The Efficacy of Factor VIIa in Emergency Department Patients With Warfarin Use and Traumatic Intracranial Hemorrhage

Abstract

Objectives: The objective was to compare outcomes in emergency department (ED) patients with preinjury warfarin use and traumatic intracranial hemorrhage (tICH) who did and did not receive recombinant activated factor VIIa (rFVIIa) for international normalized ratio (INR) reversal.Methods: This was a retrospective before-and-after study conducted at a Level 1 trauma center, with data from 1999 to 2009. Eligible patients had preinjury warfarin use and tICH on cranial computed tomography (CT) scan. Patients before (standard cohort) and after (rFVIIa cohort) implementation of a protocol for administering 1.2 mg of rFVIIa in the ED were reviewed. Glasgow Coma Scale (GCS) score, Revised Trauma Score (RTS), Injury Severity Score (ISS), INR, and Marshall score were collected. Outcome measures included mortality, thromboembolic complications, and INR normalization.Results: Forty patients (median age = 80.5 years, interquartile range [IQR] = 63.5-85) were included (20 in each cohort). Age, GCS score, ISS, RTS, initial INR, and Marshall score were similar (p > 0.05) between the two cohorts. Survival was identical between cohorts (13 of 20, or 65.0%, 95% confidence interval [CI] = 40.8% to 84.6%). There were no differences in rate of thromboembolic complications in the standard cohort (1 of 20, 5.0%, 95% CI = 0.1% to 24.9%) than the rFVIIa cohort (4 of 20, 20.0%, 95% CI = 5.7% to 43.7%; p = 0.34). Time to normal INR was earlier in the rFVIIa cohort (mean = 4.8 hours, 95% CI = 3.0 to 6.7 hours) than in the standard cohort (mean = 17.5 hours, 95% CI = 12.5 to 22.6; p < 0.001). Conclusions:In patients with preinjury warfarin and tICH, use of rFVIIa was associated with a decreased time to normal INR. However, no difference in mortality was identified. Use of rFVIIa in patients on warfarin and tICH requires further study to demonstrate important patient-oriented outcomes.ACADEMIC EMERGENCY MEDICINE 2010; 17:244-251 ª

Pharmacologic interventions for reversing the effects of oral anticoagulants

“…The time to an INR less than 1.3 (i.e., normalization) was significantly shorter in the rFVIIa group than the standard treatment group (4.8 hours versus 17.5 hours, respectively, p < 0.001). 29 The time to surgery, which may reflect the time until the INR is reduced to a safe level, was lower in the rFVIIa group (5.6 hours; range, 2.1-9.2 hours) than the standard treatment group (74.6 hours; range, 70.5-219.7 hours), although the difference was not significant (p = 0.30). There was no difference between the two treatment groups in in-hospital mortality (35% for both groups, p = 1.0).…”

“…In a retrospective, nonrandomized study of 40 warfarin-treated adults with traumatic ICH and an INR greater than 1.3, the effectiveness of rFVIIa (mean dose, 17.7 ± 6.2 mg/kg) plus standard treatment for warfarin reversal (FFP with or without phytonadione) was compared with standard treatment alone. 29 All participants received other supportive measures or surgical interventions as needed.…”

“…injection plus (1) fourfactor PCC, (2) rFVIIa, or (3) aPCC will likely be effective for lowering the INR, according to the published literature. 29,[31][32][33][34][35] If surgery is needed but can be delayed for more than 24 hours, oral phytonadione alone may suffice for warfarin reversal based on the pharmacodynamics of vitamin K.…”

Developing a management plan for oral anticoagulant reversal

“…20,21 Data are available suggesting that rFVIIa doses as low as 1-2 mg (i.e., 14-28 mg/kg for a 70-kg person) are effective for warfarin reversal using the INR as a surrogate endpoint. [22][23][24] The optimal rFVIIa dose and the impact on bleeding complications are uncertain. The onset of effect for reducing both bleeding and the INR appears to be rapid, with the lowest effective dose sought primarily because of concerns about thrombosis.…”

A retrospective case control study of recombinant factor VIIa in patients with intracranial haemorrhage caused by trauma

“…In reviewing the literature (Table II), we found 10 reports about the use of rFVIIa in trauma patients with traumatic intracranial haemorrhage (Bartal et al, 2007;Kluger et al, 2007;Narayan et al, 2008;Stein et al, 2008Stein et al, , 2009Sutherland et al, 2008;Zaaroor et al, 2008;McQuay et al, 2009;Brown et al, 2010;Nishijima et al, 2010). Four were single-armed studies, four were cohort studies, one was a dose-finding study, and the other a sub-group of a randomized clinical trial.…”