5例儿童遗传性凝血因子ⅩⅢ缺陷症的临床资料分析  

Analysis of clinical data of five children with inherited factor ⅩⅢ deficiency

作　　者：刘会青 何丽雅 张永红[3] 熊雨美 徐涛 朱天闻[3] 吴润晖[1] Liu Hui-qing;He Li-ya;Zhang Yong-hong;Xiong Yu-mei;Xu Tao;Zhu Tian-wen;Wu Run-hui(Hematology Center,Beijing Key Laboratory of Pediatric Hematology Oncology,National Key Discipline of Pediatrics(Capital Medical University),Key Laboratory of Major Diseases in Children,Ministry of Education,Beijing Children's Hospital,Capital Medical University,National Center for Children's Health,Beijing 100045,China;Guangzhou Women and Children's Medical Center Guangzhou,Guangzhou 510000,China;Department of Neonatology,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China)

机构地区：[1]国家儿童医学中心首都医科大学附属北京儿童医院血液病中心儿童血液病与肿瘤分子分型北京市重点实验室儿科学国家重点学科儿科重大疾病研究教育部重点实验室,北京100045 [2]广州市妇女儿童医疗中心儿内科,广州510000 [3]上海交通大学医学院附属新华医院新生儿内科,上海200092

出　　处：《血栓与止血学》2022年第5期1146-1151,共6页Chinese Journal of Thrombosis and Hemostasis

基　　金：北京市科委首都临床特色应用研究(Z181100001718182);首都卫生发展科研专项项目(首发2018-2-2094);首都医科大学附属北京儿童医院儿童用药专项(YZZD202003);国家科技重大专项(2017ZX09304029001)。

摘　　要：目的探讨遗传性凝血因子ⅩⅢ缺陷症(FⅩⅢD)的临床特征及诊疗要点。方法回顾性病例总结。分析2017年8月至2020年10月在首都医科大学附属北京儿童医院、广州市妇女儿童医疗中心、上海交通大学医学院附属新华医院3家三甲医院诊治的5例遗传性FⅩⅢD患儿的临床资料。结果5例遗传性FⅩⅢD患儿,男2例,女3例,均无阳性家族史,中位诊断年龄5岁(13天~12岁)。首次出血:4例(80%)生后脐部渗血,1例(20%)皮肤出血;并发症:1例因牙龈出血致牙齿脱落,1例球结膜出血致脱垂。5例血小板计数及常规凝血检测均正常。4例行FⅩⅢ定性检测,结果均为阳性。5例均存在F13A1基因突变:3例为纯合突变,2例为复合杂合突变;其中5个位点既往无报道:c.1347delC(p.T450Lfs*15);c.1352_1353del(p.H451Rfs*29);c.2015G>A(p.G672E);(c.799-1G>T);chr6:6224294-6224944。5例均曾接受新鲜冰冻血浆替代治疗,且可有效止血:1例规律预防治疗,4例接受按需治疗。随访时间为10月~4年,5例均存活。结论遗传性FⅩⅢD以出生时脐部出血、日常生活中皮肤黏膜反复出血为主要表现,出血症状轻重不一;对常规出凝血检测正常但反复出血的患儿需要进行FⅩⅢ相关检测,而进一步完善基因检测有助于诊断;开展有效的替代治疗可以有效防控出血。Objective To explore the clinical characteristics and management approaches for inherited factorⅩⅢdeficiency(FⅩⅢD)in children.Methods The clinical data of 5 children with inherited FⅩⅢD hospitalized in Beijing Children’s Hospital,Capital Medical University,Guangzhou Women and Children’s Medical Center and Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from August 2017 to October 2020 were analyzed retrospectively.Results Among the 5children with inherited FⅩⅢD diagnosed,there were 2 males and 3 females,none of them had positive family history.The median age of diagnosis was 5 years old(13 days to 12 years old).Initial bleeding was umbilical cord bleeding(UCB)in 4 case(80%)and the dermal ecchymosis in 1 case(20%).Complications included teeth loss due to gingival bleeding in 1 case,and prolapse of bulbar conjunctiva as a result of conjunctival hemorrhage in 1 case.Blood tests showed that platelet count and coagulation tests were all normal in the five cases.FⅩⅢqualitative test was positive in 4 cases.All 5 children had mutations at different loci of F13A1 gene,among which 3 cases were homozygous mutation and 2 cases were complex heterozygous mutation.5 loci were unreported previously,details are as follows:c.1347delC(p.T450Lfs*15),c.1352_1353del(p.H451Rfs*29),c.2015G>A(p.G672E),c.799-1G>T,chr6:6224294-6224944.The patients all received frozen plasma infusion,which could effectively stop bleeding.1 case received regular preventive treatment and 4 cases were treated on-demand when they had bleeding.The follow-up was 10 months-4 years,all the children survived.Conclusions The main clinical manifestations of inherited FⅩⅢD are umbilical cord bleeding at birth and repeated bleeding of skin and mucosa in daily life,and the severity of bleeding symptoms is different.FⅩⅢrelated tests were needed for children with normal routine bleeding and coagulation tests but had repeated bleeding,and further improving genetic testing is helpful for diagnosis;Effective replac

关 键 词：遗传性凝血因子ⅩⅢ缺陷症 出血 儿童 基因 

分 类 号：R554.9[医药卫生—血液循环系统疾病]