PB1198 - Retrospective Genotypic Data Analysis of Patients with Suspected Hereditary Fibrinogen Deficiency

Background: Fibrinogen plays an important role in primary and secondary hemostasis.
Mutations affecting the fibrinogen genes (FGA, FGB, and FGG) result in either quantitative (afibrinogenaemia, hypofibrinogenaemia) or qualitative (dysfibrinogenaemia, hypodysfibrinogenemia) deficiencies.

Aims: The aim of this study was to perform a retrospective genotypic data analysis of patients with suspected hereditary fibrinogen deficiency from the Institute of Experimental Haematology and Transfusion Medicine (University Clinic Bonn, Germany) between 2011 and 2020.

Methods: Direct fibrinogen mutation screening was performed either with an Applied Biosystems (ABI) sequencer (pre-2017) or via Next-Generation Sequencing (NGS, Nextra Flex, 2017 and later). Clinical and laboratory data including fibrinogen values were collected in local laboratories prior to genotyping.

Results: 683 patients were included for analysis, of which 409 were female and 274 were male (median age: 28.3 years; range 1-86 years). In 377 (55 %) patients, potentially causative mutations within the fibrinogen genes (FGA, FGB, or FGG) were detected, whereas in the remaining 306 (45 %) no mutations were found, suggesting other reasons for deficiency. Among the patients with confirmed hereditary fibrinogen deficiency (n=377), 235 (62.3 %) had hypofibrinogenemia, 125 (33.2 %) had dysfibrinogenemia or hypodysfibrinogenemia, 12 (3.2 %) had afibrinogenemia, and in five (1.3 %) patients the type of fibrinogen deficiency remained unknown (incomplete phenotypic data). The p. Ala108Gly (γAla82Gly) variant in FGG gene was the most common variant causing hypofibrinogenemia (n=91, 38.7 %). The p. Arg35Cys and p. Arg35His variants in the FGA gene and p. Arg301Cys and p. Arg301His variants in the FGG gene were the most common mutations causing dysfibrinogenemia. Furthermore, a large number of novel and previously described variants were identified.

Conclusion(s): Our retrospective data analysis revealed pathogenic or potentially pathogenic mutations in 55 % of cases while in the remaining patients, no mutations have been identified, suggesting other reasons for fibrinogen deficiency.