Heparin resistance in severe thermal injury: a prospective cohort study

Research output: Contribution to journalArticlepeer-review

Standard

Heparin resistance in severe thermal injury : a prospective cohort study. / Cato, Liam; Bailiff, Benjamin; Price, Joshua; Ermogenous, Christos; Hazeldine, Jon; Lester, William; Lowe, Gillian; Wearn, Christopher; Bishop, Jon; Lord, Janet; Moiemen, Naiem; Harrison, Paul.

In: Burns & Trauma, 30.06.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

APA

Vancouver

Author

Bibtex

@article{987c740a7da4469ea1ba2c456b22f3fd,
title = "Heparin resistance in severe thermal injury: a prospective cohort study",
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 hypothesised 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), neutralise LMWH resulting in suboptimal anti-coagulation, assessed by reduction in anti-factor Xa activity. Methods: Blood was sampled from >15% 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. Mixedeffects regression adjusted for multiple confounders, including injury severity and ATIII activity, and was used to test the association between nucleosomes and AFXa. Results: 30 patients with severe burns were included. Mean TBSA 43% (SD 17). 23 (77%) patients were affected by heparin resistance (defined by AFXa activity <0.2IU/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 8000IU 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, wasadjusted 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. Conclusions: Heparin resistance is a prevalent issue in severe burns. Nucleosome levels were increased post-burn, and showed an inverse association with AFXaconsistent 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.",
author = "Liam Cato and Benjamin Bailiff and Joshua Price and Christos Ermogenous and Jon Hazeldine and William Lester and Gillian Lowe and Christopher Wearn and Jon Bishop and Janet Lord and Naiem Moiemen and Paul Harrison",
note = "Not yet published as of 13/10/2021.",
year = "2021",
month = jun,
day = "30",
language = "English",
journal = "Burns & Trauma",
issn = "2321-3868",
publisher = "Springer Verlag",

}

RIS

TY - JOUR

T1 - Heparin resistance in severe thermal injury

T2 - a prospective cohort study

AU - Cato, Liam

AU - Bailiff, Benjamin

AU - Price, Joshua

AU - Ermogenous, Christos

AU - Hazeldine, Jon

AU - Lester, William

AU - Lowe, Gillian

AU - Wearn, Christopher

AU - Bishop, Jon

AU - Lord, Janet

AU - Moiemen, Naiem

AU - Harrison, Paul

N1 - Not yet published as of 13/10/2021.

PY - 2021/6/30

Y1 - 2021/6/30

N2 - 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 hypothesised 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), neutralise LMWH resulting in suboptimal anti-coagulation, assessed by reduction in anti-factor Xa activity. Methods: Blood was sampled from >15% 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. Mixedeffects regression adjusted for multiple confounders, including injury severity and ATIII activity, and was used to test the association between nucleosomes and AFXa. Results: 30 patients with severe burns were included. Mean TBSA 43% (SD 17). 23 (77%) patients were affected by heparin resistance (defined by AFXa activity <0.2IU/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 8000IU 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, wasadjusted 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. Conclusions: Heparin resistance is a prevalent issue in severe burns. Nucleosome levels were increased post-burn, and showed an inverse association with AFXaconsistent 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.

AB - 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 hypothesised 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), neutralise LMWH resulting in suboptimal anti-coagulation, assessed by reduction in anti-factor Xa activity. Methods: Blood was sampled from >15% 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. Mixedeffects regression adjusted for multiple confounders, including injury severity and ATIII activity, and was used to test the association between nucleosomes and AFXa. Results: 30 patients with severe burns were included. Mean TBSA 43% (SD 17). 23 (77%) patients were affected by heparin resistance (defined by AFXa activity <0.2IU/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 8000IU 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, wasadjusted 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. Conclusions: Heparin resistance is a prevalent issue in severe burns. Nucleosome levels were increased post-burn, and showed an inverse association with AFXaconsistent 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.

M3 - Article

JO - Burns & Trauma

JF - Burns & Trauma

SN - 2321-3868

ER -