However, in the BI 10773 in vivo context of massive hemorrhage, there are potential limiting factors such as acidosis and refractory shock. From this study, a pH of 7.02 had the best sensitivity on the ROC curve for discriminating survivors and non-survivors. A pH > 7.02 was 100% sensitive at identifying potential survivors, reassuring the clinician that no probable survivors could have been AZD3965 order missed if this pH cut-off was adopted. Thus, a pH of 7.02 may be used as a potential guideline or measure at which the administration of rFVIIa should not be considered for patients who are severely acidotic. The pH level of these

patients appeared to be a key determining factor in the success of rFVIIa. As noted, there was a remarkable 100% mortality noted in coagulopathic and severely

acidotic patients (pH ≤ 7.02) who had high bleeding rates, despite the use of rFVIIa. This is corroborated by recent research suggesting that the efficacy of rFVIIa decreases by 90% when the body pH decreases from 7.4 to 7.0 [17]. However, in a recent animal model of lactic acidosis, the effectiveness of rFVIIa in correcting abnormal INR values at a mean pH of 7.14 was unaffected [18]. This suggests that other factors may influence its efficacy in clinical settings. In keeping with our findings, data from the Australia and GSK2126458 supplier New Zealand Haemostasis Registry on 10 years of the use of rFVIIa in Australia and New Zealand which reports on the outcomes of 2181 trauma cases, the single most important predictor of the effect of rFVIIa

Phosphoprotein phosphatase on bleeding and 28-day mortality was pH [25]. In their multivariate analysis, for every 0.1 decline in pH, there were associated increases in non-responders to rFVIIa use and mortality rates [25]. Their unadjusted analysis on the relationship between 28-day mortality and pH showed that patients with pH < 6.90 had a mortality rate of 98% while the group with 7.3025]. Although the pH of 6.90 did not coincide with our threshold of 7.02, the pattern is apparent that mortality percentage drastically increases with decreases in pH. Logistic regression analysis was conducted and values for the odds ratio were obtained for the effect on bleeding and pH, as well as 28-day mortality and pH. For both, an inverse correlation was seen, in that when pH decreased, the odds ratio for mortality increased [25]. Furthermore, outside of the trauma literature, a study by Karkouti et al. found that the administration of rFVIIa should be expedited in order to increase its efficacy in cardiac surgery [24]. An additional factor that must be considered is the impact of other variables, such as rate of bleeding and baseline physiologic factors on rFVIIa, particularly temperature.