Heparin resistance in severe thermal injury: a prospective cohort study

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

doi:10.1093/burnst/tkab032

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Heparin resistance in severe thermal injury: a prospective cohort study

更新时间：2022-06-14

- Heparin resistance in severe thermal injury: a prospective cohort study
- Heparin resistance in severe thermal injury: a prospective cohort study
- Burns & Trauma 2021年9卷第1期
- 作者机构：
  
  1. Scar Free Foundation Birmingham Centre for Burns Research
  2. University Hospitals Birmingham Foundation Trust
  3. Institute of Inflammation and Ageing
  4. University of Birmingham
  5. Department of Haematology
  6. NIHR Surgical Reconstruction and Microbiology Research Centre
- 作者简介：
- 基金信息：
  
  This work was funded by the Scar Free Foundation and National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, British Society of Haematology and Royal College of Surgeons.
- DOI：10.1093/burnst/tkab032
  中图分类号：
- 纸质出版日期：2021，
  
  网络出版日期：2021-10-20，
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Liam D Cato, Benjamin Bailiff, Joshua Price, 等. Heparin resistance in severe thermal injury: a prospective cohort study[J]. Burns & Trauma, 2021,9(1).

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, Heparin resistance in severe thermal injury: a prospective cohort study, Burns & Trauma, Volume 9, 2021, tkab032, https://doi.org/10.1093/burnst/tkab032
Liam D Cato, Benjamin Bailiff, Joshua Price, 等. Heparin resistance in severe thermal injury: a prospective cohort study[J]. Burns & Trauma, 2021,9(1). DOI： 10.1093/burnst/tkab032.

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, Heparin resistance in severe thermal injury: a prospective cohort study, Burns & Trauma, Volume 9, 2021, tkab032, https://doi.org/10.1093/burnst/tkab032 DOI：

摘要

Abstract

BackgroundLow 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.MethodsBlood 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.ResultsA 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 (r = −0.29

p = 0.050) consistent with the hypothesis. The final model

with peak AFXa as the response variable

was adjusted for nucleosome levels (p = 0.0453)

ATIII activity (p = 0.0053)

LMWH dose pre-sample (p = 0.0049)

drug given (enoxaparin or tinzaparin) (p = 0.03)

and other confounders including severity of injury

age

gender

time point of sample.ConclusionsHeparin 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 in vivo and contribute to heparin resistance. Accurate monitoring of AFXa activity with appropriate therapy escalation plans are recommended with dose adjustment following severe burn injury.

关键词

Keywords

BurnHeparin resistanceLow molecular-weight heparinNucleosomesNeutrophil extracellular trapsFactor-XaThrombosisEnoxaparinNETosis

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