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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 | Expression of cell adhesion molecules in corneal graft failure显示文摘 | Whitcup SM Nussenblatt RB Price FW Jr | 1993 | Cornea1993，12，6： | 1 |
| 3 | Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase显示文摘 | Parad RB Michele T Allred E Price A Rosenfeld W | 2003 | Pediatrics2003，111，3： | 1 |
| 4 | Modeling interindividual variation in physiological factors used in PBPK models of humans 显示文摘 | Price PS Conolly RB Chaisson CF Gross EA Young JS Mathis ET | 2003 | Crit Rev Toxicol2003，33，5： | 1 |
| 5 | Protein-calorie malnutrition in a community hospital显示文摘 | Willard MD Gilsdorf RB Price RA | 1980 | JAMA1980，243，： | 1 |
| 6 | Astigmatism reduction clinical trail:a multicenter prospective evaluation of the predictability of arcuate keratotomy;evaluation of surgical nomogram predictability;the ARC-T Study Group显示文摘 | Price FW Grene RB Marks RG | 1995 | Arch Ophthalmol1995，113，： | 1 |
| 7 | Light energy transmission through cured resin composite and human dentin显示文摘 | Price RB Murphy DG Derand T | 2000 | Ouintessence Int2000，31，9： | 1 |
| 8 | The effect of distance from light source on light intensity from curing lights显示文摘 | Felix CA Price RB | 2003 | J Adhes Dent2003，5，4： | 1 |
| 9 | Effects of Intravenous Ketamine on Explicit and Implicit Measures of Suicidality in Treatment-Resistant Depression显示文摘 | Price RB Nock MK Charney DS | 2009 | Biol Psychiatry2009，66，5： | 1 |
| 10 | A review of preweighed,packaged die stone versus bulk die stone use in a dental school显示文摘 | Price RB Doyle MG Bannerman RA | 1998 | J Prosthodont1998，7，1： | 1 |
| 11 | Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression显示文摘 | Price RB Nock MK Charney DS | 2009 | Biol Psychiatry2009，66，5： | 1 |
| 12 | Protein-calorie malnu- trition in a community hospital显示文摘 | Willard MD Gilsford RB Price RA | 1980 | JAMA1980，243，17： | 1 |
| 13 | The effect Of distance from light source on light intensity from curing lights 显示文摘 | Felix CA Price RB | 2003 | J Adhes Dent2003，5，4： | 1 |
| 14 | Amino acid neurotransmitters assessed by proton magnetic resonance spectroscopy: relationship to treatment resistance in major depressive disorder 显示文摘 | Price RB Shungu DC Mao X | 2009 | Biol Psychiatry2009，65，： | 1 |
| 15 | Deficient prefrontal attentional control in late-life generalized anxiety disorder: an fMRI investigation显示文摘 | Price RB Eldreth DA Mohlman J | 2011 | Transl Psychiatry2011，1，： | 1 |
| 16 | Intra-and inter-brand ac- curacy of four dental radiometers 显示文摘 | Price RB Labile D Kazmi S | 2012 | Clin Oral Investig2012，16，3： | 1 |
| 17 | Protein-calorie malnutrition in a community hospital 显示文摘 | Gilsdorf RB Price RA | 1980 | JAMA1980，243，： | 1 |
| 18 | Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment- resistant depression 显示文摘 | Price RB Nock MK Chatney DS | 2009 | Biol Psychiat2009，66，5： | 1 |
| 19 | Modeling interindividual variation in physiological factors used in PBPK models of humans显示文摘 | Price PS Conolly RB Chaisson CF | 2003 | Crit Rev Toxicol2003，33，5： | 1 |
| 20 | Knoop hardness of ten resin composites irradiated with high-power LED and quartztungsten- halogen lights显示文摘 | Price RB Felix CA Andreou P | 2005 | Biomaterials2005，26，15： | 1 |
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