PB0714 - Genetic and clinical characterization in 106 patients with congenital quantitative and qualitative fibrinogen deficiencies: a Slovak centre experience

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Tomas Simurda, MD, PhD.

physician
National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Slovakia
Martin, Zilina, Slovakia

Co-Author(s)

Jana Zolkova, DSc, PhD

laboratory researcher
National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Slovakia
Martin, Zilina, Slovakia
Miroslava Drotarova, MD

PhD. student
National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Slovakia
Martin, Zilina, Slovakia
ZK

Zuzana Kolkova

researcher
Biomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia
Martin, Zilina, Slovakia
DL

Dusan Loderer

Laboratory diagnostician
Biomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin
Martin, Zilina, Slovakia
MD

Miroslava Dobrotová

physician-hematologist
National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
Martin, Zilina, Slovakia
IP

Ivana Plameňová

physician - hematologist
Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Depatment of Hematology and Transfusion medicine, University Hospital in Martin, National Center of Hemostasis and Thrombosis, Slovak Republic
Martin, Zilina, Slovakia
PH

Pavol Holly

physician
National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Slovakia
Martin, Zilina, Slovakia
JH

Jan Hudecek

physician
National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Slovakia
Martin, Zilina, Slovakia
IS

Ingrid Skornova

Laboratory diagnostician
National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
Martin, Zilina, Slovakia
Monika Brunclikova, MD

physician
National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Slovakia
Martin, Zilina, Slovakia
MG

Marian Grendar

biostatistician
Biomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin
Martin, Zilina, Slovakia
ZL

Zora Lasabova

university teacher
Department of Molecular Biology and Genomics, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin
Martin, Zilina, Slovakia
JS

Jan Stasko

university professor
National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
Martin, Zilina, Slovakia
PK

Peter Kubisz

university professor
National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusion Medicine, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Martin, Slovakia
Martin, Zilina, Slovakia

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.