Prat Nicolas J, Herzig Maryanne C, Kreyer Stefan, Montgomery Robbie K, Parida Bijaya K, Linden Katharina, Scaravilli Vittorio, Belenkiy Slava M, Cancio Leopoldo C, Batchinsky Andriy I, Cap Andrew P
From the US Army Institute of Surgical Research, (N.J.P., M.C.H., S.K., R.K.M., B.K.P., K.L., V.S., S.M.B., L.C.C., A.I.B., A.P.C.), JBSA Fort Sam Houston, Texas; Armed Forces Biomedical Research Institute, (N.J.P.) France; University Hospital Bonn (S.K., K.L.), Bonn, Germany; Department of Anesthesia, Critical Care and Emergency (V.S.), Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Department of Anesthesiology (S.M.B.), West Virginia University School of Medicine, Morgantown, West Virginia; and The Geneva Foundation, (A.I.B.) Tacoma, Washington.
J Trauma Acute Care Surg. 2017 Jul;83(1 Suppl 1):S59-S65. doi: 10.1097/TA.0000000000001472.
Smoke inhalation and burn injury remain a major source of morbidity and mortality. There is known dysregulation of hemostasis in burn patients, but either hypercoagulation or hypocoagulation states are reported. Sheep are an established animal model for studying burn pathology and provide robust data on hemostatic function at baseline and after injury.
After an IACUC-approved protocol, 15 sheep were anesthetized and subjected to a 40% full thickness burn with smoke inhalation. Blood was sampled at baseline, 1 day postinjury (early effects) and days 2, 3, and 4 (late effects) after injury. Assays at each timepoint assessed: hemostatic function by thromboelastography (TEG), platelet counts and function by flow cytometry and aggregometry, coagulation protein levels, and free hemoglobin. Data were analyzed by the Wilcoxon paired test (nonparametric) with significance set at less than 0.05.
By 24 hours postinjury, platelet counts had dropped, whereas the percent activated platelets increased. Absolute platelet functional response to the agonist adenosine diphosphate (ADP) decreased, whereas response to collagen showed no significant difference. On a per platelet basis, ADP response was unchanged, whereas the collagen response was elevated. Prothrombin time and activated partial thromboplastin time were prolonged. TEG parameters decreased significantly from baseline. Fibrinogen and factor V were trending up; coagulation proteins ATIII, factors IX and X were decreased.Late effects were followed in six animals. At day 4, platelet counts remained depressed compared with baseline with a nadir at day 2; responses to agonist on a per platelet basis remained the same for ADP and stayed elevated for collagen. Platelets continued to have elevated activation levels. Fibrinogen and factor V remained significantly elevated, whereas TEG parameters and prothrombin time, factors IX and X returned to near baseline levels.
Coagulation parameters and hemostasis are dysregulated in sheep after smoke inhalation and burn. By 24 hours, sheep were hypocoagulable and subsequently became hypercoagulable by day 4. These results suggest a three-stage coagulopathy in burn injuries with a known early consumptive hypercoagulable state which is followed by a relatively hypocoagulable state with increased bleeding risk and then a return to a relatively unknown hypercoagulability with increased susceptibility to thrombotic disorders.
烟雾吸入和烧伤仍是发病和死亡的主要原因。已知烧伤患者存在止血功能失调，但有报道称其处于高凝或低凝状态。绵羊是研究烧伤病理的成熟动物模型，可提供基线及受伤后止血功能的可靠数据。
经机构动物护理与使用委员会（IACUC）批准方案后，对15只绵羊进行麻醉，造成40%体表面积的全层烧伤并伴有烟雾吸入。在基线、受伤后1天（早期效应）以及受伤后第2、3和4天（晚期效应）采集血液样本。每个时间点的检测项目包括：通过血栓弹力图（TEG）评估止血功能，通过流式细胞术和凝集测定法评估血小板计数及功能，检测凝血蛋白水平以及游离血红蛋白。数据采用Wilcoxon配对检验（非参数检验）进行分析，显著性设定为小于0.05。
受伤后24小时，血小板计数下降，而活化血小板百分比增加。血小板对激动剂二磷酸腺苷（ADP）的绝对功能反应降低，而对胶原的反应无显著差异。以单个血小板计，ADP反应未变，而胶原反应升高。凝血酶原时间和活化部分凝血活酶时间延长。TEG参数较基线显著降低。纤维蛋白原和因子V呈上升趋势；凝血蛋白抗凝血酶III（ATIII）、因子IX和X降低。对6只动物进行了晚期效应观察。在第4天，血小板计数与基线相比仍较低，在第2天达到最低点；单个血小板对激动剂的反应中，ADP反应保持不变，胶原反应仍升高。血小板活化水平持续升高。纤维蛋白原和因子V仍显著升高，而TEG参数、凝血酶原时间、因子IX和X恢复至接近基线水平。
烟雾吸入和烧伤后绵羊的凝血参数及止血功能失调。受伤后24小时，绵羊处于低凝状态，随后在第4天变为高凝状态。这些结果提示烧伤损伤存在三阶段凝血病，已知早期为消耗性高凝状态，随后是出血风险增加的相对低凝状态，然后是对血栓形成性疾病易感性增加的相对未知的高凝状态。
