Efficacy of 4-Factor Prothrombin Complex Concentrates in Factor Xa Inhibitor-Associated Intracranial Bleeding.

BACKGROUND/OBJECTIVE: Intracranial bleeding (ICB) is a feared complication of systemic anticoagulation. Factor Xa inhibitors (FXaI) are used frequently due to their improved safety profile and predictable kinetics. Andexanet alfa was recently approved for emergent reversal of FXaI agents but was not compared formally to 4-Factor Prothrombin Complex Concentrates (4FPCC) which are the current standard of care in many centers. The objective of this study is to formally evaluate the hemostatic efficacy of 4FPCC in patients with FXaI-associated ICB. METHODS: We performed a retrospective cohort study of patients receiving 4FPCC for the reversal of a FXaI in the setting of acute ICB. Hemostatic efficacy was adjudicated via evaluation of post-4FPCC CT scan using the criteria closely mirroring those outlined in Annexa-4 (excellent < 20% expansion, good > 20% but ≤ 35% expansion, poor > 35% expansion). Each image was reviewed by two neurointensivist attendings for grading. Mortality was assessed until date of discharge. Charts were screened for thrombotic events out to 30 days post-4FPCC administration. RESULTS: A total of 59 patients were included in the final analysis. The mean age in years was 78.5 ± 10.9 and 56% were male. Apixaban was the most common FXaI prescribed at the time of presentation (67.8%). Most patients were on FXaI therapy for stroke prevention in the setting of atrial fibrillation (81.3%). Median Glasgow Coma Scale at presentation was 15(IQR 12-15), with the most frequently presenting ICB type being intracerebral hemorrhage (52.5%). The mean dose of 4FPCC prescribed was 46.6 (± 8.2) units/kg. Of those receiving 4FPCC for FXaI ICB, 88% were graded as having an excellent or good hemostatic outcome with excellent interrater reliability. Survival was high at 89.8%, and thrombotic events were seen in seven patients (11.9%). CONCLUSION: 4FPCC appears to be an effective and safe option for FXaI-associated ICB with outcomes comparable to andexanet alfa. A formal prospective evaluation of this strategy versus andexanet alpha including cost analysis is warranted.

Thrombolytic Therapy in Wake-Up Stroke Patients.

OBJECTIVE: The aim of the study is to review existing and ongoing trial data on wake-up stroke (WUS) patients for thrombolytic therapy. METHODS: A literature search was conducted in PubMed (conception-October 2016) using the terms wake-up stroke, acute ischemic stroke, wake-up thrombolysis, computed tomography imaging in wake-up stroke, and magnetic resonance imaging in wake-up stroke. Ongoing trials were found using the ClinicalTrials.gov website. RESULTS: The search yielded 61 articles in PubMed and 7 ongoing trials. After removing duplicate/irrelevant articles, 33 articles and relevant references were reviewed; of these, 6 articles and 3 ongoing trials were included. Two retrospective studies evaluating the characteristics between WUS and known-onset stroke were identified; the only significant difference between groups was the ability to receive treatment with tissue plasminogen activator (tPA). One study suggested that perfusion brain imaging may be useful to identify patients that may benefit from tPA. In addition, 3 studies have evaluated WUS treatment; all used different methods to identify potential patients. Two of 3 studies showed that treatment with tPA is associated with better outcomes when controlling for baseline National Institutes of Health Stroke Scale. No difference in safety outcomes was seen between groups for all 3 studies. CONCLUSIONS: Available data suggest promising strategies to identify WUS patients who may benefit from thrombolysis. Once on-going trials are complete, there may be sufficient information to redefine tPA eligibility for previously excluded patients.

Evaluation of a Pharmacy-Managed Pharmacokinetic Dosing Program.

PURPOSE: The objective of this study was to determine the impact of a pharmacy-managed pharmacokinetic dosing program on appropriate dosing of famotidine, enoxaparin, and ketorolac. METHODS: A large community teaching hospital implemented a pharmacy-managed pharmacokinetic dosing program for famotidine, enoxaparin, and ketorolac. Subjects were included if they received famotidine and had a creatinine clearance (CrCl) of <50 mL/min; received therapeutic enoxaparin and had a CrCl of <30 mL/min; or received ketorolac and had a CrCl <30 mL/min, age > 65 years or weight <50 kg. RESULTS: One hundred and forty-six patients were included in the preimplementation group (famotidine [n = 50], enoxaparin [n = 46], and ketorolac [n = 50]) and 143 patients were included in the postimplementation group (famotidine [n = 50], enoxaparin [n = 43], and ketorolac [n = 50]). In all, 66% of patients were dosed appropriately in the preimplementation group (famotidine 28%, enoxaparin 85%, and ketorolac 86%) compared to 94% in the postimplementation group (famotidine 92%, enoxaparin 95%, and ketorolac 94%), P < .001. CONCLUSION: Implementation of a pharmacy-managed pharmacokinetic dosing program significantly improved appropriate dosing of famotidine, enoxaparin, and ketorolac. These findings could justify expansion of pharmacist autonomy through institution-approved, pharmacy-managed programs for other medications to improve appropriate dosing. Analyses specifically evaluating patient-oriented or financial outcomes may provide additional support for expansion.