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Poster Networking

Vascular Biology, Blood Cells, and Immunothrombosis

PB0850 - Tocilizumab Reduces Hypercoagulation in COVID-19 - Perspectives from The Coagulation and Immunomodulation Covid Assessment Clinical Trial.

Monday, June 24, 2024
13:45 – 14:45 ICT
Room: Exhibition Hall

    Co-Author(s)

  • LA

    Lou Almskog

    MD, PhD student
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • AS

    Anna Sjöström

    MD, PhD
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • JS

    Jonas Sundén-Cullberg

    MD, PhD
    Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • AÃ

    Anna Ã…gren

    MD, PhD
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • SF

    Sara Freyland

    Biostatistician
    Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • AT

    Apostolos Taxiarchis

    PhD
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • MB

    Madeleine Börjesson

    MD
    Karolinska University Hospita, Huddinge, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • AW

    Agneta Wikman

    MD, Professor
    Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, Sweden
    Stockholm, Stockholms Lan, Sweden

  • CW

    Carl Magnus Wahlgren

    MD, Professor
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • MW

    Michael Wanecek

    MD, PhD
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • Jv

    Jan van der Linden

    MD, Professor
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

  • JA

    Jovan Antovic

    MD, Professor
    Coagulation, Clinical Chemistry, Department Molecular Medicine & Surgery, Karolinska Institute & Clinical Chemistry & 24/7, Medical Diagnostics Karolinska, Karolinska University Hospital Stockholm Sweden
    Stockholm, Stockholms Lan, Sweden

  • JL

    Jon Lampa

    MD, Professor
    Department of Medicine, Rheumatology Unit, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden
    Stockholm, Stockholms Lan, Sweden

    • Presenting Author(s)

  • Maria Magnusson, MD, PhD

    Acting head of Department of Hematology,
    Karolinska University Hospital, Karolinska Institutet
    Stockholm, Stockholms Lan, Sweden

Background: Despite medical interventions, COVID-19 persists as a pandemic. Hypercoagulation is prevalent in severe cases, leading to an elevated incidence of thromboembolic events. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood.

Aims: Our objective was to assess whether interleukin inhibitors anakinra or tocilizumab, when administered alongside standard care to patients with severe COVID-19, exhibit significant effects on global hemostasis tests and conventional coagulation laboratory tests, indicative of reduced hypercoagulation patterns compared to standard care alone.

Methods: 74 hospitalized patients with COVID-19 were randomized to receive either anakinra or tocilizumab in addition to standard care, or standard care alone. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential. Secondary outcomes included effects on conventional coagulation laboratory tests.

Results: In the tociluzumab group, ROTEM variables exhibited less hypercoagulation after 29 days compared to anakinra or standard care treatment groups, characterized by increased clot formation time (p < 0.001) and decreased clot firmness (p < 0.001, EXTEM-MCF, Figure 1). Overall Coagulation Potential and Overall Hemostatic Potential decreased, while Overall Fibrinolytic Potential increased over time, with no significant differences between treatments. P-fibrinogen levels, initially elevated, decreased significantly in tocilizumab recipients over time (p=0.004, P-fibrinogen, Figure 2).

Conclusion(s): Tocilizumab demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, as evidenced by improvements in both ROTEM and P-fibrinogen, in comparison to anakinra or standard care alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to positively impact thrombosis incidence.