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    Poster Networking

    Coagulation and Natural Anticoagulants

    Poster Networking Session

    PB1076 - Congenital protein C deficiency is associated with prothrombotic plasma fibrin clot phenotype

    Tuesday, June 27, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      Co-Author(s)

    • AW

      Anna Weronska

      Student
      Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland
      Krakow, Malopolskie, Poland

    • MZ

      Michał Ząbczyk, PhD

      Researcher, Assistant Professor
      Jagiellonian University Medical College
      Krakow, Malopolskie, Poland

    • PM

      Pilar Medina

      PI
      Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain
      Valencia, Comunidad Valenciana, Spain

    • AK

      Adrianna Klajmon

      Student
      John Paul II Hospital
      Krakow, Malopolskie, Poland

      • Presenting Author(s)

    • Anetta Undas, MD PhD

      Professor
      Department of Thromboembolic Diseases, Institute of Cardiology, Jagiellonian University Medical College, Krakow
      Krakow, Malopolskie, Poland

      • Co-Author(s)

    • EW

      Ewa Wypasek

      Head of Molecular Biology Laboratory
      John Paul II Hospital
      Krakow, Malopolskie, Poland

    Background: Congenital protein C (PC) deficiency is an inherited thrombophilia with a prevalence of 0.2% to 0.4% in the general population and 3% in unselected venous thromboembolic patients. In most individuals PC deficiency is caused by heterozygous mutations in PROC gene.

    Aims: We hypothesized that congenital PC deficiency affects fibrin clot structure and function.

    Methods: Twenty-two patients (aged 34 [18-66] years; 36% women), 12 after venous thromboembolism (VTE) and 10 asymptomatic with a positive family history of VTE, were screened for PROC mutations by sequencing 9 PROC exons and their flanking intron regions. Plasma fibrin clot permeability (Ks), clot lysis time (CLT), along with thrombin generation parameters, including endogenous thrombin potential (ETP) and plasminogen activator inhibitor 1 (PAI-1) antigen were assessed and compared to 22 age- and sex-matched healthy controls.

    Results: The mean (SD) PC activity in PC-deficient patients assessed by a chromogenic assay was 57.0% (8.6%), by a clot-based assay was 52.6% (11.2%) and the antigen levels were 63.4% (26.0%). Fifteen probands (67%) had missense mutations, five patients (22%) carried nonsense variants, and the other two subjects (11%) had splice-site mutations.
    Despite similar fibrinogen concentrations in the patient and control groups, PC deficiency was associated with 20% lower Ks (p=0.04) and 35% longer CLT (p=0.002), along with 35% higher ETP and 60% higher peak thrombin generated as well as 300% higher PAI-1 (all p< 0.01). There were no differences related to the type of PROC mutations or the VTE status (yes/no) in those variables. Ks was inversely associated with PC antigen while CLT was positively associated with PC antigen and PAI-1 levels (all p=0.05), but not PC activities.

    Conclusion(s): Our ongoing study suggests that congenital PC deficiency is associated with the prothrombotic plasma fibrin clot phenotype. Molecular background for this funding in PC-deficient patients remains to be established.