Introduction
The natural course of partial-thickness burns is difficult to predict without robust markers to assist traditional evaluation. Here we assessed the potential of: activated protein C (APC), a protease with pleiotropic beneficial properties; its zymogen, protein C (PC); and their receptor, endothelial protein C receptor (EPCR), to predict outcomes for patients with burns.
Methods
We enrolled 88 patients with partial-thickness burns affecting 10-80% of the total body surface area in a single-centre prospective cohort study. Biopsies of normal and burned skin were collected from each patient as near as possible to admission date and immunostained for PC and EPCR. Plasma was collected on admission (day 0) and every three days for three weeks or until discharge, and analysed for PC, APC, soluble (s)EPCR levels, and inflammatory cytokines. Clinical data were recorded throughout admission.
Results
Epidermal EPCR levels were increased (p<0.05) while PC levels were reduced (p<0.01) in burn-damaged tissue when compared to normal tissue. Correspondingly, there was a marked reduction in day 0 plasma PC levels (p<0.0005), which recovered over time to a plateau by day 9. Day 0 plasma PC levels predicted increased support throughout admission, even when adjusted for depth, size and inhalational injury (p=0.013; odds ratio 0.879; model correctly predicts 89.7% of patients with 78.9% sensitivity and 92.3% specificity; ROC area-under-the-curve=0.961). APC reached a nadir on day 3 and then increased until day 15. Plasma levels of sEPCR and cytokines did not vary significantly over the study period.
Conclusion
PC expression is decreased in burn-damaged tissue. Day 0 plasma PC level is a better predictor of increased support throughout admission than burn just depth, burn size and inhalational injury together. Although further studies are required, plasma PC levels may be a novel marker for predicting outcomes in patients with severe burns.