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Poster Networking

Modulators of Coagulation and von Willebrand Factor

PB0319 - Reduced plasma selenoprotein P is associated with type I antithrombin deficiency and prothrombotic clot phenotype

Sunday, June 23, 2024
13:45 – 14:45 ICT
Room: Exhibition Hall

    Co-Author(s)

  • MK

    Magdalena Kopytek

    PhD, Assistant
    Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland
    Krakow, Malopolskie, Poland

    • Co-Author(s)

  • Javier Corral

    Professor
    Servicio de Hematología, Hospital General Universitario Morales Messeguer, Centro Regional de Hemodonación, Universidad de Murcia, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-ISCIII
    Murcia, Murcia, Spain

  • María Eugenia de la Morena-Barrio, PhD

    PhD
    Servicio de Hematología, Hospital General Universitario Morales Messeguer, Centro Regional de Hemodonación, Universidad de Murcia, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-ISCIII
    Murcia, Murcia, Spain

  • CB

    Carlos Bravo-Pérez

    PhD MD
    Servicio de Hematología, Hospital General Universitario Morales Messeguer, Centro Regional de Hemodonación, Universidad de Murcia, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-ISCIII
    Murcia, Murcia, Spain

  • AK

    Adrianna Klajmon

    Assistant
    Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland
    Krakow, Malopolskie, Poland

  • JN

    Joanna Natorska

    Professor
    Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland
    Krakow, Malopolskie, Poland

  • UJ

    Urszula Jankowska

    PhD, Core Facility Leader
    Malopolska Centre of Biotechnology (MCB), Jagiellonian University, Krakow, Poland
    Krakow, Malopolskie, Poland

  • BS

    Bożena Skupien-Rabian

    PhD, Technician
    Malopolska Centre of Biotechnology (MCB), Jagiellonian University, Krakow, Poland
    Krakow, Malopolskie, Poland

  • JT

    Jacek Treliński

    Department of Haemostasis Disorders
    Medical University of Lodz
    Łódź, Lodzkie, Poland

    • Presenting Author(s)

  • Anetta Undas, MD, PhD

    Professor
    Krakow Centre for Medical Research and Technologies, Saint John Paul II Hospital, Kraków, Poland, Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland
    Krakow, Malopolskie, Poland

    • Co-Author(s)

  • MZ

    Michał Ząbczyk

    Professor
    Krakow Centre for Medical Research and Technologies, John Paul II Hospital, Kraków, Poland
    Krakow, Malopolskie, Poland

Background: A positive association between antithrombin (AT) and selenium level was reported. Selenoprotein P (SEPP), as the most important selenium carrier, was identified within human plasma fibrin clots.

Aims: To investigate the relationship between SEPP and AT and its role in fibrin clot properties modulation in AT-deficient patients.

Methods: In 100 patients with genetically confirmed type I (62%) or IIb (Heparin Binding Site defects, 38%) AT deficiency and in age-matched healthy controls (n=25), endogenous thrombin potential (ETP), fibrin clot permeability (Ks), clot lysis time (CLT) using the assays established by Pieters (CLT-2018) and by Lisman (CLT-2001) were assessed. Proteomics of plasma fibrin clots was performed using mass spectrometry. Plasma SEPP, active factor VII–AT complex (FVIIa-AT) and prothrombin fragments 1+2 (F1+2) levels were evaluated by ELISAs. The Ethical Committee approved the study and all participants provided written informed consent in accordance with the Declaration of Helsinki.

Results: Type I compared to type IIb AT-deficient patients and controls had about 40% reduced plasma SEPP levels (Fig. 1B), associated with AT antigen (r=0.38, p=0.0001) but not activity. Patients with type I compared to type IIb AT deficiency had 5.2-fold increased clot-bound levels of AT and 2.7-fold higher clot-bound amounts of SEPP (Fig. 1A). Type I compared to type IIb AT deficiency was associated with lower FXa activity (-12%), AT antigen (-34.8%), along with higher ETP (+35.8%, Fig. 1C), reduced Ks (-13%), prolonged CLT-2001 (+24.2%), and CLT-2018 (+12.2%) (all p< 0.01). No intergroup differences were found in fibrinogen, FVIIa-AT or F1+2. Plasma SEPP correlated with ETP (r=-0.32, p=0.0015), Ks (Fig. 1D), CLT-2001 (r=-0.36, p=0.006), and CLT-2018 (Fig. 1E) in AT-deficient patients.

Conclusion(s): Reduced plasma SEPP levels observed in type I AT-deficient patients are associated with increased clot-bound SEPP and prothrombotic fibrin clot phenotype as well as thrombin generation. This work was supported by the Polish National Science Centre (UMO-2018/31/D/NZ5/01299).