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Heparin resistance in severe thermal injury:a prospective cohort study

Burns & Trauma 2021年第1期9卷 157-169页

作者： 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 Scar Free Foundation Birmingham Centre for Burns Research University Hospitals Birmingham Foundation TrustQueen Elizabeth Hospital BirminghamMindelsohn WayBirminghamB152WBUK Department of Haematology University Hospitals Birmingham Foundation TrustMindelsohnWayBirminghamB152WBUK Institute of Inflammation and Ageing University of BirminghamBirminghamB152TTUK NIHR Surgical Reconstruction and Microbiology Research Centre University Hospitals Birmingham Foundation TrustMindelsohn WayBirminghamB152WBUK

Background:Low molecular-weight heparin(LMWH)is routinely administered to burn patients for *** studies have reported heparin resistance,yet the mechanism(s)and prevalence have not been systematically *** 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 ***:Blood was sampled from>15%total body surface area(TBSA)burn patients receiving LMWH on days 5,10 and *** anti-factor Xa(AFXa)activity,anti-thrombin(ATIII)activity,cellfree DNA(cfDNA)levels and nucleosome levels were *** effects regression was adjusted for multiple confounders,including injury severity and ATIII activity,and was used to test the association between nucleosomes and ***:A total of 30 patients with severe burns were *** 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 *** levels were negatively correlated with AFXa(r=−0.29,p=0.050)consistent with 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 ***:Heparin resistance is a prevalent issue in severe *** levels were increased post-burn,and showed an inverse association with AFXa consistent with the hypothesis that they ma

关键词： Burn Heparin resistance Low molecular-weight heparin Nucleosomes Neutrophil extracellular traps Factor-Xa Thrombosis Enoxaparin NETosis

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