ABSTRACT
Burn-induced tissue loss is partly related to secondary expansion of necrosis into vital dermis neighbouring the initial burn injury. An important factor herein is the severe loss of perfusion of the burn wound, probably caused by microvascular damage induced by the intense local inflammatory responses as well as burn-induced hypercoagulation. We hypothesize that the formation of Neutrophilic Extracellular Traps (NETs) play an important role in this. The purpose of this study was to investigate post-burn intravascular thrombosis, NETs formation and the coagulant state in the microvasculature of burns in both animal models and patients.
We used two in vivo burn wound models: rats and pigs. In rats the entire wound was excised at day 14 post-burn and in pigs burn wound biopsies were collected at different time points up to 60 days post-burn. To confirm the data in patients, eschar from the burn wound was obtained from burn wound patients at different time points after wounding. The number of intravascular thrombi, the presence of intravascular NETs and the number of TF positive blood vessels in the burn wound was determined.
In rats, a significant increase in intravascular thrombi and TF expression was observed 14 days post-burn, that in majority coincided with NETs. In pigs, a significant increase in intravascular thrombi and TF expression was found over time up to 60 days post-burn, that in majority coincided with NETs too. Also in eschar of burn wound patients, a significant increase in intravascular thrombi was noted, that in majority coincided with NETs, already 0.5 days post-burn and remained elevated up to 46 days post-burn.
This study shows the presence of NETosis in microcirculatory thrombosis of burn wounds and a switch in the microcirculatory endothelium towards a pro-coagulant phenotype. This article is protected by copyright. All rights reserved.
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