113例静脉血栓栓塞症患者遗传性抗凝蛋白缺陷分析  

Hereditary anticoagulant protein deficiency in 113 patients with venous thromboembolism

作　　者：徐琦煜[1] 金艳慧[1] 杨丽红[1] 李小龙[1] 刘斯奇 王明山[1] XU Qiyu;JIN Yanhui;YANG Lihong;LI Xiaolong;LIU Siqi;WANG Mingshan(Center of Laboratory Medicine,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325015,China)

机构地区：[1]温州医科大学附属第一医院医学检验中心,325015

出　　处：《浙江医学》2021年第4期391-394,400,共5页Zhejiang Medical Journal

基　　金：温州市基础性科研项目(Y20190471)。

摘　　要：目的探讨静脉血栓栓塞症(VTE)患者的遗传性抗凝蛋白缺陷及其临床特点。方法选取2019年6月至2020年4月温州医科大学附属第一医院收治的无明显诱因VTE患者113例,检测患者3种抗凝蛋白即蛋白C(PC)、蛋白S(PS)及抗凝血酶(AT)活性并计算缺陷发生率,分析临床表现特点。采用DNA测序法进行相关基因突变的分析。结果113例VTE患者中抗凝蛋白总缺陷率为29.20%(33例),其中单纯PS缺陷16例(14.16%),涉及的突变基因有c.1351C>T、c.-168C>T、c.1165G>T、c.2001A>G、c.1776T>A、c.1095T>G;单纯PC缺陷7例(6.19%),涉及的突变基因有c.1212-1212del G、c.970G>A、c.565C>T、c.1318C>T、c.532G>C、c.833T>C;单纯AT缺陷3例(2.65%),涉及的突变基因有c.1346T>A、c.851T>C、c.318319ins T;复合缺陷7例(6.19%),其中PC+AT 2例,突变基因分别为c.565C>T+c.1358T>C和c.7271G>A+c.922G>T;PC+PS 3例,突变基因分别为c.997A>G+c.1351C>T、c.565C>T+?、c.383G>A+?;PS+AT 2例,突变基因分别为c.3137C>T+c.1680T>A和?+c.5890-5892delctt。其中PC基因突变的c.1318C>T和c.833T>C以及AT基因突变的c.1346T>A和c.851T>C为新发现的突变。33例抗凝蛋白缺陷患者中深静脉血栓形成20例(60.61%),颅内静脉窦血栓形成7例(21.21%),肺栓塞6例(18.18%);颅内静脉窦血栓形成患者均为PS缺陷。结论VTE患者遗传性抗凝蛋白缺陷率较高,可能是温州地区VTE患者常见的遗传性危险因素,其中以PS缺陷最为多见,且PS缺陷可能是无明显诱因颅内静脉窦血栓形成的一个重要危险因素。Objective To analyze the hereditary anticoagulant protein deficiency and clinical characteristics in patients with venous thromboembolism(VTE).Methods From June 2019 to April 2020,a total of 113 patients with VTE without obvious inducement who were admitted to the First Affiliated Hospital of Wenzhou Medical University,were enrolled.The protein C(PC),protein S(PS)and antithrombin(AT)activity were tested,the incidence of defects were calculated,clinical data were analyz to analyze.Results The overall prevalence rate of deficiency in 113 VTE patients was 29.20%(n=33).PS deficiency was the most frequent(16/113,14.16%),the mutant genes involved c.1351 C>T,c.-168 C>T,c.1165 G>T,c.2001 A>G,c.1776 T>A and c.1095 T>G.Seven patients had PC deficiency(6.19%),the mutant genes involved c.1212-1212 del G,c.970 G>A,c.565 C>T,c.1318 C>T,c.532 G>C,c.833 T>C.Three patients had AT deficiency(2.65%),the mutant genes involved c.1346 T>A,c.851 T>C,c.318319 ins T.Seven patients had combined deficiency(6.19%),among whom 2 cases had PC+AT deficiency,the mutant genes were c.565 C>T+c.1358 T>C and c.7271 G>A+c.922 G>T.Three cases had PC+PS deficiency,the mutant genes were c.997 A>G+c.1351 C>T,c.565 C>T+?,C.383 G>A+?.Two cases had PS+AT,the mutant genes were c.3137 C>T+c.1680 T>A and?+c.5890-5892 delctt.The PC gene mutation c.1318 C>T,c.833 T>C and AT gene mutation c.1346 T>A,c.851 T>C were discovered for the first time.Among 33 patients with defects,20 patients(60.61%)had deep vein thrombosis,7 patients(21.21%)had intracranial venous sinus thrombosis and 6 patients(18.18%)had pulmonary embolism.All 7 patients with intracranial venous sinus thrombosis had PS deficiency.Conclusion VTE patients have a higher rate of hereditary anticoagulant protein deficiency,which may be a common genetic risk factor for VTE patients in Wenzhou area.Among them,PS deficiency is the most common,which may be an important influencing factor for unprovoked intracranial venous sinus thrombosis.

关 键 词：遗传性抗凝蛋白 静脉血栓栓塞 易栓症 复合缺陷 Ⅰ型抗凝血酶缺陷 

分 类 号：R543.6[医药卫生—心血管疾病]