Abstract Number: PB0714
Meeting: ISTH 2022 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Rare Bleeding Disorders
Background: Congenital fibrinogen disorders (CFD) are considered as rare disorders of hemostasis. In afibrinogenemia and hypofibrinogenemia, most mutations of the FGA, FGB, or FGG fibrinogen encoding genes are null mutations. Dysfibrinogenemia is caused mainly by missense mutations. Patients with CFD are usually associated with bleeding phenotype or thrombosis, but many of them are asymptomatic. Aim of the study was to characterize the clinical manifestations and genetic background in patients with CFD presenting at our centre.
Aims: To identify genetic basis and associated clinical and laboratory phenotypes in cross-sectional survey of 106 patients from 53 unrelated families with congenital fibrinogen disorder using basic laboratory screening tests and genetic analysis of FGA, FGB, and FGG genes.
Methods: In 106 patients from 53 unrelated families (mean [SD] age, 38 [18.8] years; 28.0% men) there were realized standard coagulation tests, fibrinogen activity and antigen (Clauss method, LIA). Genetic analysis of all three fibrinogen genes was performed by high-throughput sequencing with confirmation of mutations by Sanger sequencing method.
Results: The clinical phenotype consisted of bleeding in 32/106 (30.2%), thrombotic events 14/106 (13.2%) patients, additional other patients were asymptomatic. The following CFD were identified: 1A afibrinogenemia, n = 1; 2A severe hypofibrinogenemia, n = 3; moderate hypofibrinogenemia, n = 1; 2C mild hypofibrinogenemia, n = 20; 3A dysfibrinogenemia, n = 80; 4C mild hypodysfibrinogenemia, n = 1. Hotspot mutations in FGA (exon 2) were identified in 64 dysfibrinogenemic patients. In other patients there were identified 1 mutation in FGA, 7 mutations in FGB and 10 mutations in FGG gene.
Conclusion(s): In our cross-sectional study there were 56.6% asymptomatic patients with CFD. The remainder of the patients with CFD had either bleeding or thrombosis. Clinical manifestations showed similar features irrespective of genotype. Nevertheless, results from genetic and clinical studies seems to yield valuable information on the structure and function of the fibrinogen molecule.
To cite this abstract in AMA style:
Simurda T, Zolkova J, Sterankova M, Kolkova Z, Loderer D, Dobrotova M, Plamenova I, Holly P, Hudecek J, Skornova I, Brunclikova M, Grendar M, Lasabova Z, Stasko J, Kubisz P. Genetic and clinical characterization in 106 patients with congenital quantitative and qualitative fibrinogen deficiencies: a Slovak centre experience [abstract]. https://abstracts.isth.org/abstract/genetic-and-clinical-characterization-in-106-patients-with-congenital-quantitative-and-qualitative-fibrinogen-deficiencies-a-slovak-centre-experience/. Accessed October 1, 2023.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/genetic-and-clinical-characterization-in-106-patients-with-congenital-quantitative-and-qualitative-fibrinogen-deficiencies-a-slovak-centre-experience/