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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 | A genetic linkage map for cattle显示文摘 | Michael D Bishop Steven M | 1994 | Genetics1994，136，： | 2 |
| 3 | A genetic linkage map for cattle 显示文摘 | Bishop M D Kappes S M | 1994 | Genetics1994，136，： | 1 |
| 4 | Chilling sensitivity in higher plants:The role of phosphatidylglycerol显示文摘 | Bishop D G | 1986 | Plant Cell & Environment1986，9，8： | 1 |
| 5 | An Investigation into the Theory of Resonance Testing显示文摘 | Bishop R E D Gladwell G M L | 1963 | Phil Trans1963，225，22： | 1 |
| 6 | Enhanced deposition of predominantly typeI collagen in myocardial disease显示文摘 | Bishop J E Greenbaum R Gibsonj D G | 1990 | J Mel Cell Cardiol1990，22，10： | 1 |
| 7 | Activities of three digestive enzymes during development in the crayfish Procambarus clarkii (Decapoda) 显示文摘 | Hammer H S Bishop C D Watts S A | 2000 | J Crustac Biol2000，20，： | 1 |
| 8 | The Fifth Annual Fairley Lecture on the Linear Representation of Fluid Forces and Movements in Unsteady Flow显示文摘 | Bishop R E D Burcher R K Price W G | 1973 | Journal of Sound and Vibration1973，29，1： | 1 |
| 9 | Virus taxonomy, 6th Report of the International Committee on Taxonomy of Viruses (ICTV) 显示文摘 | Murphy F A Fauquet C M Bishop D H L | 1995 | Arch Virol1995，10，： | 1 |
| 10 | Peroxisome proliferator-activated receptors in the cardiovascular system显示文摘 | Bishop Bailey D | 2000 | Bri J Pharmacol2000，129，： | 1 |
| 11 | Remote sensing and geomorphometry for studying relief production in high mountains显示文摘 | Michael P Bishop John F Shroder Jr Jeffrey D Colby | 2003 | Geomorphology2003，55，： | 1 |
| 12 | Heparan sulphate proteoglycans fine- tune mammalian physiology显示文摘 | Bishop J R Schuksz M Esko J D | 2007 | Natute2007，446，7139： | 1 |
| 13 | Mid-IR focal plane array based on type-ⅡIn As/Ga Sb strain layer superlattice detector with n Bn design显示文摘 | Kim H S Plis E Bishop G D | 2008 | Applied Physics Letters2008，92，： | 1 |
| 14 | Athletic footwear,leg stiffness,and running kinematics显示文摘 | Bishop M Fiolkowski P Conrad B Brunt D Horodyski M | | 0，，： | 1 |
| 15 | Prediction of scenic beauty using mapped data and geographic information systems显示文摘 | Bishop I D Hulse D W | | 0，，： | 1 |
| 16 | Linking gisbased models to value ecosystem services in an alpine region显示文摘 | GRêT-REGAMEY A BEBI P BISHOP I D | 2008 | Journal of Environmental Management2008，89，3： | 1 |
| 17 | The McMaster Family As- sessment Device显示文摘 | Epstein N Baldwin L Bishop D | 1983 | J Marital Fam Ther1983，9，2： | 1 |
| 18 | Nonlinear response theory with relaxation: the first-order hyperpolarizability 显示文摘 | Normana P Bishop D M Jensen H J A | 2005 | Chemical Physics2005，123，19： | 1 |
| 19 | Cell division and cell survival in theabsence of Survivin显示文摘 | Yang D Welm A Bishop J M | 2004 | Proc Natl Acad Sci USA2004，101，15： | 1 |
| 20 | Vitrous phenotype:genotype correlation in Stickler syndrome显示文摘 | Mcleod D Black G Bishop PN | 2002 | Graefe Arch Clin Exp Ophthalmol2002，240，： | 1 |
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