While our study identifies correlations of pH with the effectiveness of rFVIIa, Maraviroc a recently conducted study by Meng et al., suggests that a decrease in temperature from 37°C to 33°C also results in a reduction of rFVIIa’s activity by 20% [17]. The Australia and New Zealand Haemostasis Registry also presented graphical

data pertaining to the effect of decreases in temperature and response of bleeding to rFVIIa administration in trauma patients. In fact, for ≤ 33.5°C, 70.7% of trauma patients had an unchanged bleeding response; and for normal physiologic temperature range (36.6-37.5°C), 38% had an unchanged bleeding response after receiving rFVIIa [25]. The registry also found that as pH is decreased, the activity of rFVIIa is reduced [25]. Finally, a study by Knudson et al analyzed subgroup of patients who received rFVIIa and lived at least 24 hr versus those who received rFVIIa and died. In

this study, predictors of death included a low pH, a low platelet count, a more severe base deficit, and a higher transfusion rate [27]. In our present study, higher transfusion rates were also associated with failure of rFVIIa and increased mortality. These findings indicate that the efficacy of rFVIIa in coagulopathic, acidotic patients with high rates of bleeding Staurosporine manufacturer is compromised with pH and temperature reductions. As the patient’s condition deteriorates over time due to failure of standard therapies, the pH drastically decreases and the activity of rFVIIa is virtually nonexistent, which makes it a challenge to consider the use of rFVIIa as a last resort. Thus, current recommendations on its use as an alternative to manage coagulopathy before in

trauma when other interventions fail should be taken with caution. The high monetary cost of rFVIIa administration, with no strong evidence of survival benefit [7, 11] and increased risks of thrombotic complications [12], also calls for a review of guidelines recommending the use of this medication for traumatic coagulopathy. The cost-effectiveness of using rFVIIa as a last resort therapy for critical bleeding requiring massive transfusion was recently evaluated [19]. The incremental costs of rFVIIa increased with severity of illness and transfusion requirement, and were unacceptably high (> US$100,000 per life-year) for most patients [19]. Overall, thought must be given to the expense of rFVIIa, and its utility as a last resort. Alternatively, a more affordable and effective management strategy for traumatic coagulopathy is available. A recently conducted large randomized control trial (CRASH-2) involving 20,000 patients found that tranexamic acid reduced the risk of death in hemorrhaging trauma patients and should be recommended in bleeding trauma situations [28].