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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 | Control strategies for aeroallergens in an animal facility显示文摘 | Reeb-Whitaker CK Harrison DJ Jones RB | 1999 | J Allergy Clin immunol1999，103，： | 1 |
| 3 | Computed tomography for metastatic lesions of the osseous pelvis显示文摘 | Patel RB Harrison RB | 1983 | South Med J1983，76，12： | 1 |
| 4 | Intuhating conditions and hemodynamic effects of etomidate for rapid sequence intubation in the emergency department:an observational cohortstudy显示文摘 | Zed PJ Abu-Laban RB Harrison DW | 2006 | Acad Emerg Med2006，13，： | 1 |
| 5 | Intubating conditions and hemodynamic effects of etomidate for rapid sequence intubation in the emergency department: an observational cohort study显示文摘 | Zed PJ Abu-Laban RB Harrison DW | 2006 | Acad Emerg Med2006，13，4： | 1 |
| 6 | Intubating conditions and hemodynamic effects of etomidate for rapid sequence intubation in the emergency department:an observational cohort study 显示文摘 | Zed PJ Abu-Laban RB Harrison DW | 2006 | Acad Emerg Med2006，13，4： | 1 |
| 7 | Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5显示文摘 | Vega RB Harrison BC Meadows E | 2004 | Mol Cell Biol2004，24，： | 1 |
| 8 | Growth differentiation factor 9 is a germ cell regulator of sertoli cell function显示文摘 | Nicholls PK Harrison CA Gilchrist RB | 2009 | Endocrinology2009，150，5： | 1 |
| 9 | Mammary development, carcinomas and progesterone: role of Wnt signalling显示文摘 | Lamb R Harrison H Clarke RB | 2007 | Ernst Schering Found Symp Proc2007，，1： | 1 |
| 10 | Computed tomography for metastic lesions of the osseous pelivis 显示文摘 | patel RB Harrison RB | 1983 | South Med J1983，76，12： | 1 |
| 11 | Mammary development,carcinomas and progesterone:role of Wnt signaling显示文摘 | Lamb R Harrison H Clarke RB | 2007 | Ernst Schering Found Symp Proc2007，，1： | 1 |
| 12 | Forest soils edu- cation and research: Trends, needs, and wild ideas显示文摘 | FISHER RF FOX TR HARRISON RB TERRY T | 2005 | Forest Ecology and Management2005，220，： | 1 |
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