原发性肝癌患者血栓弹力图的临床特征及其对凝血功能的评估价值
DOI: 10.12449/JCH260113
Thromboelastographic features of patients with primary liver cancer and their value in assessing coagulation function
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摘要:
目的 通过分析原发性肝癌患者血栓弹力图参数的临床特征,探讨其在评估凝血功能中的临床应用价值,进而为肝癌患者凝血管理及预后判断提供依据。 方法 回顾性纳入西安交通大学第一附属医院2015年5月—2022年12月收治的1 253例原发性肝癌患者,其中非肝硬化组262例、肝硬化组991例;HBV感染1 055例,非HBV感染198例。根据肝硬化程度[蔡尔德-皮尤分级(Child-Pugh分级)、终末期肝病模型(MELD)评分]和肝脏储备功能[吲哚菁绿15 min滞留率(ICGR15)]进行分类,采用血栓弹力图仪检测血栓弹力图参数(反应时间、凝血块形成时间、凝固角、最大振幅和凝血综合指数)及传统凝血指标。符合正态分布的计量资料2组间比较采用成组t检验;多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。不符合正态分布的计量资料2组间比较Mann-Whitney U检验;多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Bonferroni校正法。计数资料2组间比较采用χ2检验,相关性分析采用Spearman检验。 结果 非肝硬化组262例患者中Child-Pugh A级(5~6分)826例,B级(7~9分)165例;MELD评分<10分812例,≥10分179例;ICGR15<10% 679例,≥10% 294例。与Child-Pugh A级患者相比,Child-Pugh B级患者的凝血块形成时间显著延长,凝固角、最大振幅、凝血综合指数显著降低(P值均<0.001);与MELD评分<10分患者比较,MELD评分≥10分患者的凝血块形成时间显著延长,凝固角、最大振幅、凝血综合指数显著降低(P值均<0.001);与ICGR15<10%患者比较,ICGR15≥10%患者的凝血块形成时间显著延长,最大振幅显著降低(P值均<0.001)。1 253例患者中,最大振幅与纤维蛋白原和血小板计数均呈强正相关(r值分别为0.675、0.667,P值均<0.001);最大振幅与Child-Pugh评分、MELD评分及ICGR15呈弱负相关(r值分别为-0.112、-0.250和-0.117,P值均<0.001);凝血块形成时间、凝固角及凝血综合指数与MELD评分呈弱相关(r值分别为0.222、-0.184、-0.183,P值均<0.001);反应时间与ICGR15呈负相关(r=-0.080,P=0.005)。HBV感染组的最大振幅和凝血综合指数显著高于非HBV感染组(P值均<0.05)。 结论 血栓弹力图可敏感识别原发性肝癌患者肝硬化进展相关的低凝状态及HBV相关肝癌的高凝倾向,为临床个体化抗凝治疗提供重要参考依据。 Abstract:Objective To investigate the clinical application value of thromboelastographic parameters in assessing coagulation function by analyzing the thromboelastographic features of patients with primary liver cancer (PLC), and to provide a basis for coagulation management and prognostic evaluation in liver cancer patients. Methods A retrospective analysis was performed for 1 253 PLC patients who were admitted to The First Affiliated Hospital of Xi’an Jiaotong University from May 2015 to December 2022. According to the presence or absence of cirrhosis, the patients were divided into non-cirrhosis group with 262 patients and cirrhosis group with 991 patients, and according to the presence or absence of HBV infection, they were divided into HBV infection group with 1 055 patients and non-HBV infection group with 198 patients. The patients were stratified based on the severity of liver cirrhosis (Child-Pugh class and MELD score) and liver reserve function (indocyanine green retention rate at 15 minutes [ICGR15]), and thromboelastography was used to measure thromboelastographic parameters (reaction time [R], coagulation formation time [K], α-angle, maximum thrombosis amplitude [MA], and coagulation composite index [CI]) and conventional coagulation markers. The t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Kruskal-Wallis H test was used for comparison between multiple groups, and the Bonferroni correction method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between grouips, and the Spearman test was used for correlation analysis. Results Among the 991 patients in the cirrhosis group, 826 had Child-Pugh class A (5 — 6 points), and 165 had Child-Pugh class B (7 — 9 points); 812 had an MELD score of <10, and 179 had an MELD score of ≥10; 679 had an ICGR15 of <10%, and 294 had an ICGR15 of ≥10%. Compared with the patients with Child-Pugh class A, the patients with Child-Pugh class B had a significantly longer K time and significant reductions in α-angle, MA, and CI (all P <0.001); compared with the MELD score <10 group, the MELD score ≥10 group had a significantly longer K time and significant reductions in α-angle, MA, and CI (all P<0.001); compared with the ICGR15 <10% group, the ICGR15 ≥10% group had a significantly longer K time and a significant reduction in MA (both P <0.001). Among the 1 253 patients, MA was strongly positively correlated with fibrinogen and platelet count (r=0.675 and 0.667, both P<0.001); The MA had a weak correlation with Child-Pugh score, MELD score, and ICGR15 (r=-0.112, -0.250, and -0.117, all P<0.001), while the K time,α-angle and CI were weakly correlated with the MELD score (r=0.222, -0.184, and -0.183, all P<0.001),R time was negatively correlated with ICGR15 (r=-0.080, P=0.005). The HBV infection group had significantly higher MA and CI than the non-HBV infection group (P<0.05). Conclusion Thromboelastography can sensitively identify the hypocoagulable state associated with the progression of liver cirrhosis and the hypercoagulable tendency in HBV-related liver cancer, which provides an important reference for individualized anticoagulant therapy in clinical practice. -
Key words:
- Liver Neoplasms /
- Liver Cirrhosis /
- Hepatitis B Virus /
- Coagulation Function
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表 1 患者基线资料比较
Table 1. Comparison of baseline characteristics between groups
指标 非肝硬化组(n=262) 肝硬化组(n=991) 统计值 P值 年龄(岁) 56.26±12.02 54.96±10.52 t=1.721 0.086 性别[(例)%] χ2=8.820 0.003 男 191(72.9) 805(81.2) 女 71(27.1) 186(18.8) 病因[(例)%] χ2=25.714 <0.001 HBV 195(74.4) 860(86.8) HCV 8(3.1) 63(6.4) HBV+HCV 3(1.1) 38(3.8) 其他 56(21.4) 30(3.0) 原发性肝癌类型[(例)%] χ2=178.304 <0.001 肝细胞癌 189(72.1) 964(97.3) 胆管细胞癌 73(27.9) 27(2.7) 肿瘤直径(cm) 6.87±3.93 5.44±3.46 t=5.270 <0.001 肿瘤数量[(例)%] χ2=11.666 0.112 单发 196(74.8) 648(65.4) 多发(≥2个) 66(25.2) 343(34.6) 丙氨酸氨基转移酶(U/L) 28.0(18.0~45.8) 29.0(20.0~48.0) Z=-0.691 0.490 天冬氨酸氨基转移酶(U/L) 29.0(21.0~46.0) 32.0(24.0~51.0) Z=-0.287 0.004 总胆红素(μmol/L) 12.1(9.2~17.3) 13.8(10.1~21.5) Z=-3.892 <0.001 白蛋白(g/L) 37.44±4.91 37.21±4.78 t=0.688 0.492 注:HBV,乙型肝炎病毒;HCV,丙型肝炎病毒。
表 2 不同Child-Pugh分级患者TEG参数比较
Table 2. Comparison of TEG parameters by Child-Pugh score
TEG参数 非肝硬化组
(n=262)肝硬化组 统计值 P值 Child-Pugh A级(n=826) Child-Pugh B级(n=165) 反应时间(min) 5.67±1.10 5.87±1.31 5.72±1.15 F=2.915 0.055 凝血块形成时间(min) 1.7(1.4~2.2) 2.3(1.8~2.8)1) 2.6(2.0~3.3)1)2) H=85.231 <0.001 凝固角(degree) 65.19±7.31 60.08±10.831) 59.35±10.571)2) F=27.782 <0.001 最大振幅(mm) 61.62±7.31 55.41±7.591) 53.07±10.711)2) F=76.103 <0.001 凝血综合指数 0.3(-0.9~1.5) -1.2(-2.5~0.1)1) -1.4(-3.2~0.5)1)2) H=92.456 <0.001 注:与非肝硬化组比较,1)P<0.05;与Child-Pugh A级比较,2)P<0.05。Child-Pugh分级,蔡尔德-皮尤分级;TEG,血栓弹力图。
表 3 不同MELD评分患者TEG参数比较
Table 3. Comparison of TEG parameters by MELD
TEG参数 非肝硬化组
(n=262)肝硬化组 统计值 P值 MELD评分<10分(n=812) MELD评分≥10分(n=179) 反应时间(min) 5.67±1.10 5.84±1.29 5.85±1.28 F=1.936 0.145 凝血块形成时间(min) 1.7(1.4~2.2) 2.3(1.8~2.8)1) 2.9(2.2~3.8)1)2) H=125.677 <0.001 凝固角(degree) 65.19±7.31 60.67±10.751) 56.72±10.381)2) F=39.171 <0.001 最大振幅(mm) 61.62±7.31 55.93±7.561) 50.86±9.781)2) F=103.508 <0.001 凝血综合指数 0.3(-0.9~1.5) -1.1(-2.4~0.2)1) -2.1(-3.8~-0.5)1)2) H=118.903 <0.001 注:与非肝硬化组比较,1)P<0.05;与MELD<10分比较,2)P<0.05。MELD,终末期肝病模型;TEG,血栓弹力图。
表 4 不同ICGR15水平患者TEG参数比较
Table 4. Comparison of TEG parameters by ICGR15 levels
TEG参数 ICGR15<10%(n=697) ICGR15≥10%(n=294) 统计值 P值 反应时间(min) 5.90±1.28 5.72±1.29 t=2.043 0.041 凝血块形成时间(min) 2.39(1.80~2.80) 2.81(2.00~3.50) Z=-5.112 <0.001 凝固角(degree) 60.38±11.12 58.85±10.07 t=2.108 0.035 最大振幅(mm) 55.98±7.32 52.84±9.71 t=4.968 <0.001 凝血综合指数 -1.13±2.23 -1.53±2.86 t=2.106 0.036 注:TEG,血栓弹力图;ICGR15,吲哚菁绿15 min滞留率。
表 5 TEG参数与传统凝血指标的相关性分析(整体人群)
Table 5. Correlations between TEG parameters and conventional coagulation parameters in overall population
TEG参数 PT INR FIB D二聚体 血小板 r值 P值 r值 P值 r值 P值 r值 P值 r值 P值 反应时间 -0.006 0.826 -0.019 0.494 -0.090 0.002 -0.186 <0.001 -0.102 <0.001 凝血块形成时间 0.210 <0.001 0.244 <0.001 -0.600 <0.001 -0.265 <0.001 -0.544 <0.001 凝固角 -0.176 <0.001 -0.209 <0.001 0.569 <0.001 0.288 <0.001 0.505 <0.001 最大振幅 -0.265 <0.001 -0.304 <0.001 0.675 <0.001 0.281 <0.001 0.667 <0.001 凝血综合指数 -0.191 <0.001 -0.221 <0.001 0.576 <0.001 0.302 <0.001 0.541 <0.001 注:TEG,血栓弹力图;PT,凝血酶原时间;INR,国际化标准比值;FIB,纤维蛋白原。
表 6 TEG参数与肝功能评分的相关性分析(整体人群)
Table 6. Correlation between TEG parameters and liver function scores in overall population
TEG参数 Child-Pugh评分 MELD评分 ICGR15 r值 P值 r值 P值 r值 P值 反应时间 -0.014 0.655 -0.044 0.165 -0.080 0.005 凝血块形成时间 0.056 0.078 0.222 <0.001 0.052 0.068 凝固角 -0.027 0.395 -0.184 <0.001 -0.016 0.575 最大振幅 -0.112 <0.001 -0.250 <0.001 -0.117 <0.001 凝血综合指数 -0.059 0.063 -0.183 <0.001 -0.044 0.124 注:TEG,血栓弹力图;Child-Pugh评分,蔡尔德-皮尤评分;MELD,终末期肝病模型;ICGR15,吲哚菁绿15 min滞留率。
表 7 HBV感染组与非HBV感染组TEG参数比较
Table 7. Comparison of TEG parameters between HBV-infected and non-HBV-infected groups
TEG参数 HBV感染组
(n=1 055)非HBV感染组
(n=198)t值 P值 反应时间(min) 5.83±1.28 5.79±1.26 0.402 0.688 凝血块形成时间(min) 2.48±1.20 2.52±1.15 -0.452 0.651 凝固角(degree) 60.35±10.65 59.88±10.94 0.594 0.553 最大振幅(mm) 56.2±7.8 53.1±8.4 4.521 0.012 凝血综合指数 -1.18±2.51 -1.65±2.89 1.897 0.058 注:TEG,血栓弹力图;HBV,乙型肝炎病毒。
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