Casini Alessandro, Moerloose Philippe de, Neerman-Arbez Marguerite
Division of Angiology and Hemostasis, University Hospitals of Geneva, Geneva, Switzerland.
Department of Medicine, University of Geneva, Geneva, Switzerland.
Semin Thromb Hemost. 2025 Mar;51(2):103-110. doi: 10.1055/s-0044-1788898. Epub 2024 Aug 16.
Congenital fibrinogen disorders (CFDs) include afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. The fibrinogen levels, the clinical features, and the genotype define several sub-types, each with specific biological and clinical issues. The diagnosis of CFDs is based on the measurement of activity and antigen fibrinogen levels as well as on the genotype. While relatively easy in quantitative fibrinogen disorders, the diagnosis can be more challenging in qualitative fibrinogen disorders depending on the reagents and methods used, and the underlying fibrinogen variants. Overall, quantitative and qualitative fibrinogen defects lead to a decrease in clottability, and usually in a bleeding tendency. The severity of the bleeding phenotype is moreover related to the concentration of fibrinogen. Paradoxically, patients with CFDs are also at risk of thrombotic events. The impact of the causative mutation on the structure and the fibrinogen level is one of the determinants of the thrombotic profile. Given the major role of fibrinogen in pregnancy, women with CFDs are particularly at risk of obstetrical adverse outcomes. The study of the fibrin clot properties can help to define the impact of fibrinogen disorders on the fibrin network. The development of next generation sequencing now allows the identification of genetic modifiers able to influence the global hemostasis balance in CFDs. Their integration in the assessment of the patient risk on an individual scale is an important step toward precision medicine in patients with such a heterogeneous clinical course.
先天性纤维蛋白原异常（CFDs）包括无纤维蛋白原血症、低纤维蛋白原血症、异常纤维蛋白原血症和低异常纤维蛋白原血症。纤维蛋白原水平、临床特征和基因型定义了几种亚型，每种亚型都有特定的生物学和临床问题。CFDs的诊断基于活性和抗原纤维蛋白原水平的测定以及基因型。虽然在定量纤维蛋白原异常中相对容易，但在定性纤维蛋白原异常中，根据所使用的试剂和方法以及潜在的纤维蛋白原变体，诊断可能更具挑战性。总体而言，定量和定性纤维蛋白原缺陷会导致凝血性降低，通常还会导致出血倾向。出血表型的严重程度还与纤维蛋白原浓度有关。矛盾的是，CFDs患者也有发生血栓事件的风险。致病突变对结构和纤维蛋白原水平的影响是血栓形成特征的决定因素之一。鉴于纤维蛋白原在妊娠中的主要作用，患有CFDs的女性尤其有发生产科不良结局的风险。对纤维蛋白凝块特性的研究有助于确定纤维蛋白原异常对纤维蛋白网络的影响。新一代测序技术的发展现在能够识别能够影响CFDs中全球止血平衡的基因修饰因子。将它们整合到个体层面的患者风险评估中是朝着对具有如此异质临床过程的患者进行精准医学迈出 的重要一步。
