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Updated: Oct 3, 2025
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Heparin-Functionalized Adsorbents Eliminate Central Effectors of Immunothrombosis, including Platelet Factor 4,
Marie Ebeyer-Masotta1, Tanja Eichhorn1, René Weiss1
1Center for Biomedical Technology, Department for Biomedical Research, Danube University Krems, 3500 Krems, Austria.
Insights
Heparin-functionalized adsorbents can remove key drivers of inflammation and thrombosis, such as activated platelets and neutrophil extracellular traps (NETs). This approach may help treat thrombotic complications in sepsis and COVID-19.
Area of Science:
- Biomedical Engineering
- Immunology
- Hematology
Background:
- Inflammation and thrombosis are linked in critical illnesses like sepsis and COVID-19.
- Thrombotic complications indicate severe disease, leading to organ failure and death.
- Immunothrombosis involves the complement/tissue factor/neutrophil axis, activated platelets, and neutrophil extracellular traps (NETs).
Purpose of the Study:
- To investigate the potential of heparin-functionalized adsorbents in mitigating immunothrombosis.
- To evaluate the capacity of these adsorbents to deplete key effectors of immunothrombosis.
Main Methods:
- Utilized adsorbents functionalized with endpoint-attached heparin.
- Assessed the depletion of activated platelets, platelet-derived extracellular vesicles (pEVs), platelet factor 4 (PF4), high-mobility box 1 protein (HMGB1), histones, and nucleosomes.
Main Results:
- Heparin-functionalized adsorbents efficiently depleted activated platelets, pEVs, PF4, HMGB1, histones, and nucleosomes.
- These depleted factors are central effectors of deregulated immunothrombosis.
Conclusions:
- Heparin-functionalized adsorbents can eliminate key drivers of immunothrombosis.
- This depletion mechanism, rather than direct pathogen binding, may be clinically relevant for managing thrombosis in sepsis and COVID-19.
Abstract:
Inflammation and thrombosis are closely intertwined in numerous disorders, including ischemic events and sepsis, as well as coronavirus disease 2019 (COVID-19). Thrombotic complications are markers of disease severity in both sepsis and COVID-19 and are associated with multiorgan failure and increased mortality. Immunothrombosis is driven by the complement/tissue factor/neutrophil axis, as well as by activated platelets, which can trigger the release of neutrophil extracellular traps (NETs) and release further effectors of immunothrombosis, including platelet factor 4 (PF4/CXCL4) and high-mobility box 1 protein (HMGB1). Many of the central effectors of deregulated immunothrombosis, including activated platelets and platelet-derived extracellular vesicles (pEVs) expressing PF4, soluble PF4, HMGB1, histones, as well as histone-decorated NETs, are positively charged and thus bind to heparin. Here, we provide evidence that adsorbents functionalized with endpoint-attached heparin efficiently deplete activated platelets, pEVs, PF4, HMGB1 and histones/nucleosomes. We propose that this elimination of central effectors of immunothrombosis, rather than direct binding of pathogens, could be of clinical relevance for mitigating thrombotic complications in sepsis or COVID-19 using heparin-functionalized adsorbents.
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