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Cato LD, Bailiff B, Price J, et al. Heparin resistance in severe thermal injury: A prospective cohort study. Burns Trauma. 2021;9:tkab032doi: 10.1093/burnst/tkab032.
Cato, L. D., Bailiff, B., Price, J., Ermogeneous, C., Hazeldine, J., Lester, W., Lowe, G., Wearn, C., Bishop, J. R. B., Lord, J. M., Moiemen, N., & Harrison, P. (2021). Heparin resistance in severe thermal injury: A prospective cohort study. Burns & trauma, 9tkab032. https://doi.org/10.1093/burnst/tkab032
Cato, Liam D, et al. "Heparin resistance in severe thermal injury: A prospective cohort study." Burns & trauma vol. 9 (2021): tkab032. doi: https://doi.org/10.1093/burnst/tkab032
Cato LD, Bailiff B, Price J, Ermogeneous C, Hazeldine J, Lester W, Lowe G, Wearn C, Bishop JRB, Lord JM, Moiemen N, Harrison P. Heparin resistance in severe thermal injury: A prospective cohort study. Burns Trauma. 2021 Oct 20;9:tkab032. doi: 10.1093/burnst/tkab032. eCollection 2021. PMID: 34692855; PMCID: PMC8528639.
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Burns Trauma. 2021 Oct 20;9:tkab032. doi: 10.1093/burnst/tkab032. eCollection 2021.

Heparin resistance in severe thermal injury: A prospective cohort study.

Burns & trauma

Liam D Cato, Benjamin Bailiff, Joshua Price, Christos Ermogeneous, Jon Hazeldine, William Lester, Gillian Lowe, Christopher Wearn, Jonathan R B Bishop, Janet M Lord, Naiem Moiemen, Paul Harrison

Affiliations

  1. Scar Free Foundation Birmingham Centre for Burns Research, University Hospitals Birmingham Foundation Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2WB, UK.
  2. Department of Haematology, University Hospitals Birmingham Foundation Trust, Mindelsohn Way, Birmingham, B15 2WB, UK.
  3. Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK.
  4. NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham Foundation Trust, Mindelsohn Way, Birmingham, B15 2WB, UK.

PMID: 34692855 PMCID: PMC8528639 DOI: 10.1093/burnst/tkab032

Abstract

BACKGROUND: Low molecular-weight heparin (LMWH) is routinely administered to burn patients for thromboprophylaxis. Some studies have reported heparin resistance, yet the mechanism(s) and prevalence have not been systematically studied. We hypothesized that nucleosomes, composed of histone structures with associated DNA released from injured tissue and activated immune cells in the form of neutrophil extracellular traps (NETs or NETosis), neutralize LMWH resulting in suboptimal anticoagulation, assessed by reduction in anti-factor Xa activity.

METHODS: Blood was sampled from >15% total body surface area (TBSA) burn patients receiving LMWH on days 5, 10 and 14. Peak anti-factor Xa (AFXa) activity, anti-thrombin (ATIII) activity, cell-free DNA (cfDNA) levels and nucleosome levels were measured. Mixed effects regression was adjusted for multiple confounders, including injury severity and ATIII activity, and was used to test the association between nucleosomes and AFXa.

RESULTS: A total of 30 patients with severe burns were included. Mean TBSA 43% (SD 17). Twenty-three (77%) patients were affected by heparin resistance (defined by AFXa activity <0.2 IU/mL). Mean peak AFXa activity across samples was 0.18 IU/mL (SD 0.11). Mean ATIII was 81.9% activity (SD 20.4). Samples taken at higher LWMH doses were found to have significantly increased AFXa activity, though the effect was not observed at all doses, at 8000 IU no samples were heparin resistant. Nucleosome levels were negatively correlated with AFXa (

CONCLUSIONS: Heparin resistance is a prevalent issue in severe burns. Nucleosome levels were increased post-burn, and showed an inverse association with AFXa consistent with the hypothesis that they may interfere with the anticoagulant effect of heparin

© The Author(s) 2021. Published by Oxford University Press.

Keywords: Burn; Enoxaparin; Factor-Xa; Heparin resistance; Low molecular-weight heparin; NETosis; Neutrophil extracellular traps; Nucleosomes; Thrombosis

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