Emergent Warfarin Reversal With Fixed-Dose 4-Factor Prothrombin Complex Concentrate.

BACKGROUND: Four-factor prothrombin complex concentrate (4FPCC) is used for emergent warfarin reversal, but dosing remains controversial. Following approval, further studies have evaluated a variety of fixed-dose regimens. The studies utilized lower doses as compared with package insert dosing and provided data in regard to efficacy, safety, and cost savings. Further data are needed, however, to determine which fixed-dose regimen provides optimal efficacy and safety for emergent warfarin reversal. OBJECTIVES: The purpose of this study is to evaluate the efficacy, safety, and cost-savings of a fixed-dose 4FPCC protocol. METHODS: This multicentered, retrospective chart review of adult patients requiring 4FPCC for emergent warfarin reversal utilized a fixed-dose regimen of 1500 units. The 2 primary outcomes were the proportion of patients who achieved a post-4FPCC international normalized ratio (INR) of ≤1.5 and ≤2. Secondary outcomes included thrombotic events within 7 days of 4FPCC administration and survival to discharge. A cost analysis was also performed to identify potential cost savings. RESULTS: Of the 64 patients included, 44 (68.8%) achieved a post-4FPCC INR ≤1.5, and 61 (95.3%) achieved a post-4FPCC INR ≤2.0. No thrombotic events were reported; 55 (85.9%) patients survived to hospital discharge. More than $1000 was saved per patient via utilization of the fixed-dose protocol. CONCLUSION AND RELEVANCE: A fixed-dose of 1500 units of 4FPCC successfully achieved a target INR of ≤1.5 in the majority of patients and resulted in no thrombotic events. This study adds to the data evaluating alternative 4FPCC dosing regimens in comparison to package insert recommended dosing.

Guideline adherence for the management of emergency department patients with febrile neutropenia and no infection source: Is there room for improvement?

INTRODUCTION: Febrile neutropenia is an oncologic emergency associated with significant morbidity and mortality. The objective of our study was to assess guideline adherence and clinical outcomes associated with the management of high- and low-risk febrile neutropenia patients presenting to the emergency department. METHODS: A retrospective observational cohort study was conducted at a 60,000-visit emergency department at an academically-affiliated tertiary referral hospital. Patients were identified as low- or high-risk using the guideline-recommended Multinational Association for Supportive Care in Cancer score. The primary outcome was the proportion of cases in which the management was concordant with applicable febrile neutropenia guidelines. Guideline adherence was defined as hospital admission and intravenous antimicrobial therapy for high-risk patients and discharge home with oral antimicrobial therapy for low-risk patients. Secondary outcomes included appropriate vancomycin administration, hospital length of stay, rates of acute kidney injury, in-hospital Clostridium difficile infection rates, and 30-day mortality. RESULTS: Of the 237 patients included, 94 (39.7%) were low-risk patients and 143 (60.3%) were high-risk patients. Guideline adherence occurred in 96.8% of high-risk patients and 0.4% of low-risk patients. Mean hospital length of stay of the low-risk group was 5 ± 5.0 days compared to 7.2 ± 7.3 days in the high-risk group. Vancomycin was often inappropriately given in 69.5% of high-risk patients. Clostridium difficile occurred in 15 (10.3%) adherent and 4 (4.4%) non-adherent patients. By 30 days, 4 (4.3%) low-risk and 15 (10.7%) high-risk patients died. CONCLUSION: Adherence to the febrile neutropenia guidelines was low resulting in unnecessary hospital admissions of low-risk patients and frequent over-prescription of empirical vancomycin.