Background:
Despite the wide use of warfarin therapy this drug is associated with the largest number of serious adverse event reports by the FDA with 86% of warfarin-associated bleeds resulting in serious outcomes, and 10% in fatal outcomes. The American College of Chest Physicians Evidence-Based Clinical Practice Guidelines recommend rapid reversal with 4-factor prothrombin complex concentrate (PCC) rather than plasma (FFP). Despite the benefits of PCCs over FFP, including immediate INR reversal via rapid, small infusion, these products are underused.
Purpose:
Our goal was to test the feasibility and impact on safety and effectiveness of step dose 4-factor PCC administration to patients taking warfarin with life/organ threatening bleeds. The protocol provided an initial fixed dose of PCC, followed by subsequent doses as needed (based on clinical response and INR). The initial dose administered was significantly lower than the package insert dose for most patients.
Description:
The protocol, approved by Pharmacy & Therapeutics and the Medical Board, was created by a multidisciplinary group: hematology, transfusion medicine (TM), pharmacy, trauma surgery, neurointensivists, and hospitalists. Innovative aspects include immediate release of PCC (1000 units for non-intracranial bleeds, 1500 units for intracranial hemorrhage (ICH)) for rapid administration after the first blood draw but prior to receiving results. Subsequent dosing was based on clinical status, INR response, and discussion with TM.
In the first three months since its implementation (August 2014), 26 patients received 4-factor PCC under the protocol. Half of these patients were male with mean age of 79 years. Seven were on antiplatelet therapy with aspirin, none were on clopidogrel. The most common reason for anticoagulation was atrial fibrillation (21/26), and the most common bleed type was ICH (20/26). Eight patients received FFP (2-6 units). Baseline INR ranged from 1.43 to >15, and all but 1 achieved INRs of <2 post PCC infusion. The exception had a baseline INR>15 and follow up INR of 2.05. Only two patients received subsequent PCC dosing. Eight patients died, and three were discharged to hospice. The death rate for ICH was 50%, comparable with the mortality rate reported in the literature. There was a 28% cost savings seen with upfront dosing.
Conclusions:
Our protocol sought to assess the practicality and impact of implementing a therapeutic intervention to improve safety and quality of care for vulnerable patients. Preliminary results in our relatively small sample suggest that a protocol using upfront PCC doses smaller than FDA recommendations can be effective in warfarin reversal, with significant cost savings. There were no identified adverse effects of this stepwise approach to rapid INR reversal and further assessment is ongoing to introduce the protocol to referring hospitals to expedite treatment in patients who require transfer.