Editors' ChoiceWound Healing

Burn injuries cast their nets in blood vessels

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Science Translational Medicine  02 Aug 2017:
Vol. 9, Issue 401, eaao0979
DOI: 10.1126/scitranslmed.aao0979

Abstract

Neutrophil extraceullar traps (NETs) cause secondary expansion of tissue necrosis in local and remote tissues due to microvascular hypercoagulation.

After the recent 4 July holiday, burn surgeons are finally recovering from the influx of firework-related burn injuries. Although nearly a month has passed, the skin microvasculature in the region of the burn and in remote regions remains hypercoagulable (increased risk of clotting). Areas of deeper burns are known to lack vascular perfusion, but the cause of burn progression or coagulation of tissue that initially does not appear necrotic remains unknown. A recent study by Korkmaz and colleagues demonstrates that neutrophil extraceullar traps (NETs) are present in coagulated vessels at the burn wound site and in adjacent tissues up to 60 days after burn. It is known that NETs stimulate thrombosis; however, the role of NETs in burn wounds changing from a partial to a full thickness injury has not been previously described.

Korkmaz et al. first analyzed intravascular thrombi in a rat burn model and found an increased number of intravascular thrombi not only in burned tissue but also in remote unburned skin. They then demonstrated that these thrombi colocalized with NETs. Next, using a pig burn wound model, they found an increase in microvascular thrombi up to 60 days after burn injury and a colocalization of thrombi and NETs. Last, they analyzed skin samples from a cohort of burn patients and found increased average number of thrombi/mm2 compared with healthy control skin. The lack of organization of these thrombi indicated that they were formed recently, demonstrating sustained hypercoagulability.

This study expands the known role of NETs in hypercoagulation and dysregulated wound healing into burn wounds. Interestingly, NET dissolving therapies [dornase alfa or doxyribonuclease (DNase)] have been used anecdotally to treat hypercoagulation seen after inhalation injury. Given the significant drug development in NET targeted therapies, including DNase and peptidyl arginine deiminase type IV (PAD4) inhibitors, these findings will allow for their translation into burn care. Thus, systemic and topical treatments for burn care targeting NET-induced hypercoagulation could revolutionize burn care and decrease the deleterious NETs cast by firework-related injuries in time for 4 July 2018.

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