联合凝血功能指标在结直肠癌患者化疗后高凝状态监测中的应用价值

doi:10.19401/j.cnki.1007-3639.2024.03.005

摘要/Abstract

摘要：

背景与目的：常规凝血实验（conventional coagulation test，CCT）检测所用的血浆仅能够反映某个凝血时间点/段的单一成分，而血栓弹力图（thromboelastography，TEG）检测能够描绘凝血及纤维蛋白溶解的整体动态过程的曲线，更能独立完整地反映血液的真实状态，可作为凝血功能检测的补充。本研究旨在评估联合凝血功能指标在结直肠癌患者化疗后高凝状态监测中的应用价值，探讨结直肠癌患者化疗后血栓形成的危险因素，为临床监测高凝状态提供参考。方法：选取复旦大学附属肿瘤医院2021年6月—2023年6月收治的160例结直肠癌患者作为实验组，并选取同期的80名健康体检者作为对照组，再将实验组以是否合并血栓分为未合并血栓组（82例）和合并血栓组（78例）。研究3组对象的TEG[包括凝血反应时间（coagulation reaction time，R）、凝血形成时间（coagulation formation time，K）、血细胞凝块形成速率（blood clot formation rate，Angle）、血栓最大振幅（maximum amplitude，MA）和凝血综合指数（coagulation index，CI）]、CCT[包括活化部分凝血活酶时间（activated partial thromboplastin time，APTT）、凝血酶原时间（prothrombin time，PT）、凝血酶时间（thrombin time，TT）、纤维蛋白原（fibrinogen，Fib）、D-二聚体（D-dimer，DD）和纤维蛋白原降解产物（fibrinogen degradation products，FDP）]及血小板计数（platelet count，PLT）的差异。以是否合并血栓作为高凝状态的标准，选择其中差异有统计学意义的指标纳入二元logistic回归分析，并绘制受试者工作特征（receiver operating characteristic，ROC）曲线，分析单独及联合检测凝血功能指标对结直肠癌患者化疗后高凝状态的诊断效能。收集160例结直肠癌患者的基础信息、肿瘤分期和深静脉血栓Autar评估量表，进行logistic回归分析，探索血栓形成的危险因素。本研究经复旦大学附属肿瘤医院伦理委员会审核通过（编号：050432-4-2108*）。结果：与对照组相比，未合并血栓组的R、TT和PLT均减小（P<0.05），APTT、PT、DD和FDP均增大（P<0.05）；合并血栓组与对照组的各项指标差异均有统计学意义（P<0.05）。与未合并血栓组相比，合并血栓组的K减小（P<0.05），Angle、MA、CI、Fib、DD和FDP均增大（P<0.05）。ROC曲线分析显示，在结直肠癌患者化疗后高凝状态评估中，TEG检测的曲线下面积（area under curve，AUC）为0.756，灵敏度为67.5%，特异度为73.8%；CCT检测的AUC为0.691，灵敏度为78.8%，特异度为56.2%；联合检测的AUC为0.840，灵敏度为80.0%，特异度为77.5%。在危险因素分析中，肿瘤分期、远处转移和Autar评分与结直肠癌患者化疗后血栓的形成相关（P<0.05），3个危险因素在K、Angle、MA、CI、Fib、DD和FDP中的差异也有统计学意义（P <0.05）。结论：K、Angle、MA、CI、Fib、DD和FDP是反映高凝状态的主要指标，TEG与CCT联合检测能更好地反映结直肠癌患者化疗后的凝血状态。肿瘤分期为Ⅲ ~ Ⅳ期、有远处转移和Autar评分高可能是血栓形成的危险因素，提示可通过监测高危人群的相关凝血指标以降低血栓的发生率。

关键词: 结直肠癌, 化疗, 血栓弹力图, 常规凝血实验, 血栓

Abstract:

Background and purpose: The plasma used for routine coagulation test (CCT) can only reflect a single component at a certain coagulation time point/segment, while thromboelastography (TEG) can depict the overall dynamic process curve of coagulation and fibrinolysis, which can more independently and completely reflect the true state of the blood and can serve as a supplement to coagulation function testing. This study aimed to evaluate the application value of combined coagulation function indexes in monitoring the hypercoagulable state of patients with colorectal cancer after chemotherapy, and to explore the risk factors of thrombosis in patients with colorectal cancer after chemotherapy, so as to provide reference for clinical monitoring of hypercoagulable state. Methods: A total of 160 patients with colorectal cancer from Fudan University Shanghai Cancer Center from June 2021 to June 2023 were selected as the experimental group, and 80 healthy subjects were selected as the control group. Then the experimental group was divided into a group without thrombosis (82 cases) and a group with thrombosis (78 cases) according to whether they had thrombosis or not. The determinations of thromboelastography (TEG) [coagulation reaction time (R), coagulation formation time (K), blood clot formation rate (α-Angle), maximum amplitude (MA) and coagulation index (CI)], conventional coagulation tests (CCT) [activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fib), D-dimer (DD), fibrinogen degradation products (FDP)] and platelet count (PLT) were studied among three groups. With or without thrombosis as the criterion of hypercoagulable state, statistically significant indicators were selected to be included in the binary logistic regression analysis, and the receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic efficacy of single and combined detection of the coagulation function indicators for hypercoagulable state in patients with colorectal cancer after chemotherapy. Basic information, tumor stage and Autar score of deep vein thrombosis were collected in 160 patients with colorectal cancer. Logistic regression analysis was performed to explore the risk factors of thrombosis. This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (number: 050432-4-2108*). Results: Compared with the control group, the R, TT and PLT of the group with thrombosis were decreased (P<0.05), while APTT, PT, DD and FDP were increased (P<0.05). The differences in various indicators between the group with thrombosis and the control group were statistically significant (P<0.05). Compared with the group without thrombosis, the K in the group with thrombosis decreased (P<0.05), while Angle, MA, CI, FIB, DD and FDP all increased (P<0.05). ROC curve analysis showed that in the assessment of hypercoagulable state in patients with colorectal cancer after chemotherapy, the area under curve (AUC) of TEG was 0.756, sensitivity was 67.5%, and specificity was 73.8%. The AUC of CCT was 0.691, sensitivity was 78.8%, and specificity was 56.2%. The combined detection AUC was 0.840, sensitivity was 80.0%, and specificity was 77.5%. In the analysis of risk factors, tumor stage, distant metastasis and Autar score were correlated with thrombus formation in patients with colorectal cancer after chemotherapy (P<0.05), and the differences of the three risk factors in K, Angle, MA, CI, Fib, DD and FDP were statistically significant (P<0.05). Conclusion: K, Angle, MA, CI, Fib, DD and FDP are the main indicators to reflect the hypercoagulable state, and the combined detection of TEG and CCT can better reflect the coagulation state of patients with colorectal cancer after chemotherapy. Tumor stage Ⅲ to Ⅳ, distant metastasis and high Autar score are risk factors for thrombosis. The incidence of thrombosis can be reduced by monitoring the relevant coagulation indicators in the high-risk population.

Key words: Colorectal cancer, Chemotherapy, Thromboelastography, Conventional coagulation test, Thrombosis

中图分类号:

R735.3

陆悦, 卢仁泉, 张杰, 郑慧. 联合凝血功能指标在结直肠癌患者化疗后高凝状态监测中的应用价值[J]. 中国癌症杂志, 2024, 34(3): 278-285.

LU Yue, LU Renquan, ZHANG Jie, ZHENG Hui. Application value of combined coagulation function indicators in monitoring hypercoagulable state of patients with colorectal cancer after chemotherapy[J]. China Oncology, 2024, 34(3): 278-285.

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Group	N	R/min	K/min	Angle (deg)	MA/mm	CI	PLT/(10⁹·L^-1)
Control group	80	6.05 (4.83, 7.73)	1.85 (1.33, 2.23)	61.90 (54.55, 68.88)	57.80 (53.80, 62.70)	0.55 (-1.25, 1.90)	235.0 (166.80, 295.00)
Colorectal cancer without thrombosis group	82	5.05^a (4.15, 6.13)	1.60 (1.30, 2.18)	65.60 (60.38, 70.58)	60.60 (52.10, 64.80)	0.90 (-1.00, 2.30)	179.0^a (136.00, 250.00)
Colorectal cancer with thrombosis group	78	4.65^a (3.83, 5.50)	1.30^ab (1.00, 1.78)	70.65^ab (63.63, 75.28)	65.35^ab (60.23, 71.13)	2.20^ab (0.63, 3.18)	170.0^a (129.0, 215.3)
Group	APTT/s	PT/s	TT/s	Fib/(g·L^-1)	DD/(μg·mL^-1)	FDP/(μg·mL^-1)
Control group	28.45 (25.80, 31.93)	11.30 (9.90, 12.33)	15.30 (11.55, 16.20)	3.03 (2.40, 3.91)	0.28 (0.17, 0.43)	1.70 (0.46, 3.27)
Colorectal cancer without thrombosis group	29.35^a (27.60, 31.55)	12.05^a (11.43, 12.58)	13.80^a (12.60, 14.30)	3.07 (2.70, 3.61)	0.80^a (0.41, 1.31)	2.61^a (1.44, 4.12)
Colorectal cancer with thrombosis group	29.95^a (28.23, 31.60)	12.10^a (11.40, 12.60)	13.75^a (12.73, 14.40)	3.48^ab (2.84, 3.78)	1.27^ab (0.57, 2.05)	3.36^ab (1.78, 6.09)

Characteristic	Case N	Colorectal cancer without thrombosis group	Colorectal cancer with thrombosis group	χ²	P value
Gender				0.254	0.614
Male	87	43 (49.4)	44 (50.6)
Female	73	39 (53.4)	34 (46.6)
Age/year				1.981	0.159
<60	92	52 (56.5)	40 (43.5)
≥60	68	30 (44.1)	38 (55.9)
Basis diseases				0.434	0.933
Hypertension	23	13 (56.5)	10 (43.5)
Diabetes	15	7 (46.7)	8 (53.3)
Hyperlipidemia	15	8 (53.3)	7 (46.7)
Other	107	54 (50.5)	53 (49.5)
Stage of cancer				7.754	0.005^*
Ⅰ-Ⅱ	54	36 (66.7)	18 (33.3)
Ⅲ-Ⅳ	106	46 (43.4)	60 (56.6)
Distant metastasis				5.383	0.020^*
No	116	66 (56.9)	50 (43.1)
Yes	44	16 (36.4)	28 (63.6)
Autar score				6.293	0.043^*
Low	10	8 (80)	2 (20)
Middle	104	56 (53.8)	48 (46.2)
High	46	18 (39.1)	28 (60.9)

Group	N	K/min	Angle/deg	MA/mm	CI	Fib/(g·L^-1)	DD/(μg·mL^-1)	FDP/(μg·mL^-1)
Ⅰ-Ⅱ	54	1.50 (1.28, 2.13)	65.60 (60.53, 71.55)	60.45 (52.25, 64.93)	0.85 (-1.00, 2.65)	3.09 (2.71, 3.61)	0.68 (0.41, 1.03)	2.43 (1.23, 3.66)
Ⅲ-Ⅳ	106	1.41 (1.10, 1.80)	69.85 (62.43, 73.53)	64.65 (59.38, 70.08)	1.60 (0.15, 2.95)	3.38 (2.81, 3.72)	1.39 (0.55, 2.34)	3.61 (1.67, 6.26)
P value		0.106	0.118	0.013	0.075	0.263	<0.001	<0.001

Group	N	K/min	Angle/deg	MA/mm	CI	Fib/(g·L^-1)	DD/(μg·mL^-1)	FDP/(μg·mL^-1)
No distant metastasis	116	1.50 (1.13, 1.89)	66.00 (61.83, 71.50)	61.20 (52.40, 65.98)	0.90 (-0.55, 2.30)	3.10 (2.70, 3.65)	0.85 (0.43, 1.53)	2.56 (1.45, 4.26)
Distant metastasis	44	1.20 (1.00, 1.80)	71.50 (63.08, 75.28)	67.65 (60.78, 73.15)	2.45 (0.73, 3.48)	3.48 (2.90, 3.76)	1.47 (0.57, 2.62)	4.34 (1.89, 7.59)
P value		0.063	0.010	<0.001	<0.001	0.053	0.014	0.005

Group	N	K/min	Angle/deg	MA/mm	CI	Fib/(g·L^-1)	DD/(μg·mL^-1)	FDP/(μg·mL^-1)
Low-risk group	10	1.80 (1.40, 2.58)	65.05 (52.50, 69.83)	62.10 (51.93, 65.65)	-0.80 (-2.80, 2.30)	2.98 (2.56, 3.16)	0.49 (0.39, 0.72)	1.64 (1.24, 2.03)
Middle-risk group	104	1.50 (1.13, 1.89)	66.50 (61.83, 71.50)	60.95 (52.40, 65.98)	0.95 (-0.33, 2.38)	3.29 (2.80, 3.65)	0.98^a (0.44, 1.87)	3.18^a (1.45, 4.55)
High-risk group	46	1.20 (1.00, 1.79)	71.50^b (64.20, 75.55)	67.65^b (60.60, 72.85)	2.40^ab (0.78, 3.43)	3.48 (2.83, 3.77)	1.25^a (0.57, 2.39)	3.31^a (1.86, 6.78)