Efficacy of Low-Dose Recombinant Activated Factor VII (rFVIIa) in Massively Transfused Trauma Patients with Coagulopathy.
Authors: Quillen Karen , Hirsch Erwin , Bauza Graciela 
Published: April 2020

Abstract
Introduction: Coagulopathy in the setting of massive transfusion is multifactorial: the dilutional effect of blood loss and inadequate replacement of coagulation factors and platelets, DIC from hypotension and tissue injury, consumption of coagulation factors and platelets at multiple sites of endothelial damage, hypothermia, and impaired hepatic synthesis of coagulation factors in severe hepatic injury are all contributing factors. rFVIIa in "standard" or higher doses (90 μg/kg is the approved dose for hemophilia patients with inhibitors) has been reported to reverse coagulopathy in trauma-related massive transfusion. We postulate that lower doses of rFVIIa may be efficacious.
Case series: 8 patients (M:F 1:1, age range 17–78, mean 52 yrs) with blunt trauma and multiorgan injury excluding head injury (Injury Severity Score 18–43, mean 30) had received massive transfusion within the first 24 hr of admission and had persistent bleeding despite resuscitative surgery. The first 3 patients had severe hepatic injury. Blood component support (mean number of units) included: 24 units of packed red cells (range 10–46), 12 units of FFP (range 5–32), 19 units of platelets (range 5–35), and 14 units of cryoprecipitate (range 0–20). Mean INR was 1.42 (range 1.24–1.90). Hematology consultation was obtained, and patients received 1.2 or 2.4 mg rFVIIa with the goal of achieving a dose of 20 μg/kg. Weight-based dosing was calculated post-hoc and the mean dose for the series was 21 μg/kg (range 11–37 μg/kg). Mean post-rFVIIa INR was 0.95 (range 0.84–1.08; vs 1.42, p=0.0002); INR correction apparently persisted for 10–12 hr in 7 out of 8 patients. There was good correlation between INR correction and bleeding cessation. Mean blood component usage (in 7 patients) in the 24-hr period post-rFVIIa included: 5 units of packed red cells (range 2–10; vs 24, p=0.01), 2 units of FFP (range 0–6; vs 12, p=0.04), and 5 units of platelets (range 0–10; vs 19, p=0.02). In one patient outlier, who had liver, spleen, kidney, pelvic and long bone fractures, the effect of rFVIIa was attenuated by surgical washout; INR correction and bleeding cessation were short-lived. The overall mortality in this series was 25% (2/8, including one patient whose care was withdrawn on hospital day 15 at the family’s request); this compares favorably to the 40%–50% mortality quoted in massively transfused trauma patients. There were no thromboembolic complications in this group of patients (myocardial infarction, stroke, and extremity thrombosis were specifically sought in all cases). Of note, during this time, 2 other patients were considered for rFVIIa by the trauma team, but additional blood component therapy as recommended by hematology consultation led to bleeding cessation.
Discussion: Low-dose rFVIIa (on the order of 20 μg/kg) used after appropriate blood component resuscitation appears to correct the coagulopathy of massive transfusion in critically injured blunt trauma patients. In this setting, rFVIIa can be very cost-effective. Collaboration between the trauma team and hematology or transfusion medicine specialist is important to guide the timing, dosing, and laboratory monitoring of rFVIIa.