非小细胞肺癌患者凝血功能变化与肿瘤恶性程度相关性分析

doi:10.3877/cma.j.issn.1674-6902.2019.05.006

目的

探讨非小细胞肺癌凝血指标、血小板计数的变化与肿瘤病理类型、分期、淋巴结及血行转移的关系，为临床预测和判断肺癌患者病情进展和转移情况提供依据。

方法

选择2017年1月至2018年10月在本院接受治疗的99例非小细胞肺癌(NSCLC)患者作为观察组，同期体检健康人群40例作为对照组。将观察组根据患者病理类型分为鳞癌组(23例)、腺癌组(76例)，分析两组研究对象的凝血功能、D-二聚体及血小板，及临床意义，并对比分析不同临床病理类型及分期患者凝血功能的变化情况。

结果

与对照组相比，观察组PT(P<0.001)、INR(P<0.001)明显缩短，而FIB(P<0.001)、D-D(P<0.001)则明显升高；对观察组临床病理类型及分期患者分析发现，鳞癌比腺癌PT(P<0.001)、FIB(P＝0.002)、APTT(P＝0.028)、INR(P＝0.043)水平升高；与Ⅰ-Ⅲ期患者相比，Ⅳ期患者PT(P<0.001)、FIB(P<0.001)、APTT(P<0.001)升高；与N0患者相比，N1-3患者PT(P<0.001)、FIB(P<0.001)、APTT(P<0.001)升高；有无肺/胸膜外转移患者凝血指标水平差异无统计学意义(P>0.05)。临床获益组化疗后与化疗前比较，PT、INR、D-D缩短(P＝0.007，P＝0.036，P＝0.034)，TT延长(P＝0.013)。进展组化疗前后凝血指标水平差异无统计学意义。

结论

NSCLC患者凝血功能普遍存在异常，且与病理类型、肿瘤分期具有一定的相关性，肺鳞癌、分期为晚期以及存在淋巴结转移的患者更易出现高凝状态；对于临床获益组而言，化疗可以使PT、INR缩短，TT延长，增加血栓事件发生的风险。

关键词: 非小细胞肺癌, 凝血功能, 化疗, 临床意义

Objective

To analyze the relationship between the coagulation function changes and the malignancy degrees in the patients with non-small cell lung cancer (NSCLC) in order to provide bases for clinical prediction and judgment of the progress and metastasis of lung cancer patients.

Methods

In this study, 99 patients with NSCLC who were treated in our hospital from January 2017 to October 2018 were taken as a case group (the NSCLC group) and 40 healthy subjects in the same period were taken as a control group. According to the pathological type, the case group was divided into a squamous cell carcinoma group (n=23 cases) and an adenocarcinoma group (n=76 cases). A total of 50 patients had no lymph node metastasis and 49 had lymph node metastasis. Fourteen patients had no extra-lung/pleural metastasis and 13 had lung/pleural metastasis. According to the Eighth Edition of Lung Cancer TNM Staging, stage Ⅰ was found in 26 cases, stage Ⅱ in 22, stage Ⅲ in 24, and stage Ⅳ in 27. The patients with stage Ⅲ and stage Ⅳ lung cancer were divided into a clinical benefit group (n=42 cases) and a clinical progression group (n=9 cases), respectively, after two courses of conventional chemotherapy. The coagulation function, D-dimer and platelet count were detected in the two groups, and their clinical significance was analyzed. The changes of coagulation function under different clinical and pathological factors were compared and analyzed.

Results

Compared with the control group, the prothrombin time (PT, P<0.001) and the international normalized ratio (INR, P<0.001) were significantly shortened in the NSCLC group, while the fibrinogen (FIB, P<0.001) and the thrombin time (D-D, P<0.001) were significantly increased. Group analysis of the clinical and pathological factors in the patients with NSCLC found that PT (P<0.001), FIB (P=0.002), the activated partial thromboplastin time (APTT, P=0.028) and INR (P=0.043) were higher in the patients with squamous cell carcinoma than in the patients with adenocarcinoma. The levels of PT (P<0.001), FIB (P<0.001) and APTT (P<0.001) increased in stage Ⅳ patients with NSCLC compared with those of stage Ⅰ-Ⅲ patients. The levels of PT (P<0.001), FIB (P<0.001) and APTT (P<0.001) increased in N1-3 patients with NSCLC compared with those of the controls. There was no significant difference in blood coagulation indexes between the patients with or without extra-lung/pleural metastasis (P>0.05). In the clinical benefit group, PT, INR and D-D were shortened (P=0.007, P=0.036, and P=0.034, respectively) and TT increased (P=0.013) after chemotherapy compared with those before chemotherapy. There was no significant difference in the level of coagulation indexes between the clinical advanced group.

Conclusion

The coagulation function of the patients with NSCLC is generally abnormal and it has a certain correlation with the pathological type and the tumor stage. The patients with lung squamous cell carcinoma, in the advanced stage and with lymph node metastasis are more prone to hypercoagulability. PT and INR shortening and TT prolongation can be used as an early indicator of the efficacy of chemotherapy in the patients with NSCLC and can increase the occurrence of thrombotic events.

Key words: Non-small cell lung cancer, Coagulation, Chemotherapy, Clinical significance

表1 两组凝血功能相关指标的比较

凝血指标	例数	PT(s)	FiB(g/L)	TT(s)	APTT(s)	INR	D-D(mg/L)	PLT(10⁹/L)
NSCLC组	99	12.39±0.97	3.20(2.71～4.32)	17.55±1.29	34.70(28.50～39.10)	0.99(0.95～1.05)	0.60(0.38～0.87)	197.90±68.24
对照组	40	13.09±1.15	2.08(1.82～2.27)	17.75±0.97	33.00(29.03～37.83)	1.12(1.04～1.17)	0.16(0.10～0.27)	217.65±51.43
t或Z值		-3.64	-7.08	-0.89	-0.43	-6.29	-6.27	-1.31
P值		0	0	0.373	0.67	0	0	0.194

表1 两组凝血功能相关指标的比较

凝血指标	例数	PT(s)	FiB(g/L)	TT(s)	APTT(s)	INR	D-D(mg/L)	PLT(10⁹/L)
NSCLC组	99	12.39±0.97	3.20(2.71～4.32)	17.55±1.29	34.70(28.50～39.10)	0.99(0.95～1.05)	0.60(0.38～0.87)	197.90±68.24
对照组	40	13.09±1.15	2.08(1.82～2.27)	17.75±0.97	33.00(29.03～37.83)	1.12(1.04～1.17)	0.16(0.10～0.27)	217.65±51.43
t或Z值		-3.64	-7.08	-0.89	-0.43	-6.29	-6.27	-1.31
P值		0	0	0.373	0.67	0	0	0.194

表2 NSCLC患者临床病理特征与凝血功能相关指标的关系

临床病理特征		凝血指标(中位数)
临床病理特征		PT(s)	FiB(g/L)	TT(s)	APTT(s)	INR	D-D(mg/L)	PLT(10⁹/L)
病理类型
	鳞癌	13.10	4.24	17.30	37.30	1.03	0.58	185.00
	腺癌	12.20	3.09	17.45	33.20	0.98	0.62	206.00
	t或Z值	4.12	-3.11	-0.04	-2.20	-2.03	-0.46	-0.53
	P值	0.000	0.002	0.967	0.028	0.043	0.643	0.590
TNM分期
	Ⅰ	11.75	2.76	17.30	29.00	0.98	0.27	209.50
	Ⅱ	11.65	2.94	17.70	30.85	0.98	0.45	219.50
	Ⅲ	13.10	3.47	17.65	36.90	1.03	0.56	206.50
	Ⅳ	12.90	4.32	17.30	38.70	0.99	0.68	189.00
	F或χ²值	20.61	30.52	5.89	26.06	5.19	7.55	0.26
	P值	0.000	0.000	0.117	0.000	0.158	0.056	0.856
淋巴结转移
	N0	11.80	2.93	17.35	30.40	0.98	0.45	209.50
	N1～N3	12.90	3.61	17.50	37.80	1.00	0.62	193.00
	t或Z值	-5.44	-4.31	-0.20	-4.40	-1.25	-0.83	0.39
	P值	0.000	0.000	0.842	0.000	0.221	0.406	0.696
远处转移
	肺/胸膜	12.80	4.32	17.40	35.40	0.97	0.62	193.00
	肺/胸膜外	13.00	3.54	17.20	36.90	1.01	0.68	232.00
	t或Z值	-0.22	-0.62	1.21	-0.11	-0.56	-0.74	-0.94
	P值	0.826	0.538	0.234	0.913	0.574	0.460	0.345

表2 NSCLC患者临床病理特征与凝血功能相关指标的关系

临床病理特征		凝血指标(中位数)
临床病理特征		PT(s)	FiB(g/L)	TT(s)	APTT(s)	INR	D-D(mg/L)	PLT(10⁹/L)
病理类型
	鳞癌	13.10	4.24	17.30	37.30	1.03	0.58	185.00
	腺癌	12.20	3.09	17.45	33.20	0.98	0.62	206.00
	t或Z值	4.12	-3.11	-0.04	-2.20	-2.03	-0.46	-0.53
	P值	0.000	0.002	0.967	0.028	0.043	0.643	0.590
TNM分期
	Ⅰ	11.75	2.76	17.30	29.00	0.98	0.27	209.50
	Ⅱ	11.65	2.94	17.70	30.85	0.98	0.45	219.50
	Ⅲ	13.10	3.47	17.65	36.90	1.03	0.56	206.50
	Ⅳ	12.90	4.32	17.30	38.70	0.99	0.68	189.00
	F或χ²值	20.61	30.52	5.89	26.06	5.19	7.55	0.26
	P值	0.000	0.000	0.117	0.000	0.158	0.056	0.856
淋巴结转移
	N0	11.80	2.93	17.35	30.40	0.98	0.45	209.50
	N1～N3	12.90	3.61	17.50	37.80	1.00	0.62	193.00
	t或Z值	-5.44	-4.31	-0.20	-4.40	-1.25	-0.83	0.39
	P值	0.000	0.000	0.842	0.000	0.221	0.406	0.696
远处转移
	肺/胸膜	12.80	4.32	17.40	35.40	0.97	0.62	193.00
	肺/胸膜外	13.00	3.54	17.20	36.90	1.01	0.68	232.00
	t或Z值	-0.22	-0.62	1.21	-0.11	-0.56	-0.74	-0.94
	P值	0.826	0.538	0.234	0.913	0.574	0.460	0.345

表3 NSCLC临床获益组化疗前后凝血功能相关指标比较

凝血指标范围		PT(s)11-15	FIB(g/L)2-4	TT(s)14-21	APTT(s)28-44	INR0．75-1.25	D-D(mg/L)0-0.50	PLT(10⁹/L)150-350
化疗前(n＝43)		12.95(12.50～13.50)	3.70(3.15～5.01)	17.40(16.10～18.20)	37.55(34.90～40.83)	1.01(0.95～1.05)	0.61(0.42～0.81)	189.50(146.75～235.75)
化疗后(n＝43)		12.65(12.20～13.13)	3.92(3.37～4.88)	17.50(17.00～18.30)	36.45(34.08～41.23)	0.96(0.93～1.04)	0.71(0.50～1.12)	187.50(154.75～274.00)
	t或Z值	-2.69	-1.83	-2.60	-1.00	-2.10	-2.11	-1.48
	P值	0.007	0.068	0.013	0.317	0.036	0.034	0.139

表3 NSCLC临床获益组化疗前后凝血功能相关指标比较

凝血指标范围		PT(s)11-15	FIB(g/L)2-4	TT(s)14-21	APTT(s)28-44	INR0．75-1.25	D-D(mg/L)0-0.50	PLT(10⁹/L)150-350
化疗前(n＝43)		12.95(12.50～13.50)	3.70(3.15～5.01)	17.40(16.10～18.20)	37.55(34.90～40.83)	1.01(0.95～1.05)	0.61(0.42～0.81)	189.50(146.75～235.75)
化疗后(n＝43)		12.65(12.20～13.13)	3.92(3.37～4.88)	17.50(17.00～18.30)	36.45(34.08～41.23)	0.96(0.93～1.04)	0.71(0.50～1.12)	187.50(154.75～274.00)
	t或Z值	-2.69	-1.83	-2.60	-1.00	-2.10	-2.11	-1.48
	P值	0.007	0.068	0.013	0.317	0.036	0.034	0.139

表4 NSCLC临床进展组化疗前后凝血功能相关指标的比较

凝血指标范围		PT(s)11-15	FIB(g/L)2-4	TT(s)14-21	APTT(s)28-44	INR0．75-1.25	D-D(mg/L)0-0.50	PLT(10⁹/L)150-350
化疗前(n＝9)		12.67±1.14	4.29±1.55	17.24±1.19	34.82±7.26	1.04±0.08	1.54±1.41	233.33±59.20
化疗后(n＝9)		12.87±0.93	4.05±0.82	17.88±1.40	38.22±5.36	0.98±0.11	1.48±1.70	239.44±87.35
	t值	-0.62	0.62	-1.27	-1.33	1.54	0.12	-0.22
	P值	0.554	0.554	0.240	0.219	0.162	0.908	0.831

表4 NSCLC临床进展组化疗前后凝血功能相关指标的比较

凝血指标范围		PT(s)11-15	FIB(g/L)2-4	TT(s)14-21	APTT(s)28-44	INR0．75-1.25	D-D(mg/L)0-0.50	PLT(10⁹/L)150-350
化疗前(n＝9)		12.67±1.14	4.29±1.55	17.24±1.19	34.82±7.26	1.04±0.08	1.54±1.41	233.33±59.20
化疗后(n＝9)		12.87±0.93	4.05±0.82	17.88±1.40	38.22±5.36	0.98±0.11	1.48±1.70	239.44±87.35
	t值	-0.62	0.62	-1.27	-1.33	1.54	0.12	-0.22
	P值	0.554	0.554	0.240	0.219	0.162	0.908	0.831

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Relevance analysis of coagulation function changes and malignancy degrees in patients with non-small cell lung cancer

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Relevance analysis of coagulation function changes and malignancy degrees in patients with non-small cell lung cancer