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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 | Photopolymerizationkinetics and structure development of templated lyotropic liquidcrystalline systems显示文摘 | LESTER C L COLSON C D GUYMON C A | 2001 | Macromolecules2001，34，13： | 1 |
| 3 | Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21 显示文摘 | Nicolae D Cox NJ Lester LA | 2005 | Am J Hum Genet2005，76，2： | 1 |
| 4 | Cloning and expression of cytochrome P450 genes controlling flower colour显示文摘 | Holton T Brugliera F Lester D R | 1993 | Nature1993，366，18： | 1 |
| 5 | Polybrominated diphenyl ether (PBDE) flame retardants显示文摘 | Frank Rahman Katherine H Langford Mark D Scrimshaw John N Lester | 2001 | Science of the Total Environment2001，，1： | 1 |
| 6 | Membership in fraternities and so- rorities, depression, and suicidal ideation 显示文摘 | Ridgway R Tang C Lester D | 2014 | Psychol Rep2014，114，3： | 1 |
| 7 | Initial public offering investor valuations: an examination of top management team prestige and environmental uncertainty 显示文摘 | Lester R H Certo S T Dalton C M Dalton D R Cannella A A | 2006 | Journal of Small Business Management2006，44，1： | 1 |
| 8 | Conditions influencing the precipitation of magnesium ammonium phosphate显示文摘 | Stratful I Scrimshaw M D Lester J N | 2001 | Water Res2001，35，17： | 1 |
| 9 | Erythropoietin promotes MCF-7 breast cancer cell migration by an ERK/mitogen-activated protein kinase-dependent pathway and is primarily responsible for the increase in migration observed in hypoxia显示文摘 | Lester R D Jo M Campana W M | 2005 | J Biol Chem2005，280，39： | 1 |
| 10 | Polymorphism in the 5'regulatory region of the B-lymphocyte activating factor gene isassociated with the Ro/La autoantibody response and serum BAFFlevels in primary Sjogren ’ s syndrome 显示文摘 | Nossent JC Lester S Zahra D | 2008 | Rheumatology(Oxford)2008，47，9： | 1 |
| 11 | The structure of Thalboume's brief Manic -Depressive scale显示文摘 | Rogers JR Lester D | 2010 | Psychol Rep2010，106，3： | 1 |
| 12 | Chemical additives in Bayer process显示文摘 | Lester A D | 1991 | Light Metals1991，，： | 1 |
| 13 | Peach (Prunus persica) Endopolygalacturonase cDNA isolation and mRNA analysis in melting and nonmelting peach cultivers显示文摘 | LESTER D R SPEIRS J ORR G | 1994 | Plant Physiology1994，105，： | 1 |
| 14 | Stewardship or agency? A social embeddedness reconciliation of conduct and performance in public family businesses显示文摘 | Le Breton-Miller I Miller D Lester R H | 2011 | Organization Science2011，22，3： | 1 |
| 15 | Romantic Attitudes towards Love in men and women显示文摘 | Lester D | 1985 | Psychological Rep6rts1985，56，： | 1 |
| 16 | Measuring Maslow's hierarchy of needs 显示文摘 | LESTER D | 2013 | Psychol Rep2013，113，1： | 1 |
| 17 | Suicidal ideation a- nd its correlates: testing the interpersonal theory of suicide in Chinese students 显示文摘 | ZHANG J LESTER D ZHAO S | 2013 | Arch Suicide Res2013，17，3： | 1 |
| 18 | Sugars in developing and mature fruits of several watermelon cμLtivars显示文摘 | Lester Paul L D | 1981 | J Amer Soe Hort Sci1981，106，3： | 1 |
| 19 | Determination of endocrine disrupters in sewage treatment and receiving waters显示文摘 | Rachel L Gomes Mark D Scrimshaw John N Lester | 2003 | Trends in Analytical Chemistry2003，22，10： | 1 |
| 20 | A multiplex RT-PCR Assay for the Rapid and Differential Diagnosis of Classical Swine Fever and Other Pestivirus infections显示文摘 | Heidy D Lester J Perez M | 2009 | Veterinary Microbiology2009，139，34： | 1 |
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