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    Poster Networking

    Hemophilia and Rare Bleeding Disorders

    Poster Networking Session

    PB0209 - Clinical manifestations of patients with congenital dysfibrinogenemia with the most common hotspot mutation in FGA gene p.Arg35His

    Sunday, June 25, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      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)

    • 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

    • Jana Zolkova, DSc, PhD (she/her/hers)

      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

    • ZK

      Zuzana Kolkova

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

    • DL

      Dusan Loderer

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

    • Ingrid Skornova, Ing.

      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

    • Jan Stasko, MD, PhD (he/him/his)

      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 dysfibrinogenemia is a rare coagulation disorder characterized by normal fibrinogen antigen levels associated with low functional activity. The majority of cases are caused by heterozygous missense mutations in one of the three fibrinogen genes. The most common hotspot mutation responsible for dysfibrinogenemia is mutation in exon 2 FGA gene p.Arg35His which is a part of the thrombin cleavage site in the fibrinogen Aα chain. Hotspot mutations have been reported with highly heterogeneous of clinical presentation, including bleeding and thrombosis.

    Aims: The aim of this monocentric study of 58 dysfibrinogenemic patients with heterozygous hotspot mutation in FGA gene p.Arg35His was to characterize the incidence of bleeding and thrombotic events.

    Methods: The clinical phenotype was assesed by the ISTH bleeding assessment tool (BAT). Fibrinogen was measured including the Clauss assay and immunologic methods. The coagulation was assessed prothrombin time (PT), activated partial thromboplastin time (APTT), reptilase time (RT), and thrombin time (TT). FGA gene was analyzed using polymerase chain reaction (PCR) amplification followed by sequencing.

    Results: The clinical phenotype consisted of bleeding in 16/58 (27.5%) patients; thrombosis in 4/58 (7.0%) patients. Bleeding but also thrombosis were observed in 3/58 (5.2%). In 35/58 (60.3%) patients was an asymptomatic phenotype. BAT in a group of bleeding patients was ranged 1 - 4, most often presented by epistaxis, bruising and menorrhagia.

    Conclusion(s): The majority of dysfibrinogenemic patients in our cohort with hotspot mutation of p.Arg35His were asymptomatic, but almost 1/3 of patients have bleeding diathesis, in a few cases very severe. Our results of clinical phenotypes are consistent with previous published studies, reporting that according to which mutations near the binding sites of thrombin are usually asymptomatic.