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| 1 | Heparin resistance in severe thermal injury:a prospective cohort study显示文摘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,cellfree 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).Twentythree(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.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 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. | Liam D Cato Benjamin Bailiff Joshua Price Christos Ermogeneous Jon Hazeldine William Lester Gillian Lowe Christopher Wearn Jonathan RB Bishop Janet M Lord Naiem Moiemen Paul Harrison | 2021 | Burns & Trauma2021，9，1： | 3 |
| 2 | Retrograde intubation dacryocystorhinostomy for proximal and midcanalicular obstruction显示文摘 | Wearne MJ Beiji B Davis G | 1999 | Ophthalmology1999，106，12： | 1 |
| 3 | The nature of the vascular communications between the coronary arteries and the chambers of the heart显示文摘 | Wearn JT Mettier SR Klumpp TG | 1933 | Am Heart J1933，9，： | 1 |
| 4 | Automated algorithms for multiscale morphometry of neuronal dendrites显示文摘 | WEAVER C M HOF P R WEARNE S L | 2004 | Neural Gomput2004，16，17： | 1 |
| 5 | Fractional reaction-diffusion显示文摘 | Henry B I Wearne S L | 2000 | Physica A2000，276，3： | 1 |
| 6 | Pharmacokinetics of pioglitazone after multiple oral dose administration in homes显示文摘 | Wearn JM Crisman MV Davis JL Geor R J Hodgson DR Suagee JK | 2011 | Vet Pharmacol Ther2011，4，3： | 1 |
| 7 | Determination of important pulp properties of hybrid poplar by near infrared spectroscopy显示文摘 | Schiraleck L R Payne P Wearne R H | 2005 | Wood and Fiber Science2005，37，3： | 1 |
| 8 | An online course in clinical education-Experiences of Australian clinicians显示文摘 | Wearne S G-reenhill J Berryman C | 2011 | Aust Fam Physician2011，40，12： | 1 |
| 9 | Fractional reaction-diffusion显示文摘 | HENRY B I WEARNE S L | 2000 | Physica A2000，276，： | 1 |
| 10 | Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys 显示文摘 | Duan H Wearne S L Rocher A B | 2003 | Cereb Cortex2003，13，9： | 1 |
| 11 | Coronary Heart Disease Incidence and Cardiovascular Mortality in Busselton with Reference to Glucose and Insulin Concentrations显示文摘 | Welborn T A Wearne K | 1979 | Diabetes Care1979，2，2： | 1 |
| 12 | Fractional reaction-diffusion显示文摘 | Henry B I Wearne S L | 2000 | Physica A: Statistical Mechanics and its Applications2000，276，34： | 1 |
| 13 | Fractionation on the polymeric components of hardwoods by autohydrolysis-explosion-extraction显示文摘 | WALLIS A WEARNE R H | 1985 | Appita J1985，38，6： | 1 |
| 14 | Clinical and Radiological Outcomes of Minimally Invasive Versus Open Transforaminal Lumbar Interbody Fusion显示文摘 | Chan Wearn Benedict Peng Wai Mun Yue Seng Yew Poh William Yeo Seang Beng Tan | 2009 | Spine2009，，13： | 1 |
| 15 | Fractional cable equation models for anomalous electrodiffusion in nerve cells: infinite domain solutions 显示文摘 | LANGLANDS T A M HENRY B I WEARNE S L | 2009 | J Math Biol2009，59，6： | 1 |
| 16 | Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations显示文摘 | Welborn TA Wearne K | 1979 | Diabetes Care1979，2，： | 1 |
| 17 | Pefioperative antibiotic prophylaxisduring phaco-emulsification and intraocular lensimplantation: national survey of smaller eye units in England显示文摘 | NanavatyMA Wearne MJ | 2010 | Clin Expertment Oph- thalmol2010，38，5： | 1 |
| 18 | Species and Organ Specificity of Fungal Endophytesin Herbaceous Grassland Plants显示文摘 | Wearn J A Sutton B C Morley N J | 2012 | Journal of Ecology2012，100，5： | 1 |
| 19 | Fractional cable equation models for anomalous electrodi, usion in nerve cells: infinite domain solutions显示文摘 | LANGLANDS T A M HENRY B I WEARNE S L | 2009 | Journal of Mathematical Biology2009，59，6： | 1 |
| 20 | Pharmacokinetics of pioglitazone after multiple oral dose administration in horses 显示文摘 | WEARN J M G CRISMAN M V DAVIS J L | 2011 | J Vet Pharmacol Therap2011，34，3： | 1 |
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