以自发性脑出血为首发表现的遗传性异常纤维蛋白原血症一例

A Case of Hereditary Dysfibrinogenemia with Spontaneous Intracerebral Hemorrhage as the Initial Manifestation

摘要: 目的：报告1例以自发性脑出血为首发表现的遗传性异常纤维蛋白原血症，以提高临床对该病罕见严重表型的认识。方法：回顾性分析1例49岁女性患者的临床资料、凝血功能动态变化、基因检测结果及家系调查情况。结果：患者以突发意识障碍为首发表现，头颅CT示左侧基底节巨大血肿，急诊行开颅血肿清除术。凝血功能示纤维蛋白原活性低于检测下限，抗原4.93 g/L，凝血酶时间延长。基因检测示FGA基因c.104G>A (p.R35H)杂合突变，ACMG分级致病。家系调查显示其女儿纤维蛋白原0.43 g/L但无症状。经围手术期纤维蛋白原替代及综合治疗，病情好转出院，随访3个月无再出血。结论：遗传性异常纤维蛋白原血症可长期无症状，在高血压等诱因下可发生严重自发性脑出血。对出血程度与危险因素不相称的患者，应及时完善纤维蛋白原活性/抗原比值检测及基因筛查以明确诊断。

Abstract: Objective: To report a case of hereditary dysfibrinogenemia presenting with spontaneous intracerebral hemorrhage as the initial manifestation, in order to improve clinical awareness of the rare severe phenotype of this disease. Methods: The clinical data, dynamic changes in coagulation function, genetic testing results, and pedigree investigation of a 49-year-old female patient were retrospectively analyzed. Results: The patient presented with sudden disturbance of consciousness. Cranial CT revealed a huge hematoma in the left basal ganglia, and emergency craniotomy with hematoma evacuation was performed. Coagulation tests showed that fibrinogen activity was below the lower limit of detection, fibrinogen antigen was 4.93 g/L, and thrombin time was prolonged. Genetic testing revealed a heterozygous mutation of c.104G>A (p.R35H) in the FGA gene, which was classified as pathogenic according to ACMG criteria. Pedigree investigation showed that her daughter had a fibrinogen level of 0.43 g/L but remained asymptomatic. After perioperative fibrinogen replacement and comprehensive treatment, the patient improved and was discharged, with no rebleeding during 3 months of follow-up. Conclusion: Hereditary dysfibrinogenemia may remain asymptomatic for a long time but can lead to severe spontaneous intracerebral hemorrhage when triggered by hypertension or other predisposing factors. For patients with hemorrhage severity disproportionate to risk factors, fibrinogen activity/antigen ratio testing and genetic screening should be performed promptly to establish a definite diagnosis.