中国118例颅内静脉窦血栓患者的临床特点及危险因素分析

doi:10.16150/j.1671-2870.2023.03.09

摘要/Abstract

摘要：

目的：分析中国颅内静脉窦血栓（cerebral venous sinus thrombosis，CVST）患者的临床特征和血栓危险因素，为该疾病的防治提供参考。方法：纳入2015年1月至2022年12月就诊于上海交通大学医学院附属瑞金医院血栓与止血门诊的118例CVST患者，患者均经2种以上的影像学检查确诊。收集其临床资料，结合实验室检查及易栓症基因Panel筛查结果，采用单因素和多因素Logistic回归分析，探讨CVST患者发生血栓的独立危险因素。结果：118例CVST患者中，88.1%（104/118）的患者初发CVST年龄<45岁。57.6%（68/118）的患者仅经历1次CVST，33.1%（39/118）的患者发生至少2次静脉血栓，37.3%（44/118）的患者除CVST外，还经历了下肢深静脉血栓、肺栓塞等其他部位血栓。CVST累及的各个静脉窦中，上矢状窦最易形成血栓（77/118），有54.2％（64/118）的患者存在多部位静脉窦同时受累。易栓症危险因素筛查显示，70.3%（83/118）的患者至少携带一个较明确的血栓危险因素，遗传性和获得性危险因素的检出率分别为63/118（53.3%）和38/118（32.2%）。男性患者的危险因素主要为抗凝蛋白缺陷症（35/66）和抗磷脂综合征（5/66）等，女性患者则以抗凝蛋白缺陷症（20/52）、产科因素（11/47）及服用避孕药（5/47）等为主。血栓危险因素不明的35例患者中，仍有超过30%的患者曾经历反复血栓或其他部位静脉血栓。单因素和多因素Logistic回归分析显示，携带遗传性危险因素[危险度（odds ratio, OR）=21.643，95％置信区间（confidence interval, CI）为9.455~49.544，P<0.000 1]和获得性危险因素（OR=10.836，95%CI为4.306~27.270，P<0.000 1）均为CVST发生的独立危险因素。携带遗传性危险因素（OR=2.270，95%CI为1.021~5.048，P=0.044）也是CVST患者反复发生血栓的独立危险因素。结论：在中国人群中，CVST好发于中青年期，70.3%的患者至少携带一个较明确的血栓危险因素，其中遗传性危险因素是CVST的主要病因，检出率达53.3%，明显高于国外报道（遗传性危险因素检出率22%）。携带遗传性危险因素的患者，发生CVST或反复静脉血栓的风险显著升高，针对CVST高风险人群应做到早预防、早诊断、早治疗。

关键词: 颅内静脉窦血栓, 临床特征, 遗传性危险因素, 获得性危险因素

Abstract:

Objective: To analyze the clinical characteristics and thrombotic risk factors of cerebral venous sinus thrombosis (CVST) in Chinese population, in order to provide reference for the clinical diagnosis, prevention and treatment of CVST. Methods: A total of 118 CVST patients who visited the Thrombosis and Hemostasis Clinic of Ruijin Hospital from January in 2015 to December in 2022 were enrolled. The clinical data, imaging characteristics, and thrombotic gene panel were collected, and independent risk factors for thrombosis, recurrence, and multi-site thrombosis in CVST patients were studied through univariate and multivariate logistic regression. Results: Among 118 CVST patients, 88.1% (104/118) patients firstly developed CVST at age younger than 45 years old.It revealed that 57.6% patients (68/118) only suffered CVST once,and 33.1% patients (39/118) experienced thrombotic events at least twice, while 37.3% patients (44/118) suffered multi-site venous thromboembolism (VTE). The superior sagittal sinus was the most common venous sinus to form thrombosis (77/118), and multi-sites of venous sinus were involved simultaneously in 54.2% patients (64/118). The risk factor screening for thrombophilia showed that 70.3% patients (83/118) carried at least one thrombotic risk factor, including 53.3% patients (63/118) with inherited risk factors and 32.2% patients (38/118) with acquired risk factors. The main risk factors for males were anticoagulant protein deficiency (35/66) and antiphospholipid syndrome (5/66), while the risk factors for females mainly included anticoagulant protein deficiency (20/52), pregnancy/postpartum period (11/47), and contraceptive use (5/47). Among 35 patients with unknown risk factors, more than 30% of them experienced recurrent or multi-site thrombosis, and the underlying etiology in these patients still need to be further investigated. Univariate and multivariate logistic regression analysis showed that both inherited risk factors (odds ratio, OR=21.643, 95% confidence interval， CI 9.455-49.544, P<0.0001) and acquired risk factors (OR=10.836, 95% CI 4.306-27.270, P<0.0001) were independent risk factors for the occurrence of CVST. Genetic risk factor (OR=2.270, 95% CI 1.021-5.048, P=0.044) was an independent risk factor for recurrent thrombosis in CVST patients. Conclusions: In Chinese population, CVST is more common in middle-aged and young populations.，with 70.3% patients carrying at least one thrombotic risk factor. Genetic risk factors are the main cause of CVST in China and the detectable rate is 53.3%, which is significantly higher than that (22%) reported abroad. The patients with genetic risk factors have a significantly increased risk of developing CVST or recurrent thrombosis. Identification of thrombotic risk factors, prevention, diagnosis and treatment should be carried out earlier for individuals with high-risk CVST.

Key words: Cerebral venous sinus thrombosis, Clinical features, Genetic risk factors, Acquired risk factors

中图分类号:

R743.32

李蕾, 吴希, 戴菁, 武文漫, 丁秋兰, 王学锋. 中国118例颅内静脉窦血栓患者的临床特点及危险因素分析[J]. 诊断学理论与实践, 2023, 22(03): 261-269.

LI Lei, WU Xi, DAI Jing, WU Wenman, DING Qiulan, WANG Xuefeng. Clinical characteristics and risk factor analysis of 118 patients with cerebral venous sinus thrombosis[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(03): 261-269.

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Parameter	CVST patients (N=118)	Controls (N=149)	P value
Age（y）
Age at first referral to the center	34.42±11.75	32.89±7.42	0.195 9
Age at first onset of CVST	32.59±12.06	NA	-
Gender
Male	66 (55.9%)	82 (55.0%)	0.883 4
Female	52 (44.1%)	67 (45.0%)
VTE occurrences
1	79 (66.9%)	NA	-
≥2	39 (33.1%)	NA	-
History of VTE
CVST	74 (62.7%)	NA	-
CVST+DVT/PE/PVT	44 (37.3%)	NA	-
Occluded sinus/vein
Superior sagittal sinus	77 (65.3%)	NA	-
Transverse sinus	70 (60.0%)	NA	-
Sigmoid sinus	50 (42.3%)	NA	-
Straight sinus	7 (5.9%)	NA	-

Parameter	CVST patients (N=118)	Controls (N=149)	P value
Genetic risk factors	63 (53.4)	8 (5.4)	<0.000 1
AT deficiency	12 (10.2)	0	-
PC deficiency	22 (18.6)	6 (4.0)	0.000 1
PS deficiency	16 (13.6)	1 (0.7)	<0.000 1
PS&PC deficiency	3 (2.5)	0	-
AT&PC deficiency	2 (1.7)	0	-
Other thrombotic mutations	8 (6.8)	1 (0.7)	0.016 2
Acquired risk factors	38 (32.2)	7 (4.7)	<0.000 1
Pregnancy/puerperium ^b)	11 (24.4)	1 (1.5)	0.000 5
Oral contraceptive use^b)	5 (11.1)	3 (4.5)	0.347 5
Antiphospholipid syndrome	6 (5.1)	0	-
Thrombocytosis	5 (4.2)	0	-
Major surgery	4 (3.4)	0	-
Malignancy	1 (0.8)	0	-
Systemic lupus erythematosus	1 (0.8)	0	-
Hyperthyroidism	1 (0.8)	0	-
Anemia	1 (0.8)	1 (0.7)	0.583 2
Hyperhomocysteinemia	1 (0.8)	1 (0.7)	0.583 2
Intracranial hypotension	1 (0.8)	0	-
Long-range flight	1 (0.8)	0	-
Immobilization	1 (0.8)	1 (0.7)	0.583 2
None identified	35 (29.7)	135 (90.6)	<0.000 1

Parameter	Only with genetic VTE risk factors (group 1)	Only with acquired VTE risk factors (group 2)	With both genetic and acquired VTE risk factors (group 3)	Without significant VTE risk factors (group 4)
Number (%)	45 (38.1)	20 (16.9)	18 (15.3)	35 (29.7)
First-onset age of CVST	32.53±13.02	34.75±10.65	30.11±8.76	32.71±12.56
Gender
Male	31 (68.9)	4 (20.0)	6 (33.3)	25 (71.4)
Female	14 (31.1)	16 (80.0)	12 (66.7)	10 (28.6)
Number of VTE occurrences
1	28 (62.2)	18 (90.0)	9 (50.0)	24 (68.6)
≥2	17 (37.8)	2 (10.0)	9 (50.0)	11 (31.4)
Location of VTE
CVST	28 (62.2)	15 (75.0)	10 (55.6)	23 (65.7)
CVST+DVT/PE/PVT	17 (37.8)	5 (25.0)	8 (44.4)	12 (34.3)
Occluded sinus/vein
Superior sagittal sinus	31 (68.8)	10 (50.0)	12 (66.7)	24 (68.6)
Transverse sinus	27 (60.0)	10 (50.0)	12 (66.7)	21 (60.0)
Sigmoid sinus	23 (51.1)	8 (40.0)	7 (38.9)	12 (34.3)
Straight sinus	2 (4.4)	1 (5.0)	1 (5.6)	3 (8.6)
VTE history
Positive	14 (31.1)	1 (5.0)	4 (22.2)	2 (5.7)
Negative	31 (68.9)	19 (95.0)	14 (77.8)	33 (94.3)

Variants	Univariate analysis		Multivariate analysis
Variants	Adjusted OR (95%CI)	P value	Adjusted OR (95%CI)	P value
Age^a)	0.997 (0.972-1.022)	0.807 0	0.994 (0.962-1.027)	0.706 0
Gender
Male vs. Female	1.037 (0.638-1.686)	0.883 0	1.456 (0.756-2.804)	0.261 0
With genetic risk factors
Yes vs. No	20.189 (9.081-44.881)	<0.000 1	21.643 (9.455-49.544)	<0.000 1
With acquired risk factors
Yes vs. No	9.636 (4.113-22.577)	<0.000 1	10.836 (4.306-27.270)	<0.000 1

Variants	Recurrent VTE		Multi-site VTE
Variants	Adjusted OR (95%CI)	P value	Adjusted OR (95%CI)	P value
Univariate analysis
Onset age of CVST	0.986 (0.954-1.019)	0.388	1.013 (0.982-1.045)	0.412
Gender
Male vs. Female	2.158 (0.971-4.797)	0.059	1.588 (0.744-3.392)	0.232
With genetic risk factors
Yes vs. No	2.270 (1.021-5.048)	0.044	1.676 (0.785-3.581)	0.182
With acquired risk factors
Yes vs. No	0.757 (0.327-1.749)	0.514	1.147 (0.518-2.538)	0.735
Family history of VTE
Yes vs. No	1.016 (0.373-2.764)	0.976	0.621 (0.222-1.741)	0.365
Multivariate analysis
Onset age of CVST	0.991 (0.958-1.025)	0.595	1.017 (0.986-1.050)	0.285
Gender
Male vs. Female	2.166 (0.961-4.883)	0.062	1.613 (0.745-3.493)	0.225
With genetic risk factors
Yes vs. No	2.278 (1.012-5.129)	0.047	1.676 (0.785-3.581)	0.182
With acquired risk factors
Yes vs. No	1.087 (0.423-2.797)	0.862	1.555 (0.630-3.841)	0.338
Family history of VTE
Yes vs. No	0.693 (0.235-2.043)	0.507	0.474 (0.160-1.402)	0.177