In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures

Abstract

Recombinant activated factor VII (rFVIIa) is currently administered off-label to control diffuse coagulopathic bleeding of patients with traumatic injuries. These patients are often cold, acidotic, and coagulopathic upon arrival and each responds differently to rFVIIa therapy. This study investigated the effects of hypothermia on clotting and the potential benefit of rFVIIa administration on blood coagulation at different hypothermic temperatures. Citrated blood samples were collected from eight healthy volunteers (20-45 years old) and incubated at 37 degrees C, 34 degrees C, 31 degrees C, and 28 degrees C for 30 minutes. rFVIIa (1.26 microg/mL equivalent to 90 microg/kg in vivo dose) or vehicle solution (saline) was added to each blood sample, incubated (10 minutes), and analyzed at the respective temperatures by standard coagulation tests and thrombelastography. The clot reaction time of blood samples, measured as prothrombin time, activated partial thromboplastin time, and R time (thrombelastography analysis), was significantly prolonged at 31 degrees C or below compared with at 37 degrees C. The clot formation rate ([alpha] angle, maximum clotting velocity [Vmax]) was decreased at all cold temperatures. Maximum clot strength (maximum amplitude) was only affected (reduced) at 28 degrees C. Addition of rFVIIa shortened the prothrombin time, activated partial thromboplastin time, and R times at every temperature, surpassing the normal (37 degrees C) temperature values in 31 degrees C and 34 degrees C cold samples. Similarly, clot formation rate parameters (clotting time, [alpha] angle, Vmax) were also improved by rFVIIa addition and normothermic values were restored in 31 degrees C and 34 degrees C cold blood samples. rFVIIa did not affect maximum amplitude at any temperature. Mild to moderate hypothermia delayed the initial clot reaction and reduced clot formation rate without affecting ultimate clot strength. FVIIa effectively compensated for the adverse effects of hypothermia except in severe cases. These results suggest that administration of FVIIa should be beneficial in enhancing hemostasis in hypothermic trauma patients without the need for prior correction of the patient's body temperature.