新生儿凝血因子Ⅶ缺乏症2例报告并文献复习

Factor Ⅶ deficiency in newborns: a report of two cases and literature review

目的探讨新生儿期发病的遗传性凝血因子Ⅶ缺乏症(FⅦD)的临床特征、诊断和治疗。方法对广州市妇女儿童医疗中心确诊的2例新生儿FⅦD的临床表现、诊治过程和基因检测情况进行回顾性分析,并通过复习相关文献,分析和总结有关国内外新生儿FⅦD的文献报道。结果 2例FⅦD患儿均为女性,临床表现为严重消化道和颅内出血,实验室特点为反复、非Vit K1依赖的凝血酶原时间(PT)持续延长,部分凝血酶原时间(APTT)正常,凝血因子Ⅶ活性分别为1.5%和3%,分别于31 d和6个月再次发生大面积颅内出血而死亡,基因检测证实均为F?基因IVS7+1G>T剪切位点纯合突变。文献复习共检索到22例新生儿期FⅦD,合并本文2例后共24例。24例均为足月,男女均可发病,多为生后7 d内发病(17/24,70.8%);首发症状依次为消化道出血9例、神经系统症状(嗜睡、抽搐和反应差等) 8例、皮肤苍白7例。颅内出血比例高(23/24); PT显著延长,Ⅶ因子活性明显下降(≤5%占83.3%);病死率及致残率高(70.8%); 14例经基因检测确诊。结论 FⅦD在新生儿期发病罕见,一旦发病,易发生致命性出血,预后不良。PT延长且不易纠正,Ⅶ因子活性显著下降即可临床诊断,F?基因某些位点突变可导致严重出血,基因诊断有助于产前诊断。

Objective To investigate the clinical features,diagnosis and treatment of inherited coagulation factor Ⅶ deficiency(FⅦD)in newborns.Methods The clinical manifestations,diagnosis and treatment process,and genetic testing of two cases of neonatal FⅦD diagnosed at Guangzhou Women and Children's Medical Center were retrospectively analyzed.The literature about the clinical features of FⅦD in the neonatal period was reviewed and summarized.Results Two female cases of FⅦD presented with severe gastrointestinal tract and intracranial hemorrhage.Their laboratory tests were characterized by repeated and non-VitK 1-dependent prothrombin time(PT)prolongation and normal activated partial thromboplastin time(APTT).The factor Ⅶ activity was 1.5% and 3% respectively.These two cases both died of a large area of intracranial hemorrhage at 31 days and 6 months after birth respectively.Gene sequencing results showed a homozygous mutation in the F gene IVS7+1G>T cleavage site in both two cases.In addition,we reviewed 24 cases of full-term neonatal FⅦD of both sexes.Among them,22 cases were reported by the literature,and 2 by this report.Most of newborns(73.7%)had the first onset of the disease mostly within 7 days after birth.The main initial symptoms of disease onset included gastrointestinal bleeding(blood stool,vomiting blood)(9/24),nervous system signs(drowsiness,convulsions,poor response)(8/24)and pale skin(7/24).The proportion of intracranial hemorrhage was high(23/24).PT was significantly prolonged,and FⅦ activity was significantly decreased(≤5% accounting for 83.3%).The incidence of mortality and disability was 70.8%(17/24).Fourteen of 24 babies got positive F gene diagnosis.Conclusion FⅦD is a rare disease in the neonatal period.Once the disease occurs,life-threatening bleeding is prone to occur and the prognosis is always poor.FⅦD can be clinically confirmed with the presence of prolonged PT that is difficult to correct and significantly decreased FⅦ activity.As mutations in some sites of F gene can cause severe bleeding,a genetic diagnosis contributes to prenatal diagnosis.