Non-severe burn injury causes sustained hyperreactivity in human and mouse platelets.

Blair Johnson^1,2, Andrew Stevenson^1,2, Mark Fear^1,2, Fiona Wood^1,2,3, Matthew Linden²,
¹Burn Injury Research Unit, UWA, Nedlands, WA, Australia
²School of Biomedical Science, UWA, Nedlands, WA, Australia
³Burns Service WA, Department of Health, Murdoch, WA, Australia

Abstract

Epidemiological studies have established that burn survivors have heightened cardiovascular disease risk compared to controls. Individuals who present to a hospital for treatment of a burn wound (independently of total body surface area (TBSA) involvement) are more frequently hospitalised for ischemic heart disease, decades after injury. Blood platelets are key cellular mediators of cardiovascular disease, contributing both to accelerated atherogenesis, plaque instability and end-stage thrombotic complications of atherosclerosis. To investigate platelet involvement in post-burn cardiovascular risk, platelet reactivity was assessed in patients at 2- and 6-weeks after non-severe (TBSA < 20%) burn injury, compared to age/sex-matched controls, and a murine model of 8% TBSA full-thickness burn injury. Platelets were incubated with canonical agonists both in whole blood or following isolation and exchange with control plasma. Activation based on expression of the GPIIb/IIIa PAC1-binding site, CD62P (P-selectin), or formation of monocyte-platelet aggregates was measured by flow cytometry. In vivo thrombosis in response to a modified Folt’s model of vascular injury was assessed. Burn survivors were found to have elevated frequencies of circulating monocyte-platelet aggregates, and platelets were hyperreactive to canonical agonists, primarily collagen. Murine platelets also demonstrated sensitivity to ex vivo collagen-mediated activation, however this did not impact in vivo measurements of thrombosis. This study demonstrates the persistence of a small but significant increase in platelet hyperreactivity following burn injury, independent of plasma-mediated augmentation. Although our data does not suggest this heightened platelet sensitivity modulates thrombosis following vascular injury, the contribution of sub-clinical platelet hyperreactivity to accelerating atherogenesis merits further exploration.

Biography

Blair Johnson (soon to be Dr. Johnson at the time of presentation) has continued to pursue evidence of post-burn immune and platelet dysfunction following the submission of his PhD thesis earlier this year. His thesis considered the short and long-term changes to immune profile in burn patients, as well as prolonged increases in platelet responsiveness – foundational work towards understanding systemic impacts of the most common burn injuries (as opposed to, and expanding on, research in severe burns). Blair continues to broaden the scope of this enquiry by investigating persistent metabolic impacts of burn injuries, and supporting new research students.