG and NTEG. at T1 and T2 time. Within 60 minutes after graft liver reperfusion (T3), None of the NTEG samples of all the groups formed effective thromboelastography, 46 of which presented a straight line. Compared with HTEG at T1 and T2, K remarkably prolonged, and meanwhile, Angle and MA significantly decreased (P<0.01). After the intravenous injection of different doses of protamine, NTEG effective thromboelastography signature at T4 resumed. As for HTEG, that were all close the level before reperfusion. Conclusion：There are several reasons caused by the postreperfusion coagulapathy. The thrombelastography has been shown as a useful monitor of coagulation during liver transplantation, and provides a rational approach for use of blood component therapy or pharmacological intervention. Exogenous heparin or heparin-like substances can be released during reperfusion, due to its administration to the donor before harvesting the graft and may contribute to critical coagulapathy. Protamine was used to eliminate heparin during postreperfusion. The use of haparinase modified TEG to monitor coagulation during OLT provides useful additional information in all groups of patients.

 [Key words]    thrombelastography  coagulation   liver transplantation heparin  heparinase   protamine  

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凝血弹性图（Thromboelastography，TEG）可以从一份血样本全面评估凝血功能，从血小板、纤维蛋白相互反应开始记录血小板和纤维蛋白凝固级联反应，包括血小板聚集、血凝块强化、纤维蛋白交叉连接，最后到血凝块溶解的整个过程。所描记的图形可提供有关凝血因子活性、血小板功能及纤维蛋白溶解过程等资料。本研究目的在于探讨使用TEG监测国内医疗环境下终末期肝病患者接受非转流异体原位肝移植手术中凝血功能的变化，分析凝血异常原因，观察药物治疗效果。特别是分析新肝期再灌注后凝血紊乱的可能原因、相关因素、使用鱼精蛋白纠正的效果，进一步探讨改善凝血的最佳治疗方案。

资料与方法

一般资料  终末期肝病行同种异体原位经典非转流肝移植肝移植患者48例，男38例，女10例。Child分级B级或C级，年龄45.4±7.6岁，体重67.4±<?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com:office:smarttags" />10.9公斤。根据新肝期再灌注后给予鱼精蛋白剂量不同，随机将病人分为P30组（鱼精蛋白30mg）；P50组（鱼精蛋白50mg）；P80组（鱼精蛋白80mg）。

麻醉方法  患者入室后静脉注射东莨菪碱0.3mg、咪唑安定0.05～0.1 mg•kg^-1，局麻下经Allen试验侧桡动脉穿刺置管测桡动脉压。静脉注射咪唑安定0.1 mg•kg^-1、舒芬太尼0.5～1 μg•kg^-1 、丙泊酚1～2 mg•kg^-1、维库溴铵0.15 mg•kg^-1行麻醉诱导。气管插管后FiO₂50％间歇正压通气。经右颈内静脉穿刺置入三腔静脉导管，两腔作为静脉通路，一腔术中采血。置入Swan-Ganz导管测中心静脉压(CVP)、肺动脉压(PA)、肺动脉毛细血管楔压(PCWP)。采用静吸复合全麻，麻醉维持采用丙泊酚复合异氟烷。调整机械通气指标，维持呼末二氧化碳在30～35 mmHg。分次追加舒芬太尼和维库溴铵，异丙酚2～6mg•kg^-1•h^-1维持麻醉。麻醉期间使用手术床加温床垫、输液加温器和辐射式加温仪，使手术各阶段患者体温不低于35℃。手术过程中按需采集中心静脉血样检测血常规、血气、出凝血功能、生化功能等指标，根据检验结果进行液体、药物治疗。不同时间点采集中心静脉血样检测TEG，根据检测结果调整输入新鲜冰冻血浆、血小板、凝血酶原复合物、纤维蛋白原、氨甲环酸及鱼精蛋白以改善凝血功能

检测方法  分别于手术开始时（T1），无肝期（肝上下腔静脉、肝下下腔静脉、门静脉完全阻断开始到门静脉开放结束）再灌注前5min（T2），新肝期（肝上下腔静脉、肝下下腔静脉、门静脉完全开放，供肝恢复血供）再灌注后5min（T3），给予鱼精蛋白后10min（T4）由右颈内静脉中心静脉导管内采血同时进行自然全血（NTEG）和含肝素酶全血（HTEG，内含4.0单位冻肝素酶）试剂杯中，使用TEG5000凝血分析仪同时进行检测，记录R（min）、K（min）、Angle（degree）、MA（mm）等数值。检测温度为37℃。各时间点采血前10min停止调整凝血功能的液体及药品输入。

统计分析  所有数据均以<?xml:namespace prefix = v ns = "urn:schemas-microsoft-com:vml" /> ±s表示，两组间比较行T检验，多组间各指标比较采用方差分析。所有资料均采用SPSS12.0统计软件包进行统计分析，P<0.05为有统计学意义。

结   果

1、病例一般情况：

   患者以及供肝一般情况、诊断构成详见表1、2。三组患者年龄、体重无统计学差异（P>0.05）。NTEG与HTEG各记录数值见图1－4。

2、T1时间点TEG监测结果：

   同正常值相比，三组患者NTEG的K值稍延长，MA值降低，HTEG的结果近似于NTEG组，且两者数值间无统计学差异（P>0.05）。见表3、4。