急性失代偿肝硬化合并感染的凝血异常： 基于血栓弹力图的前瞻性观察性研究

张睿清; 蔡淑敏; 蒋秀华; 黄健明; 黎倍伶; 陈金军

doi:10.12449/JCH250516

急性失代偿肝硬化合并感染的凝血异常：基于血栓弹力图的前瞻性观察性研究

DOI: 10.12449/JCH250516

a.
南方医科大学南方医院肝病中心，广州 510515
b.
南方医科大学南方医院重症监护室，广州 510515

基金项目:

国家重点研发专项 (2022YFC2304800)

伦理学声明：本研究方案修正案于2022年11月11日经由南方医科大学南方医院伦理委员会审批，批号：NFEC-202003-k7-03。所有患者均签署知情同意书。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：张睿清负责数据收集，统计学分析，绘制图表，撰写文稿；蒋秀华负责指导研究思路，设计论文框架，论文修改；黎倍伶负责指导患者收集，设计患者方案；蔡淑敏负责随访患者，数据收集；黄健明负责数据收集；陈金军负责确定写作思路，指导文章撰写及最后定稿。

详细信息

通信作者:
陈金军， chjj@smu.edu.cn （ORCID： 0000-0003-4275-9149）

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出版历程
- 收稿日期: 2024-05-05
- 录用日期: 2024-07-15
- 出版日期: 2025-05-25

Coagulation abnormalities in acute decompensated cirrhosis comorbid with infection： A prospective observational study based on thromboelastography

a.
Hepatology Center, Nanfang Hospital，Southern Medical University，Guangzhou 510515，China
b.
Department of Intensive Care Unit, Nanfang Hospital，Southern Medical University，Guangzhou 510515，China

Research funding:

National Key Research and Development Program (2022YFC2304800)

More Information

Corresponding author: CHEN Jinjun， chjj@smu.edu.cn （ORCID： 0000-0003-4275-9149）

摘要

摘要: 目的观察急性失代偿期肝硬化（ADC）患者伴或不伴脓毒血症时的凝血系统变化，并探讨这些变化与短期预后的关系。方法前瞻性纳入2021年1月—2023年7月在南方医院就诊的ADC住院患者116例，其中合并脓毒血症者86例，未合并脓毒血症者30例，同时纳入无慢性肝病的单纯脓毒血症患者54例作为对照组。通过血栓弹力图（TEG）及其他常规凝血指标全面评估患者的凝血功能。收集TEG测试结果及患者的短期预后等数据，并进行相关性分析。正态分布的计量资料两组间比较采用成组t检验；非正态分布的计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ²检验。采用Spearman相关系数评估不同变量间的相关性。采用Logistic回归模型进行单因素及多因素分析。结果在ADC合并脓毒血症的患者中，感染部位以肺部和血流为主，细菌为主要病原微生物。TEG检测结果显示，与单纯脓毒血症患者比较，ADC合并脓毒血症患者的MA值中位数显著降低，K时间显著延长，α角显著减小（P值均<0.05）；与单纯ADC患者相比，ADC合并脓毒血症患者的R时间显著延长（P=0.02），而单纯脓毒血症患者的R时间高于ADC合并脓毒血症患者（P=0.04）。在ADC合并脓毒血症患者中，MA值与血小板计数无相关性（r=-0.133，P=0.057），但在单纯脓毒血症患者中显著相关（r=0.595，P=0.001）；SOFA评分与MA值在伴或不伴ADC的脓毒血症患者中均呈负相关（r值分别为-0.503、-0.561，P值均<0.001），而ADC合并脓毒血症患者的R时间、K时间和α角与SOFA评分相关性较弱，与APTT相关性较强（P值均<0.05）。单纯ADC患者90天内全部存活，而单纯脓毒血症存活患者的MA值和α角均显著高于死亡组（P值均<0.05）；无论是否合并ADC，α角在90天生存与死亡组间均差异显著（P值均<0.01），但ADC合并脓毒血症组的MA值在90天生存与死亡组间差异无统计学意义（P>0.05）。结论对于合并脓毒血症的ADC患者，临床上应重视凝血系统功能的评估和监测，必要时进行TEG相应指标和器官衰竭评分的监测，以制订个体化的治疗方案。
- 肝硬化 /
- 血液凝固 /
- 脓毒症 /
- 血栓弹力图
Abstract: Objective To investigate the changes in coagulation system in acute decompensated cirrhosis （ADC） patients with or without sepsis and the association of these changes with short-term prognosis. Methods A prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023， among whom there were 86 patients with sepsis and 30 patients without sepsis， and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography （TEG） and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected， and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. Results For the ADC patients with sepsis， the lungs and bloodstream were the main infection sites， and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone， the patients with ADC and sepsis had a significant reduction in median maximum amplitude （MA）， a significant increase in coagulation time （K time）， and a significant reduction in α angle （all P<0.05）； the patients with ADC and sepsis had a significantly longer reaction time （R time） than those with ADC alone （P=0.02）， and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis （P=0.04）. There was no correlation between MA and platelet count in the patients with ADC and sepsis （r=-0.133， P=0.057）， while there was a significant correlation between MA and platelet count in the patients with sepsis alone （r=0.595， P=0.001）. SOFA score was negatively correlated with MA in sepsis patients with or without ADC （r=-0.503 and -0.561， both P<0.001）， and for the patients with ADC and sepsis， R time， K time， and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT （all P<0.05）. The patients with ADC alone all survived within 90 days， and compared with the death group， the patients with sepsis alone who survived had significantly higher values of MA and α angle （all P<0.05）； there was a significant difference in α angle on day 90 between the survival group and the death group， no matter whether the patients were comorbid with ADC or not （both P<0.01）， while for the patients with ADC and sepsis， there was no significant difference in MA value on day 90 between the survival group and the death group （P>0.05）. Conclusion For ADC patients comorbid with sepsis， coagulation function assessment and monitoring should be taken seriously in clinical practice， and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.
- Liver Cirrhosis /
- Blood Coagulation /
- Sepsis /
- Thromboelastogram

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图 1 患者入组流程图

Figure 1. Flow chart of patients inclusion

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图 2 3组患者TEG数据比较

Figure 2. Comparison of TEG data among three groups of patients

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注： a，ADC+脓毒血症患者；b，单纯脓毒血症患者。红色代表正相关，蓝色代表负相关，颜色深浅反映了相关性的强弱，每一格的数字代表相关系数。

图 3 是否合并ADC的脓毒血症患者TEG数据和实验室指标的相关值热图

Figure 3. R-value heat maps of TEG data and laboratory indexes of sepsis patients with or without ADC

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注： a，28天预后；b，90天预后。

图 4 是否合并ADC的脓毒血症患者28天和90天预后与MA及α角数值的关系

Figure 4. The relationship between 28-day and 90-day prognosis and MA and α angle values in infected patients with ADC or without ADC

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图 5 是否合并ADC的脓毒血症患者28天预后与K时间和R时间的关系

Figure 5. The relationship between 28-day prognosis and K time and R time in infected patients with ADC or without ADC

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表 1 3组患者基线特征

Table 1. Baseline characteristics of three groups of patients

项目	ADC+脓毒血症组（n=86）	单纯ADC组（n=30）	单纯脓毒血症组（n=54）
年龄（岁）	49（41～56）	51（45～62）	62（52～73）
男［例（%）］	67（77.9）	24（80.0）	27（50.0）
器官衰竭（例）
肝衰竭	32	2	8
循环衰竭	6	0	17
呼吸衰竭	8	0	16
心衰竭	2	0	10
肾衰竭	3	0	12
大脑衰竭	14	0	4
SOFA评分（分）	4（3～6）	3（3～4）	7（3～10）
APACHEⅡ评分（分）	6（3～9）	3（2～4）	18（11～27）
实验室指标
白细胞（×10⁹/L）	7.2（4.4～10.0）	3.5（2.8～5.8）	11.8（8.6～21.5）
中性粒细胞（×10⁹/L）	4.2（2.6～6.3）	1.7（1.2～3.2）	9.7（5.9～17.4）
血小板（×10⁹/L）	73（56～110）	52（41～63）	113（70～288）
总胆红素（μmol/L）	307（68～465）	72（35～258）	25（10～67）
血肌酐（μmol/L）	76（59～104）	67（54～83）	106（69～231）
C反应蛋白（mg/L）	12.4（6.0～22.1）	5.7（2.3～10.8）	64.7（27.7～149.5）
凝血酶原时间（s）	23.8（15.4～28.2）	18.4（16.0～19.7）	13.5（12.3～15.4）
INR	2.15（1.38～2.57）	1.64（1.42～1.75）	1.17（1.06～1.34）
纤维蛋白原（g/L）	1.5（0.9～2.0）	1.3（1.2～1.7）	3.4（2.0～4.8）
D-Dimer（μg/mL）	3.3（1.9～4.8）	1.7（0.6～4.1）	5.6（3.8～8.4）
TEG参数
MA值（mm）	29.4（18.6～40.7）	31.6（25.1～39.9）	42.3（27.8～63.4）
R时间（s）	5.4（4.2～6.5）	4.9（4.2～5.5）	5.3（4.2～7.2）
K时间（s）	2.9（1.9～4.2）	3.9（2.6～5.1）	1.2（1.2～2.2）
α角（°）	56.7（46.3～64.6）	53.1（47.8～59.5）	69.8（61.1～73.7）

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表 2 ADC+脓毒血症患者和单纯脓毒血症患者感染情况

Table 2. Different infection situations between acute decompensation cirrhosis and simple sepsis patients

项目	ADC+脓毒血症组（n=86）	单纯脓毒血症组（n=54）
感染部位［例（%）］
肺部感染	42（48.8）	32（59.3）
泌尿系感染	8（9.3）	10（18.5）
血培养	16（18.6）	28（51.9）
腹膜感染	16（18.6）	7（13.0）
其他	14（16.3）	12（22.2）
微生物学［例（%）］
革兰阴性菌	22（25.6）	21（38.9）
革兰阳性菌	24（27.9）	24（44.4）
病毒	8（9.3）	8（14.8）
真菌	9（10.5）	15（27.8）
其他	19（22.1）	10（18.5）
两种以上	30（34.9）	34（63.0）

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表 3 ADC+脓毒血症患者28天及90天病死率的Logistic回归分析

Table 3. Logistic regression analysis of 28-day and 90-day mortality in patients with ADC complicated with sepsis

项目	单因素分析			多因素分析
项目	HR	95%CI	P值	HR	95%CI	P值
28天
年龄	0.897	0.844～0.913	0.572	0.913	0.844～0.988	0.023
AST	0.988	0.970～0.995	0.001	0.983	0.970～0.995	0.007
APTT	0.964	0.813～0.979	0.040	0.892	0.813～0.979	0.017
α角	1.025	0.993～1.135	0.189	1.062	0.993～1.135	0.079
90天
年龄	0.907	0.812～0.962	0.141	0.884	0.812～0.962	0.004
AST	0.991	0.974～0.996	0.010	0.985	0.974～0.996	0.006
APTT	0.949	0.830～0.981	0.006	0.902	0.830～0.981	0.015
α角	1.027	0.995～1.108	0.144	1.050	0.995～1.108	0.074

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表 4 单纯脓毒血症患者28天及90天病死率的Logistic回归分析

Table 4. Logistic regression analysis of 28-day and 90-day mortality in patients with sepsis

项目	单因素分析			多因素分析
项目	HR	95%CI	P值	HR	95%CI	P值
28天
中性粒细胞计数	0.874	0.781～0.963	<0.001	0.855	0.766～0.954	0.005
APTT	0.900	0.752～0.993	0.010	0.864	0.752～0.993	0.014
MA值	1.066	1.017～1.135	<0.001	1.053	1.026～1.165	0.006
90天
中性粒细胞计数	0.925	0.785～1.024	0.109	0.897	0.785～1.024	0.109
APTT	0.781	0.403～0.867	<0.001	0.751	0.403～0.867	0.004
MA值	1.037	1.047～1.276	<0.001	1.155	1.047～1.276	0.007

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