Brunclikova Monika, Simurda Tomas, Zolkova Jana, Sterankova Miroslava, Skornova Ingrid, Dobrotova Miroslava, Kolkova Zuzana, Loderer Dusan, Grendar Marian, Hudecek Jan, Stasko Jan, Kubisz Peter
National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia.
Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia.
J Clin Med. 2022 Feb 18;11(4):1083. doi: 10.3390/jcm11041083.
Congenital fibrinogen disorders are diseases associated with a bleeding tendency; however, there are also reports of thrombotic events. Fibrinogen plays a role in the pathogenesis of thrombosis due to altered plasma concentrations or modifications to fibrinogen's structural properties, which affect clot permeability, resistance to lysis, and its stiffness. Several distinct types of genetic change and pathogenetic mechanism have been described in patients with bleeding and a thrombotic phenotype, including mutations affecting synthesis or processing in three fibrinogen genes. In this paper, we focused on familial hypofibrinogenemia, a rare inherited quantitative fibrinogen disorder characterized by decreased fibrinogen levels with a high phenotypic heterogeneity. To begin, we briefly review the basic information regarding fibrinogen's structure, its function, and the clinical consequences of low fibrinogen levels. Thereafter, we introduce 15 case reports with various gene mutations derived from the fibrinogen mutation database GFHT (French Study Group on Hemostasis and Thrombosis), which are associated with congenital hypofibrinogenemia with both bleeding and thrombosis. Predicting clinical presentations based on genotype data is difficult. Genotype-phenotype correlations would be of help to better understand the pathologic properties of this rare disease and to provide a valuable tool for the identification of patients who are not only at risk of bleeding, but also at risk of a thrombotic event.
先天性纤维蛋白原异常是与出血倾向相关的疾病；然而，也有血栓形成事件的报道。由于血浆浓度改变或纤维蛋白原结构特性的改变，纤维蛋白原在血栓形成的发病机制中起作用，这会影响凝块的通透性、对溶解的抵抗力及其硬度。在有出血和血栓形成表型的患者中，已经描述了几种不同类型的基因变化和发病机制，包括影响三个纤维蛋白原基因合成或加工的突变。在本文中，我们重点关注家族性低纤维蛋白原血症，这是一种罕见的遗传性纤维蛋白原定量异常疾病，其特征是纤维蛋白原水平降低且表型异质性高。首先，我们简要回顾一下关于纤维蛋白原结构、其功能以及低纤维蛋白原水平的临床后果的基本信息。此后，我们介绍了来自纤维蛋白原突变数据库GFHT（法国止血与血栓形成研究组）的15例具有各种基因突变的病例报告，这些病例与伴有出血和血栓形成的先天性低纤维蛋白原血症相关。基于基因型数据预测临床表现很困难。基因型-表型相关性将有助于更好地理解这种罕见疾病的病理特性，并为识别不仅有出血风险而且有血栓形成事件风险的患者提供有价值的工具。
