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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 | GTM: The generative topographic mapping显示文摘 | Bishop C M Svensen M Williams C K I | 1998 | Neural Computation1998，10，1： | 1 |
| 5 | Chromosomal distribution of en- dogenous Jaagsiekte sheep retrovirus proviral sequences in the sheep genome 显示文摘 | Carlson J Lyon M Bishop J | 2003 | J Virol2003，77，17： | 1 |
| 6 | APOBEC-mediated viral restriction: not simply editing? 显示文摘 | Holmes R K Malim M H Bishop K N | 2007 | Trends Biochem Sci2007，32，3： | 1 |
| 7 | Molecular themes in oncogenesis显示文摘 | BISHOP J M | 1991 | Cell1991，64，2： | 1 |
| 8 | Probabilistic principal component analysis显示文摘 | TIPPING M BISHOP C | 1999 | Journal of the Royal Statistical Society Series B1999，21，3： | 1 |
| 9 | Cloning and characterization of a growth factor-inducible eyclooxygenase gene from rat intestinal epithelial cells 显示文摘 | DuBois RN Tsujii M Bishop P | 1994 | Am J Physiol1994，266，51： | 1 |
| 10 | Contingent Valuation of En- vironmental Assets: Comparison with a Stimulated Market 显示文摘 | Bishop R C Heberlein T A Kealy M J | 1983 | Nat- ural Resources Journal1983，23，： | 1 |
| 11 | Assessment of compromised fracture healing显示文摘 | Bishop JA Palanca AA Bellino M J | 2012 | J Am Acad Orthop Surg2012，20，5： | 1 |
| 12 | Multivariate analysis of mainstream tobacco smoke particulate phase by headspace solid-phase micro extraction coupled with comprehensive two-dimensional gas chromatography-time-offlight mass spectrometry显示文摘 | BROKL M BISHOP L WRIGHT C G | 2014 | Journal of Chromatography A2014，1370，： | 1 |
| 13 | Parabens as urinary biomarkers of exposure in humans显示文摘 | Ye X Y Bishop A M Needham L L | 2006 | Environmental Health Perspectives2006，114，： | 1 |
| 14 | 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 |
| 15 | The biomimetic iron-mediated degradation of arteflene (Ro-42-1611), an endoperoxide antimalarial implications for the mechanism of antimalarial activity 显示文摘 | O'Neill P M Bishop L P Sesrle N L | 1997 | Tet rahedron Lett1997，38，24： | 1 |
| 16 | Concurrent analy- sis of nose and groin swab specimens by the IDI-MRSA PCR assay is comparable to analysis by individual-specimen PCR and routine culture assays for detection of colonization by methicillin-resistant Staphylococcus aureus 显示文摘 | BISHOP E J GRABSCH S A BALLARD B M | 2006 | J Clin Microbio12006，44，8： | 1 |
| 17 | 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 |
| 18 | Early clinical experience with a new videolaryngoscope (GlideScope) in 728 patients显示文摘 | Cooper R M Pacey J A Bishop M J McCluskey S A | 2005 | Can J Anaesth2005，52，： | 1 |
| 19 | Heparan sulphate proteoglycans fine- tune mammalian physiology显示文摘 | Bishop J R Schuksz M Esko J D | 2007 | Natute2007，446，7139： | 1 |
| 20 | The Medical Emergency leam显示文摘 | L~e A Bishop ( llilhnan K M el al | 1995 | Anaeslhesia and intensive care1995，23，2： | 1 |
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