成年严重烧伤患者早期凝血特征的多中心回顾分析及预后的危险因素分析

沈拓; 马琪敏; 褚志刚; 张逸; 汤文彬; 崔培; 李晓亮; 常刘; 陈昭宏; 常菲; 刘永计; 吴抽浪; 郭光华; 朱峰

doi:10.3760/cma.j.cn501225-20250530-00250

成年严重烧伤患者早期凝血特征的多中心回顾分析及预后的危险因素分析

doi: 10.3760/cma.j.cn501225-20250530-00250

沈拓^{1, 2},
马琪敏¹,
褚志刚³,
张逸⁴,
汤文彬⁵,
崔培⁶,
李晓亮⁷,
常刘⁸,
陈昭宏⁹,
常菲¹⁰,
刘永计¹¹,
吴抽浪¹²,
郭光华¹³,
朱峰^2, ,

1.
同济大学附属东方医院重症医学科,上海　　200120
2.
海军军医大学第一附属医院烧创伤与创面修复科,上海　　200433
3.
武汉大学附属同仁医院暨武汉市第三医院烧伤科,武汉　　430060
4.
南通大学附属医院烧伤整形科创面修复科,南通　　226001
5.
暨南大学附属广州红十字会医院烧伤整形科,广州　　510220
6.
解放军第924医院烧伤整形科,桂林　　541002
7.
郑州市第一人民医院烧伤科,郑州　　450004
8.
大连市第四人民医院烧伤整形科,大连　　116031
9.
福建医科大学附属协和医院烧伤与创面修复科,福州　　350001
10.
张家港市第一人民医院烧伤整形科,张家港　　215600
11.
黑龙江省医院烧伤科,哈尔滨　　150036
12.
浙江省台州医院烧伤科,临海　　317000
13.
南昌大学第一附属医院烧伤整形与创面修复医学中心,南昌　　330006

基金项目:

国家重点研发计划 2024YFC3505700

国家重点研发计划“干细胞及转化研究”重点专项 2019YFA0110601

详细信息

通讯作者:
朱峰,Email：alexzhujunchi@hotmail.com

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出版历程
- 收稿日期: 2025-05-30

Multicenter retrospective analysis of early coagulation characteristics and risk factors for prognosis of adult patients with severe burns

Shen Tuo^{1, 2},
Ma Qimin¹,
Chu Zhigang³,
Zhang Yi⁴,
Tang Wenbin⁵,
Cui Pei⁶,
Li Xiaoliang⁷,
Chang Liu⁸,
Chen Zhaohong⁹,
Chang Fei¹⁰,
Liu Yongji¹¹,
Wu Choulang¹²,
Guo Guanghua¹³,
Zhu Feng^{2
, ,}

1.
Department of Critical Care Medicine, Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, China
2.
Department of Burn Trauma and Wound Repair, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
3.
Department of Burns, Tongren Hospital of Wuhan University ＆ Wuhan Third Hospital, Wuhan 430060, China
4.
Department of Burns and Plastic Surgery, Wound Repair, Affiliated Hospital of Nantong University, Nantong 226001, China
5.
Department of Burns and Plastic Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou 510220, China
6.
Department of Burns and Plastic Surgery, the 924th Hospital of PLA, Guilin 541002, China
7.
Department of Burns, Zhengzhou First People's Hospital, Zhengzhou 450004, China
8.
Department of Burns and Plastic Surgery, the Fourth People's Hospital of Dalian, Dalian 116031, China
9.
Department of Burns and Wound Repair, Fujian Medical University Union Hospital, Fuzhou 350001, China
10.
Department of Burns and Plastic Surgery, Zhangjiagang First People′s Hospital, Zhangjiagang 215600, China
11.
Department of Burns, Heilongjiang Provincial Hospital, Harbin 150036, China
12.
Department of Burns, Taizhou Hospital of Zhejiang Province, Linhai 317000, China
13.
Medical Center of Burn Plastic and Wound Repair, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China

Funds:

National Key R&D Program of China 2024YFC3505700

National Key R&D Program "Stem Cell and Transformation Research" Key Special Project 2019YFA0110601

More Information

Corresponding author: Zhu Feng, Email: alexzhujunchi@hotmail.com

摘要

摘要: 目的探讨成年严重烧伤患者早期凝血特征及预后的危险因素。方法该研究为回顾性病例系列研究。2015年1月—2020年12月,全国12家医院共收治583例符合入选标准的成年严重烧伤患者,其中海军军医大学第一附属医院75例、武汉大学附属同仁医院暨武汉市第三医院64例、南通大学附属医院48例、暨南大学附属广州红十字会医院146例、解放军第924医院55例、郑州市第一人民医院46例、大连市第四人民医院35例、福建医科大学附属协和医院20例、张家港市第一人民医院18例、黑龙江省医院7例、浙江省台州医院18例、南昌大学第一附属医院51例。统计患者总体临床特征和伤后24 h内凝血功能指标,前者包括性别、年龄、烧伤总面积、吸入性损伤程度、致伤原因,后者包括凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、国际标准化比值（INR）及D-二聚体、纤维蛋白原（FIB）、血小板计数（PLT）和血清总钙水平。根据前述指标的相关数据,计算患者脓毒症相关性器官功能衰竭评价（SOFA）评分、改良Baux评分和简明烧伤严重指数（ABSI）评分。按照伤后28 d内的存活结局,将患者分为存活组（499例）和死亡组（84例）。比较2组患者总体临床特征指标及凝血功能指标。按照烧伤的严重程度,将患者分为烧伤总面积<50%体表总面积（TBSA）的重度烧伤组（185例）、烧伤总面积≥50%TBSA且<80%TBSA的特重烧伤组（251例）和烧伤总面积≥80%TBSA的危重烧伤组（147例）,比较3组患者凝血功能指标。按照烧伤早期入院的具体时间,将伤后<2 h、≥2 h且<4 h、≥4 h且<8 h、≥8 h且<16 h及≥16 h且<24 h入院的患者分别设为烧伤早期₁组（207例）、烧伤早期₂组（158例）、烧伤早期₃组（129例）、烧伤早期₄组（54例）、烧伤早期₅组（35例）,比较5组患者凝血功能指标。筛选影响583例成年严重烧伤患者伤后28 d死亡的独立危险因素。根据独立危险因素绘制预测模型列线图。绘制基于SOFA评分、ABSI评分、改良Baux评分的预测模型的受试者操作特征（ROC）曲线并计算曲线下面积（AUC）,并与基于列线图评分的预测模型的AUC进行比较。评估前述各预测模型的效能。结果 583例患者中男409例、女174例,年龄18~97岁,烧伤总面积60.00%（44.50%,80.00%）TBSA,中重度吸入性损伤者138例。与存活组比较,死亡组患者年龄、烧伤总面积、INR更大,PT、APTT更长,D-二聚体、PLT水平及中重度吸入性损伤患者占比更高（Z值分别为6.47、7.48、3.48、2.89、2.79、5.33、2.59,χ²=11.30,P值均<0.05）；2组患者仅D-二聚体水平高于正常范围的上限。重度烧伤组、特重烧伤组、危重烧伤组患者PT、APTT、INR及D-二聚体、PLT、血清总钙水平组间总体比较,差异均有统计学意义（H值分别为17.85、19.78、26.89、52.64、14.21、12.90,P<0.05）。烧伤早期₁组、烧伤早期₂组、烧伤早期₃组、烧伤早期₄组、烧伤早期₅组患者PT、APTT、INR及D-二聚体、FIB、PLT及血清总钙水平组间总体比较,差异均有统计学意义（H值分别为29.66、60.13、25.51、28.24、14.38、11.41、42.96,P<0.05）。多因素logistic回归分析显示,年龄、烧伤总面积、APTT及D-二聚体水平均为成年严重烧伤患者伤后28 d死亡的独立危险因素（比值比分别为1.056、1.048、1.029、1.018,95%置信区间分别为1.036~1.076、1.033~1.063、1.005~1.053、1.002~1.035,P<0.05）。ROC曲线显示,基于SOFA评分、ABSI评分和改良Baux评分的预测模型的AUC分别为0.66、0.76、0.80,95%置信区间分别为0.61~0.75、0.71~0.82、0.74~0.86,均低于基于列线图评分的预测模型的0.81（95%置信区间为0.76~0.87）。DeLong检验显示,基于列线图评分的预测模型对成年严重烧伤患者伤后28 d死亡风险的预测能力明显优于基于SOFA评分和ABSI评分的预测模型（P值均<0.05）,而与基于改良Baux评分的预测模型相近（P>0.05）。结论成年严重烧伤患者早期仅D-二聚体水平高于正常范围的上限。年龄、烧伤总面积、APTT与D-二聚体水平均为成年严重烧伤患者伤后28 d死亡的独立危险因素。
- 烧伤 /
- 成年人 /
- 预后 /
- 危险因素 /
- 凝血 /
- 回顾性研究
Abstract: Objective To investigate the early coagulation characteristics and risk factors for prognosis of adult patients with severe burns. Methods This study was a retrospective study of case series. A total of 583 adult patients with severe burns who met the inclusion criteria were admitted to the 12 hospitals in China from January 2015 to December 2020, including 75 cases from the First Affiliated Hospital of Naval Medical University, 64 cases from Tongren Hospital of Wuhan University ＆ Wuhan Third Hospital, 48 cases from the Affiliated Hospital of Nantong University, 146 cases from the Guangzhou Red Cross Hospital of Jinan University, 55 cases from the 924^th Hospital of PLA, 46 cases from Zhengzhou First People's Hospital, 35 cases from the Fourth People's Hospital of Dalian, 20 cases from Fujian Medical University Union Hospital, 18 cases from Zhangjiagang First People's Hospital, 7 cases from Heilongjiang Provincial Hospital, 18 cases from Taizhou Hospital of Zhejiang Province, and 51 cases from the First Affiliated Hospital of Nanchang University. The general clinical characteristics (including gender, age, total burn area, degree of inhalation injury, and cause of burn) and coagulation function indicators within 24 hours after injury (including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), and D-dimer, fibrinogen (FIB), platelets (PLT), and serum total calcium levels) of patients were statistically analyzed. Based on the data of the above indicators, the sepsis-related organ failure assessment (SOFA) score, modified Baux score, and abbreviated burn severity index (ABSI) score of patients were calculated. According to the survival outcome within 28 days after injury, the patients were divided into survival group (499 cases) and death group (84 cases). General clinical characteristics and coagulation function indicators were compared between the 2 groups of patients. According to the severity of burns, patients were divided into three groups: severe burn group (185 cases ) with a total burn area <50% total body surface area (TBSA), extremely severe burn group (251 cases) with a total burn area ≥50% and <80%TBSA, and critical burn group (147 cases) with a total burn area ≥80%TBSA. Coagulation function indicators were compared among the 3 groups of patients. Based on the specific time of admission at the early stage of burns, patients with admission time <2 h, ≥2 h and <4 h, ≥4 h and <8 h, ≥8 h and <16 h, and ≥16 h and <24 h after burns were divided respectively into early burn group 1 (207 cases), early burn group 2 (158 cases), early burn group 3 (129 cases), early burn group 4 (54 cases), and early burn group 5 (35 cases), and the coagulation function indicators were compared among the 5 groups of patients. The independent risk factors affecting mortality 28 days after injury in 583 adult patients with severe burns were screened. A predictive nomogram was constructed based on the independent risk factors. Receiver operating characteristic (ROC) curves were constructed and the area under the curves (AUCs) was calculated for prediction models based on SOFA score, ABSI score, and modified Baux score. The AUC based on the nomogram score was compared with those of the aforementioned prediction models. The efficacy of the aforementioned prediction models was assessed. Results Among the 583 patients, there were 409 males and 174 females, aged 18-97 years, with total burn area of 60.00% (44.50%, 80.00%) TBSA and 138 patients with moderate-to-severe inhalation injury. Compared with those in survival group, patients in death group had larger age, total burn area, and INR, longer PT and APTT, higher D-dimer and PLT levels, and proportion of moderate-to-severe inhalation injury (with Z values of 6.47, 7.48, 3.48, 2.89, 2.79, 5.33, and 2.59, respectively, χ²=11.30, all P values<0.05). Only D-dimer level in the 2 group of patients was above the upper limit of the normal range. There were statistically significant differences among severe burn group, extremely severe burn group, and critical burn group of patients in terms of PT, APTT, INR, and D-dimer, PLT, serum total calcium levels (with H values of 17.85, 19.78, 26.89, 52.64, 14.21, and 12.90, respectively, P<0.05). There were statistically significant differences among early burn group 1, early burn group 2, early burn group 3, early burn group 4, and early burn group 5 of patients in terms of PT, APTT, INR, and D-dimer, FIB, PLT, serum total calcium levels (with H values of 29.66, 60.13, 25.51, 28.24, 14.38, 11.41, and 42.96, respectively, P<0.05). Multivariate logistic regression analysis showed that age, total burn area, APTT, and D-dimer level were independent risk factors for mortality 28 days after injury in adult patients with severe burns (with odds ratios of 1.056, 1.048, 1.029, and 1.018, respectively, 95% cofidence intervals (CIs) of 1.036-1.076, 1.033-1.063, 1.005-1.053, and 1.002-1.035, respectively, P<0.05). The ROC curves showed that the AUCs of the predictive models based on the SOFA score, ABSI score, and modified Baux score were 0.66, 0.76, and 0.80, respectively, with 95% CIs of 0.61-0.75, 0.71-0.82, and 0.74-0.86, respectively, which were all lower than 0.81 (95% CI of 0.76-0.87) of the nomogram score-based predictive model. The DeLong test showed that the predictive ability of the nomogram score-based model for predicting mortality risk in adult patients with severe burns 28 days after injury was significantly better than those of the models based on the SOFA score and ABSI score (both P values<0.05), but similar to that of the prediction model based on the modified Baux score (P>0.05). Conclusions In the early stage of adult patients with severe burns, only D-dimer level was above the upper limit of the normal range. Age, total burn area, APTT, and D-dimer level are all independent risk factors for mortality in adult patients with severe burns 28 days after injury.
- Burns /
- Adult /
- Prognosis /
- Risk factors /
- Coagulation /
- Retrospective study
沈拓：提出研究主题,设计论文框架,采集、分析并解释数据,起草并修改文章；马琪敏、褚志刚、张逸、汤文彬、崔培、李晓亮、常刘：采集、分析数据,指导写作；陈昭宏、常菲、刘永计、吴抽浪、郭光华：采集、分析数据,研究指导,对文章内容进行批判性审阅；朱峰：研究指导,论文审阅及修改,经费支持

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图 1 583例成年严重烧伤患者伤后28 d死亡风险的列线图预测模型

注：TBSA为体表总面积,APTT为活化部分凝血活酶时间

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图 2 583例成年严重烧伤患者伤后28 d死亡风险的列线图预测能力评估

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图 3 基于不同评分的预测模型预测583例成年严重烧伤患者伤后28 d死亡风险能力比较

注：图中直线为参考线；列线图指基于年龄、烧伤总面积、活化部分凝血活酶时间及D-二聚体水平构建的预测模型；SOFA为脓毒症相关性器官功能衰竭评价,ABSI为简明烧伤严重指数

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Table 1. 2组成年严重烧伤患者总体临床特征比较

组别	例数	性别（例）		年龄[岁,M（Q₁,Q₃）]	烧伤总面积[%TBSA,M（Q₁,Q₃）]	致伤原因（例）				吸入性损伤程度（例）
组别	例数	男	女	年龄[岁,M（Q₁,Q₃）]	烧伤总面积[%TBSA,M（Q₁,Q₃）]	火焰烧伤	化学烧伤	电烧伤	热液烫伤	轻度或无	中重度
存活组	499	347	152	47.00（35.00,56.00）	55.00（40.00,75.00）	406	18	25	50	393	106
死亡组	84	62	22	56.00（47.75,68.00）	85.00（60.00,94.25）	73	1	1	9	52	32
统计量值		χ² =0.44		Z=6.47	Z=7.48	—				χ²=11.30
P值		0.508		<0.001	<0.001	0.268				<0.001
注：TBSA为体表总面积；按照伤后28 d内的存活结局,将患者分为存活组和死亡组；“—”表示无此项

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Table 2. 2组成年严重烧伤患者凝血功能指标比较[M（Q₁,Q₃）]

组别	例数	PT（s）	APTT（s）	TT（s）	D-二聚体（mg/L）	INR	FIB（g/L）	PLT（×10⁹/L）	血清总钙（mmol/L）
存活组	499	11.60（11.00,12.60）	27.10（23.35,31.65）	18.50（16.90,20.10）	2.27（1.05,5.27）	0.99（0.93,1.08）	2.50（2.00,3.12）	234.00（171.50,303.50）	2.04（1.82,2.19）
死亡组	84	12.20（11.25,14.00）	31.30（24.43,38.20）	18.60（16.88,20.33）	5.32（2.63,14.96）	1.06（0.97,1.19）	2.58（1.96,3.34）	267.50（197.75,363.50）	2.01（1.83,2.16）
Z值		2.89	2.79	0.50	5.33	3.48	0.47	2.59	0.24
P值		0.004	0.005	0.614	<0.001	0.001	0.639	0.010	0.813
注：PT为凝血酶原时间,APTT为活化部分凝血活酶时间,TT为凝血酶时间,INR为国际标准化比值,FIB为纤维蛋白原,PLT为血小板计数；按照伤后28 d内的存活结局,将患者分为存活组和死亡组

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Table 3. 3组成年严重烧伤患者凝血功能指标比较[M（Q₁,Q₃）]

组别	例数	PT（s）	APTT（s）	TT（s）	D-二聚体（mg/L）	INR	FIB（g/L）	PLT（×10⁹/L）	血清总钙（mmol/L）
重度烧伤组	185	11.50（10.80,12.10）	25.90（23.10,29.20）	18.50（17.00,19.70）	1.60（0.70,3.70）	0.98（0.91,1.04）	2.60（2.00,3.10）	223.00（175.00,273.00）	2.08（1.87,2.20）
特重烧伤组	251	11.70（11.10,12.75）	27.90（23.55,32.85）	18.00（16.40,19.95）	2.59（1.20,6.20）	1.00（0.94,1.10）	2.51（2.00,3.26）	238.00（168.00,309.50）	2.03（1.87,2.17）
危重烧伤组	147	12.00（11.20,13.80）	29.60（23.90,37.45）	19.40（17.70,21.25）	4.70（2.07,7.42）	1.05（0.96,1.16）	2.43（1.86,3.12）	270.00（200.50,362.00）	1.96（1.67,2.14）
H值		17.85	19.78	20.83	52.64	26.89	1.71	14.21	12.90
P值		<0.001	<0.001	0.614	<0.001	<0.001	0.424	0.001	0.002
注：PT为凝血酶原时间,APTT为活化部分凝血活酶时间,TT为凝血酶时间,INR为国际标准化比值,FIB为纤维蛋白原,PLT为血小板计数；按照烧伤的严重程度,将患者分为烧伤总面积<50%体表总面积（TBSA）的重度烧伤组、烧伤总面积≥50%TBSA且<80%TBSA的特重烧伤组和烧伤总面积≥80%TBSA的危重烧伤组

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Table 4. 5组成年严重烧伤患者凝血功能指标比较[M（Q₁,Q₃）]

组别	例数	PT（s）	APTT（s）	TT（s）	D-二聚体（mg/L）	INR	FIB（g/L）	PLT（×10⁹/L）	血清总钙（mmol/L）
烧伤早期₁组	207	11.50（10.80,12.30）	25.10（22.10,29.90）	18.60（17.00,20.20）	1.65（0.76,4.49）	0.98（0.93,1.05）	2.57（2.00,3.22）	248.00（189.50,324.00）	2.11（1.96,2.24）
烧伤早期₂组	158	11.65（11.00,12.67）	26.60（23.50,30.60）	18.30（16.90,20.20）	3.02（1.45,7.39）	1.00（0.93,1.10）	2.40（1.89,3.06）	245.50（171.75,320.25）	2.05（1.86,2.19）
烧伤早期₃组	129	11.80（11.20,13.00）	29.00（24.50,33.00）	18.80（17.30,20.50）	3.22（1.23,6.61）	1.00（0.96,1.12）	2.46（2.00,3.12）	237.00（180.00,297.00）	1.97（1.73,2.11）
烧伤早期₄组	54	12.65（11.72,14.50）	33.75（28.92,42.03）	17.85（16.50,19.80）	3.06（1.83,6.69）	1.08（1.01,1.24）	2.44（1.65,3.09）	220.50（168.00,279.50）	1.88（1.66,2.06）
烧伤早期₅组	35	11.70（10.90,12.75）	29.60（25.00,35.80）	17.30（15.70,19.40）	1.87（0.98,3.92）	1.00（0.92,1.10）	2.94（2.58,3.80）	195.00（122.00,251.00）	1.86（1.30,2.02）
H值		29.66	60.13	7.68	28.24	25.51	14.38	11.41	42.96
P值		<0.001	<0.001	0.104	<0.001	<0.001	0.006	0.022	<0.001
注：PT为凝血酶原时间,APTT为活化部分凝血活酶时间,TT为凝血酶时间,INR为国际标准化比值,FIB为纤维蛋白原,PLT为血小板计数；按照烧伤早期入院的具体时间,将伤后<2 h、≥2 h且<4 h、≥4 h且<8 h、≥8 h且<16 h及≥16 h且<24 h入院的患者分别设为烧伤早期₁组、烧伤早期₂组、烧伤早期₃组、烧伤早期₄组、烧伤早期₅组

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Table 5. 影响583例成年严重烧伤患者伤后28 d死亡的单因素logistic回归分析结果

自变量	比值比	95%置信区间	P值
年龄（岁）	1.039	1.025~1.053	<0.001
烧伤总面积（%TBSA）	1.048	1.033~1.063	<0.001
中重度吸入性损伤	1.604	1.326~1.941	<0.001
PT（s）	1.193	1.084~1.319	<0.001
APTT（s）	1.059	1.041~1.077	<0.001
D-二聚体（mg/L）	1.021	1.009~1.034	<0.001
INR	6.056	2.144~17.392	0.001
PLT（×10⁹/L）	1.002	1.001~1.004	0.002
注：TBSA为体表总面积,PT为凝血酶原时间,APTT为活化部分凝血活酶时间,INR为国际标准化比值,PLT为血小板计数

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Table 6. 影响583例成年严重烧伤患者伤后28 d死亡的多因素logistic回归分析结果

自变量	比值比	95%置信区间	P值
年龄（岁）	1.056	1.036~1.076	<0.001
烧伤总面积（%TBSA）	1.048	1.033~1.063	<0.001
APTT（s）	1.029	1.005~1.053	0.017
D-二聚体（mg/L）	1.018	1.002~1.035	0.027
注：TBSA为体表总面积,APTT为活化部分凝血活酶时间