One case of abnormal fibrinogenemia and literature review

Objective To explore the clinical characteristics, diagnosis and treatment of abnormal fibrinogenemia. Methods On July 30, 2018, one case of patient with abnormal fibrinogenemia who was admitted at First People′s Hospital of Zigong was selected as the research subject. The patient was female, and 52 years old. The tests of pure tone audiometry, coagulation function were performed in this patient. And FGA, FGB and FGG genes of patients were sequenced. Patient was diagnosed and treated based on her clinical manifestations, laboratory test results. Follow-up was conducted until August 2019. Retrospective analysis method was used to collect the clinical data of this patient, and to analyze her clinical manifestations, diagnosis and treatment process. In addition, China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform, PubMed database were searched for the same case reports as the patient′s genetic mutation. The retrieval time is from the database inception to December 31, 2018. This article summarizes types of genetic mutations related to this patient with abnormal fibrinogenemia, patients′ bleeding and thrombotic symptoms, and so on. This study meets the requirements of the World Medical Association Declaration of Helsinki revised in 2013. Results ① On July 30, 2018, the patient was admitted to Department of Otorhinolaryngology of First People′s Hospital of Zigong due to " left hearing loss for 1+ months" . The patient complained of tinnitus, dizziness, low back pain, no oral cavity and gingival bleeding, no subcutaneous petechiae and ecchymosis, no hemoptysis, no abdominal pain and diarrhea, no black stools, etc.. The patient was in good health, and there was no history of bleeding and thrombosis in the first and second degree relatives of the family. ② After the patient was admitted, pure tone audiometry showed that moderate-severe sensorineural hearing loss of the left ear. Results of coagulation function test showed that prothrombin time (PT) was 11.3 s, activated partial thromboplastin time (APTT) was 23.4 s, thrombin time (TT) was 48.4 s, and fibrinogen value was 0.31 g/L. ③ Sequencing results of the FGA gene of this patient showed that c. 104G>A (p.Arg35His) missense mutation in exon 2 and c. 16A>G (p.Ile6Val) missense mutation in exon 1, and all were heterozygous mutations. ④ The patient was diagnosed with abnormal fibrinogenemia and left sensorineural hearing loss. Given that the patient and family members had no history of bleeding and thrombotic diseases, the patient had no oral and gum bleeding; no subcutaneous petechiae, ecchymosis, hematemesis, hemoptysis; no bleeding tendency such as melena, the patient was not given special treatment such as fibrinogen infusion, but only clinical observation. At end of follow-up, general condition of the patient was good. ⑤ The results of literature review showed that patients of abnormal fibrinogenemia with c. 104G>A (p.Arg35His) heterozygous mutation in exon 2 and c. 16A>G (p.Ile6Val) heterozygous mutation in exon 1 of FGA gene, which were the same mutations of the patient in this study, were 23 and 1 cases, respectively. Among them, only 2 patients with c. 104G>A (p.Arg35His) heterozygous mutation in exon 1 of FGA gene showed bleeding and thrombosis symptoms. Conclusions Abnormal fibrinogenemia has a variety of clinical manifestations. Some patients manifest as without any clinical symptoms, but others can also manifest as bleeding or thrombosis. The diagnosis of the disease is mainly based on its family history, clinical manifestations, abnormal results of blood coagulation tests, identification of genetic mutations, and adheres to the principle of individualization. No special treatment is required for asymptomatic abnormal fibrinogenemia patients without a history and family history of bleeding and thrombosis. Key words: Fibrinogens, abnormal; Mutation; Fibrinogen; Hemorrhage; Thrombosis; Abnormal fibrinogenemia