Impact of Platelets and Platelet-Derived Microparticles on Hypercoagulability Following Burn Injury

Abstract

An acute burn induced coagulopathy develops after scald injury, which evolves into a subacute, hypercoagulable state. Microparticles, specifically platelet-derived MPs (PMPs), have been suggested as possible contributors. We first developed a model of burn-induced coagulopathy and then sought to investigate the role of platelets and PMPs in coagulation after burn. We hypothesized that changes in circulating platelet and PMP populations after injury would contribute to the post-burn, hypercoagulable state. A murine scald model with 28% TBSA full thickness burn injury was utilized and blood samples were collected at intervals after injury. Circulating MP populations, platelet counts, overall coagulation, and platelet function were determined. Burn injury led to hypercoagulability on post-burn day one (PBD1), which persisted 6 days after injury (PBD6). On PBD1, there was a significant decrease in platelet numbers and a decline in platelet contribution to clot formation with a concomitant increase in circulating procoagulant PMPs. On PBD6, there was a significant increase in platelet numbers and in platelet activation with no change in PMPs compared with sham. Further, on PBD1 decreased ADP-induced platelet activation was observed with a contrasting increase in ADP-induced platelet activation on PBD6. We therefore concluded that there was a temporal change in the mechanisms leading to a hypercoagulable state after scald injury, that PMPs are responsible for changes seen on PBD1, and finally that ADP-induced platelet activation was key to the augmented clotting mechanisms 6 days after burn.

Circulating Microvesicles Are Elevated Acutely following Major Burns Injury and Associated with Clinical Severity

“…In the present study we did not evaluate platelet-derived MVs, because our primary focus was to investigate the roles of MVs in the acute inflammatory response, rather than coagulopathy. Hypercoagulability is an important component of severe burns pathophysiology, and indeed a recent animal study using mice has reported acute increases in circulating pro-coagulant platelet-derived MVs following a scalding injury [23]. However, coagulopathy may not be yet present at patient admission as part of the acute trauma response [24, 25] and therefore temporally distinct from acute onset SIRS.…”

Platelet-derived Extracellular Vesicles: An Emerging Therapeutic Approach

“…Recent studies showed that, in human serum, most EVs are P-EVs, although EVs can also be generated from white blood cells and cancer cells 15 - 17 . P-EVs have been found to participate in a variety of important biological and pathological processes via intracellular communication 18 , 19 , including clotting 20 , 21 , angiogenesis 22 , 23 , inflammation 24 , 25 , immunoregulation 3 , cellular prion protein transport 26 , and tumor progression 25 , 27 .…”

Platelet Priming Following Naturally Occurring Thermal Burn Injuries And Wildfire Smoke Exposure is Associated with Intracardiac Thrombosis in Feline Survivors

“…Observational studies in humans and murine models of burn injuries describe an initial hypercoagulable state despite the presence of thrombocytopenia [6][7][8][9] . This nding suggests that systemic platelet activation, which likely precedes platelet consumption, plays a crucial role in mediating hypercoagulability as a result of burn injuries 7,10,11 . Although the exact mechanisms of increased platelet activation in these patients are unknown, endothelial stress and injury during in ammation may facilitate platelet rolling and activation, and subsequent platelet-immune cell interactions via toll-like receptors (TLR) fueling further in ammation [12][13][14][15] .…”