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

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Abstract
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. 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. FVIIa activity on phospholipids and platelets was not reduced at 33 degrees C compared with 37 degrees C. The activity of FVIIa/TF was reduced by 20% at 33 degrees C compared with 37 degrees C. A pH decrease from 7.4 to 7.0 reduced the activity of FVIIa by over 90% and FVIIa/TF by over 60%. 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.