Nicolas J Prat1, Maryanne C Herzig, Stefan Kreyer, Robbie K Montgomery, Bijaya K Parida, Katharina Linden, Vittorio Scaravilli, Slava M Belenkiy, Leopoldo C Cancio, Andriy I Batchinsky, Andrew P Cap. 1. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Brendan D Cowled; Melanie Bannister-Tyrrell; Mark Doyle; Henry Clutterbuck; Jeff Cave; Alison Hillman; Karren Plain; Caitlin Pfeiffer; Michael Laurence; Michael P Ward Journal: Front Vet Sci Date: 2022-02-15
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Authors: B D Cowled; A Hillman; M P Ward; H Clutterbuck; M Doyle; J Webb Ware; M Thomas; K Plain; R Barwell; M Laurence; C Pfeiffer Journal: Aust Vet J Date: 2022-05-05 Impact factor: 1.343
Authors: Ashley N Sharpe; Catherine T Gunther-Harrington; Steven E Epstein; Ronald H L Li; Joshua A Stern Journal: Sci Rep Date: 2020-02-14 Impact factor: 4.379