The effect of temperature and pH on the activity of factor VIIa: Implications for the efficacy of high-dose factor VIIa in hypothermic and acidotic patients

Background: Recombinant coagulation factor VIIa (FVIIa) is, approved for treating hemophiliacs with inhibitors. High-dose FVIIa has also been used off-label to manage hemorrhage in trauma and surgical patients, many of whom also develop hypothermia and acidosis. Methods: We examined the activity of FVIIa on phospholipid vesicles in the presence and absence of tissue factor (TF) and on platelets as a function of temperature and pH. Results: FVIIa activity on phospholipids and platelets was not reduced at 33degreesC compared with 37degreesC. The activity of FVIIa/TF was reduced by 20% at 33degreesC compared with 37degreesC. A pH decrease from 7.4 to 7.0 reduced the activity of FVIIa by over 90% and FVIIa/TF by over 60%. Conclusion:. FVIIa should be effective in enhancing hemostasis in hypothermic patients. However, because the activity of FVIIa is so dramatically affected by pH, its efficacy may be reduced in acidotic patients.