Background:Cytochrome c is an intermembrane mitochondrial protein that is released to the bloodstream following mitochondrial injury.Methods and results:We developed an electrochemiluminescence immunoassay to measure cytochrome c in human and rat plasma, which showed high sensitivity with broad dynamic range (2-1200 ng/mL in humans and 5-500 ng/mL in rat) and high assay reproducibility (inter-assay coefficient <6% in humans and <10% in rat). In patients after blunt trauma, plasma cytochrome c directly correlated with injury severity. In rats after cardiac resuscitation, plasma cytochrome c inversely correlated with survival and responsiveness to mitochondrial protective interventions.Conclusions:The cytochrome c assays herein presented have high sensitivity, wide dynamic range, and high reproducibility well suited for biomarker of mitochondrial injury.

METHODS:The registry of an urban level 1 trauma center was queried for adult patients who received at least 6 units of packed red blood cells within 4 hours of presentation. Bivariate analysis, multiple logistic regression, and propensity score matching were performed.RESULTS: 441 patients were included. Cryoprecipitate was more commonly administered to patients with lower revised trauma scores (6.8174 vs 7.5500, p¼0.008), decreased Glasgow coma scale (12 vs 15, p¼0.004), and increased lactate (7.53 vs 4.90, p<0.0001). Early (4 hour) mortality was greater among patients who did not receive cryoprecipitate in univariate analysis (15.6% vs 6.1%, p¼ 0.013). Neither multiple logistic regression nor propensity score matching revealed that cryoprecipitate administration was associated with a difference in inpatient mortality (OR 0.809, p¼0.543; average treatment effect on the treated 0.07%, p¼0.496).CONCLUSION: Patients receiving cryoprecipitate were more severely injured at presentation and had increased mortality at four hours. Both multivariable logistic regression and propensity score analysis failed to show that early administration of cryoprecipitate impacts mortality for exsanguinating trauma patients. The prospect of definitively assessing the utility of cryoprecipitate in exsanguinating hemorrhage warrants prospective investigation.

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