146例先天性纤维蛋白原病的基因突变谱及纤维蛋白原输注药代动力学分析

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.