Division of Angiology and Hemostasis, University Hospitals of Geneva, Geneva, Switzerland.
Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Semin Thromb Hemost. 2022 Nov;48(8):880-888. doi: 10.1055/s-0042-1756187. Epub 2022 Sep 2.
Congenital fibrinogen disorders encompass a broad range of fibrinogen defects characterized by a wide molecular and clinical spectrum. From the first clinical description of afibrinogenemia in 1920, many major achievements have contributed to a better understanding of these complex disorders. The finding of causative mutations in all three fibrinogen genes has contributed to reveal the molecular mechanisms involved in biosynthesis of the fibrinogen molecule and to clarify the basic processes of fibrin polymerization and fibrinolysis. The compilation of abundant cases with detailed genetic, biological, and clinical features has enabled the classification of congenital fibrinogen disorders into several types and subtypes. Thus, the recent classification of congenital fibrinogen disorder is based not only on the clottable and antigenic fibrinogen levels but also on the patient's clinical phenotype and genotype. Fibrinogen supplementation is the cornerstone of bleeding management in fibrinogen disorders. Since the discovery of blood fractionation, the method of production of fibrinogen concentrate has been progressively modified to significantly improve purity and safety. Nevertheless, the availability of such products is still limited to a few countries and the optimal threshold of fibrinogen to target is still not established. In this review, we describe the major advances that have characterized 100 years of congenital fibrinogen disorders, focusing on afibrinogenemia and dysfibrinogenemia.
先天性纤维蛋白原异常包括广泛的纤维蛋白原缺陷，其特征是广泛的分子和临床谱。自 1920 年首次描述无纤维蛋白血症以来，许多重大成就促进了对这些复杂疾病的更好理解。在所有三个纤维蛋白原基因中发现致病突变有助于揭示纤维蛋白分子生物合成所涉及的分子机制，并阐明纤维蛋白聚合和纤维蛋白溶解的基本过程。大量具有详细遗传、生物学和临床特征的病例的汇编，使先天性纤维蛋白原异常能够分为几种类型和亚型。因此，最近的先天性纤维蛋白原异常分类不仅基于可凝纤维蛋白原和抗原纤维蛋白原水平，还基于患者的临床表型和基因型。纤维蛋白原补充是纤维蛋白原异常出血管理的基石。自血液分离发现以来，纤维蛋白原浓缩物的生产方法不断改进，以显著提高纯度和安全性。然而，此类产品的可用性仍然局限于少数几个国家，目标纤维蛋白原的最佳阈值仍未确定。在这篇综述中，我们描述了 100 年来先天性纤维蛋白原异常的主要进展，重点介绍了无纤维蛋白血症和纤维蛋白原异常血症。
