Air Ambulance Delivery and Administration of Four‐factor Prothrombin Complex Concentrate Is Feasible and Decreases Time to Anticoagulation Reversal

Abstract

Objectives:The objective was to evaluate the feasibility, safety, and preliminary efficacy of four-factor prothrombin complex concentrate (4-factor PCC) administration by an air ambulance service prior to or during transfer of patients with warfarin-associated major hemorrhage to a tertiary care center for definitive management (interventional arm) compared to patients receiving 4-factor PCC following transfer by air ambulance or ground without 4-factor PCC treatment (conventional arm).Methods: This was a retrospective chart review of patients presenting to a large academic medical center. All patients presenting to the emergency department (ED) treated with 4-factor PCC from April 1, 2014, through June 30, 2016, were identified. For this study, only transfer patients with an International Normalized Ratio (INR) > 1.5 actively treated with warfarin were included. The primary outcome was the proportion of patients with an INR ≤ 1.5 upon tertiary care hospital arrival, and the secondary efficacy outcome was difference in time to achievement of INR ≤ 1.5. Additional safety and efficacy objectives included difference in thromboembolic complications, length of stay, intensive care unit length of stay, and inpatient mortality between groups.Results: Of the 72 included patients, a higher proportion of patients in the interventional group had an INR ≤ 1.5 on ED arrival (proportion difference = 0.82, 95% confidence interval = 0.64-0.92, p < 0.0001) and significantly reduced time to observed INR ≤ 1.5 (181 minutes vs. 541 minutes, p = 0.001). No differences were observed in thromboembolic complications or patient-centered outcomes with the exception of mortality, which was significantly higher in patients in the interventional group. This group was also observed to have lower Glasgow Coma Scale score and higher intubation rates prior to transfer and treatment.Conclusions: Dispatch of an air ambulance carrying 4-factor PCC with administration prior to transfer is feasible and leads to more rapid improvement in INR among patients with warfarin-associated major hemorrhage. F our-factor prothrombin complex concentrate (4-factor PCC) is a nonactivated agent that contains vitamin K-dependent coagulation factors II, VII, IX, and X and antithrombotics C and S. Four-factor PCC has been FDA approved for patients requiring the rapid reversal of anticoagulation and has been shown to be as clinically effective, or even superior, in its reversal of vitamin K antagonists within 30

Optimal Dosage and Administration Practices for Vitamin K Antagonist Reversal With 4-Factor Prothrombin Complex Concentrate

“… 67 Such early intervention has been shown to significantly increase the proportion of patients achieving a target INR of ≤1.5 from 3.7 upon ED arrival (proportion difference 0.8; p < 0.0001), and faster overall time to normalization (181 versus 541 minutes with no early intervention; p < 0.001). 63 Similarly, a retrospective cohort study comparing patients with warfarin-associated ICH who had transferred from a local community hospital (N = 177) or presented directly to the ED (N = 26), found the time to administration of 4F-PCC was longer in transferred patients (median difference -176 min; p≤0.001). However, the delay was not associated with worse patient outcomes, with no difference in hematoma expansion, hospital stay, or mortality.…”

“…This practice is currently quite rare, but could have a substantial impact. 63 Pre-hospital administration of 4F-PCCs by a mobile stroke unit, 64 air ambulance 63 or emergency retrieval service, 65 particularly in remote settings where access to definitive care may otherwise be unavailable or limited, 66 should also reduce door-to-needle time versus waiting until hospital presentation. 67 Such early intervention has been shown to significantly increase the proportion of patients achieving a target INR of ≤1.5 from 3.7 upon ED arrival (proportion difference 0.8; p < 0.0001), and faster overall time to normalization (181 versus 541 minutes with no early intervention; p < 0.001).…”

“…Time to treatment is also a key determinant of successful INR reversal and patient outcomes, and can be expedited by pre-hospital administration by mobile units or emergency services, and improvements in hospital logistics. 56 , 63 , 64 Logistical improvements could include point-of-care INR testing, 48 clinically appropriate administration of 4F-PCCs by ED doctors or pharmacists, 3 , 57 – 59 , 61 and adopting strategies to improve 4F-PCC access. 55 Implementation of institutional guidelines endorsing autonomous verification and dispensing of 4F-PCCs are associated with better patient outcomes, including INR reversal and hemostasis control, 3 , 57 – 59 as are guidelines providing clear recommendations on 4F-PCC dosing and administration practices, even if guidance contravenes label recommendations.…”

Prehospital Resuscitation

“…An ongoing trial is comparing addition of PCC to fibrinogen concentrate for in-hospital resuscitation of patients with TIC [117]. Prehospital data on PCC is limited to case reports and 1 small case series of 34 patients receiving PCC for pre-injury warfarin anticoagulation from a rural air medical transport service demonstrating reduced time to reversal of anticoagulation [118][119][120]. PCC appears to show promise in the prehospital environment for patients with known vitamin K antagonist anticoagulation, particularly in the setting of TBI; however, this requires further study given the lack of robust data and potential for thrombotic adverse events in TIC patients without pre-injury anticoagulation.…”

Location, Location, Location: The Rural–Urban Divide in Intracerebral Hemorrhage Mortality

“…Some rural institutions have started innovative initiatives to address a lack of resources. An example of such an initiative is air ambulance delivery of PCC from a tertiary center to resource-limited hospitals in rural Mississippi for expedited coagulopathy reversal [9]. While this is one example of an admirable single-institution effort to address a focused need on a relatively small scale, lasting and widespread efforts to increase access to high-quality care in rural communities require structural systems of care and policy changes.…”