摘要
目的探讨先天性纤维蛋白原病的基因突变类型与分型、临床表现、实验室检查、诊断及纤维蛋白原替代治疗情况。方法对2003年4月至2020年11月就诊于中国医学科学院血液病医院的146例先天性纤维蛋白原病患者进行回顾性分析。结果146例患者中,男61例(41.8%),女85例(58.2%),就诊时中位年龄为33.5岁;共采集到98例患者的临床症状学信息,34例(34.7%)因出血症状而就诊,33例(33.7%)因手术前检查而确诊,55例(56.1%)患者至少有1次出血,42例(42.9%)无出血表现。纤维蛋白原活性(FIB∶C)与ISTH-BAT出血评分之间呈负相关(rs=-0.412,P<0.001)。在56例患者中检出34种基因突变(包括新突变16种),其中84.1%为错义突变,FGA外显子2和FGG外显子8突变占全部突变位点的71.4%。无纤维蛋白原血症患者(7例)中位年龄为2(1~12)岁,ISTH-BAT评分为4分;异常纤维蛋白原血症患者(50例)中位凝血酶时间为28.5(19.2~36.6)s。输注纤维蛋白原后1 h、24 h的活性回收率(IVR)分别为(127.19±44.03)%、(101.78±43.98)%。输注纤维蛋白原后,FIB∶C明显提升,凝血酶时间及凝血酶原时间明显下降,用药24 h后凝血酶时间较基线平均下降(15.2±12.1)%。结论多数先天性纤维蛋白原缺乏症患者症状轻微或无症状;无纤维蛋白原血症患者出血症状较为严重,FIB∶C与出血程度之间存在负相关;基因检测有助于疾病分型诊断;FIB∶C/纤维蛋白原抗原(FIB∶Ag)比值<0.7可作为临床分型依据。凝血酶时间可作为异常纤维蛋白原血症诊断及纤维蛋白原替代治疗的疗效判定依据。
Objective To investigate the clinical type and gene mutations,clinical manifestations,laboratory tests,diagnosis,and fibrinogen replacement therapy of congenital fibrinogen disorders.Methods Clinical data of 146 patients with congenital fibrinogen disorders diagnosed from April 2000 to November 2020 were retrospectively analyzed.Results Among the 146 patients,61(41.8%)men and 85(58.2%)women had a median age of 33.5 years at the time of consultation.34 patients(34.7%)were found to suffer from the disease due to bleeding symptoms,33 patients(33.7%)due to preoperative examination.55 patients(56.1%)had at least one bleeding symptom,and 42 patients(42.9%)had no bleeding symptoms.There is a negative correlation between fibrinogen activity concentration and bleeding ISTH-BAT score(rs=-0.412,P=0.001).A total of 34 gene mutations were detected in 56 patients,of which 84.1%were missense mutations,and 16 new mutations were found.FGA Exon2 and FGG Exon8 mutations accounted for 71.4%of all mutation sites.Patients with afibrinogenemia were younger,with a median age of 2(1-12)years,an ISTH-BAT score of 4,and patients with dysfibrinogenemia had significantly longer thrombin time(TT),with a median of 28.5(19.2-36.6)s.The 1 hour in vivo recovery(IVR)after fibrinogen infusion was(127.19±44.03)%,and the 24 hour IVR was(101.78±43.98)%.In addition to the obvious increase in the concentration of fibrinogen activity,the TT and the prothrombin time(PT)both decreased significantly,and the TT decreased more significantly,with an average decrease of 15.2%compared to the baseline after 24 hours of infusion.Conclusion Most patients with congenital fibrinogen disorders have mild or no bleeding symptoms.Patients with afibrinogenemia have more severe symptoms.There is a negative correlation between the fibrinogen and the degree of bleeding.Genetic testing is helpful for the diagnosis of disease classification.FIB∶C/FIB∶Ag<0.7 can be used as a basis for clinical diagnosis.The TT can be used as the basis for the diagnosis of dysfibrinogenemia and the effectiveness of fibrinogen infusion.
作者
黄丽颖
张冬雷
付荣凤
刘葳
陈云飞
薛峰
刘晓帆
毕婷婷
杨仁池
张磊
Huang Liying;Zhang Donglei;Fu Rongfeng;Liu Wei;Chen Yunfei;Xue Feng;Liu Xiaofan;Bi Tingting;Yang Renchi;Zhang Lei(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Tianjin Laboratory of Blood Disease Gene Therapy,CAMS Key Laboratory of Gene Therapy for Blood Diseases,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2021年第7期555-562,共8页
Chinese Journal of Hematology
基金
国家重点研发计划(2019YFA0110802)
国家自然科学基金(81970121、82000136、81600099)
天津市应用基础与前沿技术研究计划(19JCZDJC33000、18JCQNJC11900)
中央级公益性科研院所基本科研业务费(2019PT310022)。
关键词
先天性纤维蛋白原缺陷症
基因突变
热点突变
临床表型
Congenital fibrinogen disorders
Gene mutation
Hot spot mutation
Clinical manifestation