目的:通过分析108例静脉血栓栓塞症(VTE)患者的临床资料,检查患者蛋白C (PC)、蛋白S (PS)、抗凝血酶III (ATIII)活性水平,探讨原发性和继发性危险因素与静脉血栓栓塞症的关系,为VTE的及早预防提供理论依据。方法:收集克拉玛依市中心医院108例VTE病例组(2014年1月至2019年1月收治的VTE)及52例对照组患者的临床资料,检测PC、PS、ATIII活性等指标,分析抗凝蛋白缺陷与VTE的关系,及患者年龄、性别、临床特征及继发性危险因素。结果:VTE患者的PC、PS、ATIII活性结果与对照组比较明显降低,差异有统计学意义(P < 0.05)。以PS缺陷所占比例最多(18.5%),其次是PC缺陷(13.7%)和ATIII缺陷10.5%),差异具有统计学意义(χ 2 = 25.46, P < 0.05)。复发组与初发组比较抗凝蛋白缺陷发病率差异具有统计学意义(χ 2 = 5.733, P < 0.05),继发性危险因素中前二位是外伤/手术(骨科手术最多)、恶性肿瘤(消化道肿瘤 > 肺癌 > 妇科肿瘤 > 泌尿系肿瘤 > 乳腺癌)。恶性肿瘤合并VTE患者的比例最高。结论:蛋白C (Protein C, PC)、蛋白S (Protein S, PS)和抗凝血酶III (Antithrombin III, ATIII)缺陷是促发VTE发生的重要原发性危险因素,以PS、PC缺陷为主,抗凝蛋白缺陷可能是血栓复发的重要危险因素。继发性危险因素以外伤/手术和恶性肿瘤为主。多种因素并存是引起VTE的重要原因。 Objective: By analyzing the clinical data of 108 patients with VTE, the activity levels of protein C (PC), protein S (PS), antithrombin III (ATIII) were examined, and the relationship between the primary and secondary risk factors and VTE was discussed to provide theoretical basis for the early preven-tion of VTE. Method: The clinical data of 108 cases of VTE (VTE admitted from January 2014 to Janu-ary 2019) and clinical data of 52 patients in the control group were collected to detect the activity of PC, PS and ATIII, analyze the relationship between anticoagulant protein deficiency and VTE, and the age, gender, clinical characteristics and secondary risk factors of patients. Results: The activity of PC, PS and ATIII in VTE patients was significantly lower than that in the control group (P < 0.05). PS defects accounted for the most (18.5%). The difference was statistically significant (χ 2 = 25.46, P < 0.05). The incidence rate of anticoagulant protein deficiency in relapse group was significantly different from that in the initial group (χ 2 = 5.733, P < 0.05). The top two secondary risk factors were trauma/surgery (Department of orthopedics operation), malignant tumor. The proportion of patients with VTE is the highest. Conclusion: The defects of PS, PC and at ATIII are the important primary risk factors for VTE. The defect of anticoagulant protein may be the important risk factors for thrombosis recurrence. The main secondary risk factors were trauma/operation and malignant tumor. The coexistence of many factors is an important cause of VTE.
目的:通过分析108例静脉血栓栓塞症(VTE)患者的临床资料,检查患者蛋白C (PC)、蛋白S (PS)、抗凝血酶III (ATIII)活性水平,探讨原发性和继发性危险因素与静脉血栓栓塞症的关系,为VTE的及早预防提供理论依据。方法:收集克拉玛依市中心医院108例VTE病例组(2014年1月至2019年1月收治的VTE)及52例对照组患者的临床资料,检测PC、PS、ATIII活性等指标,分析抗凝蛋白缺陷与VTE的关系,及患者年龄、性别、临床特征及继发性危险因素。结果:VTE患者的PC、PS、ATIII活性结果与对照组比较明显降低,差异有统计学意义(P < 0.05)。以PS缺陷所占比例最多(18.5%),其次是PC缺陷(13.7%)和ATIII缺陷10.5%),差异具有统计学意义(χ2 = 25.46, P < 0.05)。复发组与初发组比较抗凝蛋白缺陷发病率差异具有统计学意义(χ2 = 5.733, P < 0.05),继发性危险因素中前二位是外伤/手术(骨科手术最多)、恶性肿瘤(消化道肿瘤 > 肺癌 > 妇科肿瘤 > 泌尿系肿瘤 > 乳腺癌)。恶性肿瘤合并VTE患者的比例最高。结论:蛋白C (Protein C, PC)、蛋白S (Protein S, PS)和抗凝血酶III (Antithrombin III, ATIII)缺陷是促发VTE发生的重要原发性危险因素,以PS、PC缺陷为主,抗凝蛋白缺陷可能是血栓复发的重要危险因素。继发性危险因素以外伤/手术和恶性肿瘤为主。多种因素并存是引起VTE的重要原因。
静脉血栓栓塞症,蛋白C蛋白S,抗凝血酶III,继发性危险因素
Fenglei Xu1, Jun Hu2, Laike Zi2, Qin Zhou2, Huiling Jian2, Yizhi Zhang2, Lixia Gao2*
1Department of Neurology of Karamay Central Hospital, Karamay Xingjiang
2Department of Hematology and Oncology, Karamay Central Hospital, Karamay Xingjiang
Received: Apr. 27th, 2022; accepted: May 21st, 2022; published: May 31st, 2022
Objective: By analyzing the clinical data of 108 patients with VTE, the activity levels of protein C (PC), protein S (PS), antithrombin III (ATIII) were examined, and the relationship between the primary and secondary risk factors and VTE was discussed to provide theoretical basis for the early prevention of VTE. Method: The clinical data of 108 cases of VTE (VTE admitted from January 2014 to January 2019) and clinical data of 52 patients in the control group were collected to detect the activity of PC, PS and ATIII, analyze the relationship between anticoagulant protein deficiency and VTE, and the age, gender, clinical characteristics and secondary risk factors of patients. Results: The activity of PC, PS and ATIII in VTE patients was significantly lower than that in the control group (P < 0.05). PS defects accounted for the most (18.5%). The difference was statistically significant (χ2 = 25.46, P < 0.05). The incidence rate of anticoagulant protein deficiency in relapse group was significantly different from that in the initial group (χ2 = 5.733, P < 0.05). The top two secondary risk factors were trauma/surgery (Department of orthopedics operation), malignant tumor. The proportion of patients with VTE is the highest. Conclusion: The defects of PS, PC and at ATIII are the important primary risk factors for VTE. The defect of anticoagulant protein may be the important risk factors for thrombosis recurrence. The main secondary risk factors were trauma/operation and malignant tumor. The coexistence of many factors is an important cause of VTE.
Keywords:Venous Thromboembolism, Protein C Protein S, Antithrombin III, Secondary Risk Factors
Copyright © 2022 by author(s) and Hans Publishers Inc.
This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).
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静脉血栓栓塞症(venous thromboembolism, VTE)起病隐匿,并且临床表现多样化不能早期诊断。及早进行血栓前状态的筛查工作,提高血栓性疾病的诊断,规范血栓栓塞性疾病的防治,彻底扭转对血栓性疾病的认识不足,最终到达早预防、早诊断、早治疗。尽早发现血栓发生的因素,包括凝血酶原G20210A基因突变、蛋白C (Protein C, PC)、蛋白S (Protein S, PS)和抗凝血酶III (Antithrombin III, ATIII)缺陷等在内的遗传因素及环境因素等,做到对此类疾病尽早的筛查,确定易栓症的诊断指标,进一步确定易栓症的高危人群及静脉血栓栓塞症,才能是静脉血栓的防治越来越多规范。因此,本研究针对血栓前状态及易栓症疾病的病因、发病危险因素等分析,目的在于更好防治此类疾病、降低发病率、减少医疗费用,提高人们的生活质量。
静脉血栓栓塞症(venous thromboembolism, VTE)是一种危害人类健康和生命的常见疾病,有较高的发病率和死亡率 [
病例为2014年6月至2019年6月于我院就诊的108例下肢DVT伴或不伴PE患者的临床资料,调查表填写病人年龄、性别、既往病史、手术外伤史、吸烟史、基础疾病等相关资料。其中男性66例,女性42例,年龄17~86岁,中位年龄67岁。按治疗分为初治组还是复治组。并同时经医院伦理委员会讨论批准。
入组对象均为同期于我院行体检的健康者共52例,其中男性36例,女性26例,年龄18~86岁,中位年龄68岁。观察组与对照组的一般情况(年龄、性别)进行对比发现2组在年龄、性别方面无差异(P > 0.05)。
DVT的诊断标准参照《静脉血栓形成的诊断和治疗指南》2021版 [
1) 患者近期有手术、严重外伤、骨折或肢体制动、长期卧床、肿瘤等病史,出现下肢肿胀、疼痛、小腿后方和/或大腿内侧有压痛时,提示下肢DVT的可能性大.
2) 辅助检查
① 彩色多普勒超声检查:经彩色多普勒血流显像(CDFI)检查显示下肢深静脉管腔阻塞。该检查对股腘静脉血栓诊断的准确率高(>90%),对周闱型小腿静脉丛血栓和中央型髂静脉血栓诊断的准确率较低。如连续两次超声检查均为阴性,对于低度可能的患者可以排除诊断,而对于高、中度可能的患者,建议作血管造影等影像学检查。
② CT静脉成像:怀疑PE的者行超高速螺旋CT肺动脉造影(CTPA);肺动脉造影;主要用于下肢主干静脉或下腔静脉血栓的诊断,准确性高,联合应用CTV及CT肺动脉造影检查,可增加VTE的确诊率。
③ 核磁静脉成像:静脉成像、静脉造影任意一项检查显示下肢深静脉管腔阻塞或充盈缺损改变。能准确显示髂、股、腘静脉血栓,但不能很好地显示小腿静脉血栓。尤其适用于孕妇,时且无需使用造影剂,但有固定金属植入物及心脏起搏器植入者,不可实施此项检查。
④ 静脉造影:准确率高,不仅可以有效判断有无血栓、血栓部位、范围、形成时间和侧支循环情况,而且常被用來评估其他方法的诊断价值,目前仍是诊断下肢DVT的金标准。
⑤ D-二聚体(D-dimer, DD)升高 > 500 ug/L (ELISA法)具有重要参考价值。
以上检测相互结合做出诊断。
反复超声检查及影像学检查不能明确诊断DVT或PE者。2周内应用抗凝溶栓药物者不行抗凝蛋白检测及一周内行静脉置管者。严重肝肾、血液疾病患者。
所有数据应用SPSS19.0软件进行分析。均数比较采用t检验;组间差异显著性采用t检验;计数资料采用率值表示,组间比较应用χ2检验,检验水准为α = 0.05。相关分析采用双变量Pearson相关分析及Logistic回归分析。
男性与女性的年龄分布构成比差异无统计学意义(χ2 = 2.645, P = 0.76),VTE初发高峰年龄为40~80岁。108例VTE患者的临床表现分别是肿胀105例(97.2%)、疼痛85(78.7%)、皮温增高32 (29.6%)、色素沉着9例(8.3%)、静脉曲张6例(5.5%),肿胀和疼痛是常见的临床症状。108例患者DVT合并PE者14人,占总数的12.9%。
观察组 PC、PS、ATIII活性水平与对照组比较明显降低,差异有统计学意义 (P < 0.05) (见表1)。观察组108例患者中48例出现抗凝蛋白缺陷,其中单纯PS缺陷20例,单纯PC缺陷9例,单纯ATIII缺陷7例,复合缺陷9例,包括PC + PS缺陷4例,PC + ATIII缺陷2例,PS + ATIII缺陷2例,PC + PS + ATIII缺陷1例。抗凝蛋白缺陷以PS缺陷所占比例最多(18.5%),抗凝蛋白的总缺陷率为44.4%。对照组仅1例PS (1.9%)缺陷。观察组与对照组抗凝蛋白缺陷发病率比较差异具有统计学意义(χ2 = 25.46, P < 0.05) (见表2)。
Project | Number of cases | PS (%) | PC (%) | ATIII (%) | PLT (×109/L) | FIB (g/L) | D-D (ug/mL) |
---|---|---|---|---|---|---|---|
Group Control group | 108 52 T P | 72.33 ± 23.21 93.62 ± 21.02 4.838 0.000 | 88.03 ± 21.5 103.11 ± 36.51 2.735 0.025 | 63.16 ± 28.43 102.11 ± 23.51 7.648 0.000 | 465.18 ± 33.66 196.21 ± 45.06 5.102 0.000 | 4.46 ± 3.18 2.08 ± 1.32 8.587 0.000 | 0.95 ± 0.23 0.26 ± 0.35 12.456 0.000 |
表1. 观察组与对照组凝血指标水平的比较( x ¯ ± s )
Anticoagulant protein deficiency | Observation group [n (%)] | Control group [n (%)] |
---|---|---|
Simple PS defect Simple PC defect Simple at III defect PC + PS defect PC + at III defect PS + at III defect PC + PS + at III defect | 20 (18.5) 9 (8.3) 7 (6.4) 4 (3.7) 2 (1.8) 2 (1.8) 1 (0.9) | 1 (1.9) 0 0 0 0 0 0 |
表2. 观察组与对照组抗凝蛋白缺陷情况比较[n(%)]
108例检测抗凝蛋白患者中有19例为复发患者,89例为初发患者,其中复发组中有12例抗凝蛋白缺陷,初发组有31例抗凝蛋白缺陷,两组比较抗凝蛋白缺陷发病率差异具有统计学意义(χ2 = 6.102, P < 0.05),复发组患者PC、PS、ATIII活性水平明显低于初发组(P < 0.05) (见表3)。提示抗凝蛋白缺陷可能是血栓复发的重要原因。
Project | Number of cases | PS (%) | PC (%) | ATIII (%) | Defective patients |
---|---|---|---|---|---|
Initial development group Recurrence group | 89 19 T (χ2) P | 72.33 ± 23.21 93.62 ± 21.02 4.958 0.000 | 88.03 ± 21.5 103.11 ± 36.51 3.547 0.000 | 63.16 ± 28.43 102.11 ± 23.51 2.648 0.009 | 31 (34.8%) 12 (63.2%) 6.102 0.001 |
表3. 初发组与复发组抗凝蛋白活性水平及缺陷比较
本研究显示目前公认的继发性危险因素中,居前二位的是外伤和(或)手术52例(48.1%),恶性肿瘤22例(20.3%) (见表4)。在外伤和(或)手术危险因素中,骨科手术14例(26.9%),比例最高。恶性肿瘤并VTE患者比例最高的是消化道肿瘤8例(36.4%),其次为妇科肿瘤 > 肺癌 > 泌尿系肿瘤 > 乳腺癌。可能的危险因素中,居前二位的是高血压病(24.2%)、吸烟(16.6%) (见表5)。
Secondary risk factors of VTE | patient n (%) |
---|---|
Trauma and/or surgery Malignant tumor History of venous thrombosis Old age (>75 years) Antiphospholipid antibody positive Stroke sequelae long-term bed rest Varicose veins of lower extremities Steroid hormone application Long term oral contraceptive Hyperhemoglobinemia Peripheral venous catheterization | 52 (48.1) 22 (20.3) 18 (16.7) 17 (17.7) 13 (12.0) 9 (8.3) 8 (7.4) 7 (6.5) 4 (3.7) 2 (1.8) 2 (1.8) |
表4. 公认的VTE继发性危险因素分析
Possible VTE acquired risk factors | Patient n (%) |
---|---|
Hypertension Smoking Hypoproteinemia Hyperlipidemia Multiple myeloma Diabetes Chronic cardiac insufficiency Chronic obstructive pulmonary disease Renal insufficiency Cirrhosis Systemic connective tissue disease | 26 (24.2) 18 (16.6) 14 (12.9) 13 (12.0) 8 (7.4) 6 (5.5) 5 (4.6) 4 (3.7) 3 (2.8) 2 (1.9) 1 (0.9) |
表5. 可能的VTE继发性危险因素分析
在108例VTE患者中,继发性危险因素2种及2种以上的占70.3%,原发与继发性危险因素并存的占36.9% (见表6)。表明VTE的发生是多因素引起的疾病。
Types of risk factors | Number of cases | Two factors | More than 3 factors |
---|---|---|---|
Coexistence of secondary factors Coexistence of primary and secondary factors | 108 73 | 46 (42.6) 16 (21.9) | 30 (27.8) 11 (13.9) |
表6. 多种VTE易栓危险因素并存分析[n(%)]
DVT是临床上常见的疾病,其发病率呈逐年上升趋势 [
我们通过总结克拉玛依市中心医院5年来住院VTE患者的资料,发现与国内外报道的一样,VTE的初次发作的年龄高峰为50~70岁,男性发病高峰年龄较女性提早10年,其原因目前尚不清。本组病例的临床表现以下肢肿胀105 (97.2%)、和下肢疼痛85 (78.7%)为主,一般往往两种症状同时出现。合并肺动脉栓塞者的占12.6%。随着人们对DVT的认识加强,临床上对DVT的警惕性也不断提高。一旦出现相应的临床症状,通过实验室血浆D-二聚体测定及多普勒超声检查一般可以确诊。
血栓栓塞症相关危险因素分获得性危险因素和遗传易栓因素。国外报道的常见获得性危险因素大多为外伤(或)手术、肿瘤和抗磷脂抗体阳性 [
Souto [
研究认为VTE的发生是潜在的遗传易栓性和获得性因素相结合导致的突发事件 [
新疆自治区自然科学基金项目:2022D01A22。
许风雷,胡 军,孜莱克,周 琴,菅辉玲,张益枝,高丽霞. 静脉血栓栓塞症的原发性及继发性危险因素分析Analysis of the Primary and Secondary Risk Factors of Venous Thromboembolism[J]. 临床医学进展, 2022, 12(05): 4877-4884. https://doi.org/10.12677/ACM.2022.125707