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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 | Problems in the management of typeⅢ (severe) open fractures:a new classification of type Ⅲ open fracture显示文摘 | Gustiol RB Mendoza RM Williams DN | 1984 | J Trauma1984，24，： | 2 |
| 3 | Problems in the man agement of type Ⅲ (severe) open fractures: a new classification of type Ⅲ open fractures显示文摘 | Gustilo RB Mendoza RM Williams DN | 1984 | J Trauma1984，24，： | 1 |
| 4 | Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarrays and RNA interference显示文摘 | Williams N S Gaynor RB Scoggin S | 2003 | Clin Cancer Res2003，9，： | 1 |
| 5 | Incidence of opportunistic and other in-fections in HIV-infected children in the HAART era显示文摘 | Gona P Van Dyke RB Williams PL Dankner WM Chemcff MC Nachman SA | 2006 | JAMA2006，296，3： | 1 |
| 6 | The activation of matriptase requires its noncatalytic domains,serine protease domain,and its cognate inhibitor显示文摘 | Oberst MD Williams CA Dickson RB | 2003 | J Biol Chem2003，278，26： | 1 |
| 7 | Problemin the manage ment of type Ⅲ (sever)open fracture: a new classification of type Ⅲ open fracture显示文摘 | Gustilo RB Mendoza RM Williams DN | 1984 | J Trauma1984，24，8： | 1 |
| 8 | Upregulation of the esophago-UES relaxation response:a possible pathophysiological mechanism in suspected reflux laryngitis显示文摘 | Szczesniak MM Williams RB Brake HM | 2010 | Neurogastroenterol Motil2010，22，4： | 1 |
| 9 | Problems in the management of type Ⅲ(severe) open fracture A new classification of type Ⅲopen fractures显示文摘 | Gustilo RB Mendoza RM Williams DN | 1984 | J Trauma1984，24，8： | 1 |
| 10 | Myocyte-enriched calcineurin-interacting protein,MCIPI,inhibits cardiac hypertrophy in vivo显示文摘 | Rothermel BA McKinsey TA Vega RB Nieol RL Mammen P Yang J Antos CL Shelton JM Bassel-Duby R Olson EN Williams RS | 2001 | Proo Nail Aead Sei U S A2001，98，6： | 1 |
| 11 | Intercellular adhesion molecule-1 deficient mice are protected against ischemic renal injury 显示文摘 | Kelly KJ Williams WW Jr Coluin RB | 1996 | J Clin Invest1996，97，4： | 1 |
| 12 | Problems in the management of type Ⅲ (severe) open fractures : a new classification of type Ⅲ open fractures 显示文摘 | Gustilo RB Mendoza RM Williams DN | 1984 | J Trauma1984，8，： | 1 |
| 13 | Problems in the management of type Ⅲ (severe)open fractures:a new classification of type Ⅲ open fractures 显示文摘 | GUSTILO RB MENDOZA RM WILLIAMS DN | 1984 | Trauma1984，24，8： | 1 |
| 14 | Clinical evaluation of injuries to the aeromioclavieular and sternoclavicular joints 显示文摘 | Garretson RB 3^rd Williams GR Jr | 2003 | Clin Sports Med2003，22，： | 1 |
| 15 | Development,physicochemical characterization and preclinica efficacy evaluation of a water soluble glucan sulfate derived from Saccharomyces cerevisiae显示文摘 | Williams DL Pretus HA Mcnamee RB | 1991 | Immunopharmacology1991，22，3： | 1 |
| 16 | Biomechanics, diagno- sis, and treatment outcome in inflammatory myopathy presenting as oropharyngeal dysphagia 显示文摘 | Williams RB Grehan M J Hersch M | 2003 | Gut2003，52，4： | 1 |
| 17 | Problems in the treatment of type Ⅲ (severe) open fracture显示文摘 | Gustilo RB Mednoza RM Williams DN | 1984 | J Trauma1984，24，： | 1 |
| 18 | A compartmentalised model for the estimation of the cost of coccidiosis to the world's chicken production industry显示文摘 | WILLIAMS RB | 1999 | International Journal for Parasitology1999，29，8： | 1 |
| 19 | Problems in the manage- ment of type Ⅲ(severe)open fractures: a new classification of type lII open fracture 显示文摘 | Gustilo RB Mendoza RM Williams DN | 1984 | J Trauma1984，24，8： | 1 |
| 20 | Identification and validation of genes involved in the pathogenesis of colorectal cancer using cDNA microarray and RNA interference显示文摘 | Williams NS Gaynor RB Scoggin S | 2003 | Clin Cancer Res2003，9，3： | 1 |
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