Emergent Reversal of Antithrombotics and Treatment of Life-Threatening Bleeding from Coagulopathies: A Clinical Review.

BACKGROUND: Reversal of antithrombotic agents and treatment of life-threatening bleeding episodes from coagulopathies can be a stressful scenario for clinicians, especially when the selection of treatment options should occur quickly. Understanding the options available for these agents requires emergency physicians to be familiar with the current data surrounding new therapies and dosing strategies for the treatment of bleeding from reversible and nonreversible antithrombotics and coagulopathic conditions. OBJECTIVE: To provide quick resource guides for the reversal of major or life-threatening bleeding caused by antithrombotic agents or in the setting of coagulopathies. METHODS: A literature search for articles published through September 2021 related to antithrombotic reversal and treatment of acute bleeding from coagulopathies was conducted using the PubMed clinical database. Selected articles were used to generate 5 guidance tables in this clinical review. DISCUSSION: Four guidance tables for how to treat major or life-threatening bleeding from antithrombotic agents and 1 table for how to manage life-threatening bleeding for coagulopathies are presented as a quick reference tool for the emergency physician. Additional information on upcoming reversal agents and possible treatment options are provided herein. CONCLUSIONS: In this clinical review, a series of 5 tables were created to provide quick and comprehensive guidance for the emergency physician when treating major or life-threatening bleeding caused by antithrombotic agents or coagulopathies. © 2022 Elsevier Inc.

Development of a Pharmacist-Led Opt-Out Cessation Treatment Protocol for Combustible Tobacco Smoking Within Inpatient Settings.

Background: Although people who smoke cigarettes are overrepresented among hospital inpatients, few are connected with smoking cessation treatment during their hospitalization. Training, accountability for medication use, and monitoring of all patients position pharmacists well to deliver cessation interventions to all hospitalized patients who smoke. Methods: A large Midwestern University hospital implemented a pharmacist-led smoking cessation intervention. A delegation protocol for hospital pharmacy inpatients who smoked cigarettes gave hospital pharmacists the authority to order nicotine replacement therapy (NRT) during hospitalization and upon discharge, and for referral to the Wisconsin Tobacco Quit Line (WTQL) at discharge. Eligible patients received the smoking cessation intervention unless they actively refused (ie, "opt-out"). The program was pilot tested in phases, with pharmacist feedback between phases, and then implemented hospital-wide. Interviews, surveys, and informal mechanisms identified ways to improve implementation and workflows. Results: Feedback from pharmacists led to changes that improved workflow, training and patient education materials, and enhanced adoption and reach. Refining implementation strategies across pilot phases increased the percentage of eligible smokers offered pharmacist-delivered cessation support from 37% to 76%, prescribed NRT from 2% to 44%, and referred to the WTQL from 3% to 32%. Conclusion: Hospitalizations provide an ideal opportunity for patients to make a tobacco quit attempt, and pharmacists can capitalize on this opportunity by integrating smoking cessation treatment into existing inpatient medication reconciliation workflows. Pharmacist-led implementation strategies developed in this study may be applicable in other inpatient settings.

Evaluation of a Fixed-Dose Regimen of 4-Factor Prothrombin Complex Concentrate for Warfarin Reversal.

BACKGROUND: Fixed-dose (FD) regimens of 4-factor prothrombin complex concentrate (4F-PCC) may be effective for the emergent reversal of warfarin; however, the optimal dosing is unknown. Our institution transitioned to a FD regimen of 1000 or 2000 units of 4F-PCC based on indication. OBJECTIVE: The purpose of this study is to report our experience with FD 4F-PCC compared with a historical weight-based dosing cohort for warfarin reversal. METHODS: A retrospective analysis was conducted for 3 groups: central nervous system (CNS) bleeds regardless of international normalized ratio (INR), non-CNS bleeds with an initial INR ≤6, and non-CNS bleeds with an initial INR ≥6.1. The primary outcome of the study was achievement of the target INR. RESULTS: There were 54 patients with a CNS bleed, 153 with a non-CNS bleed and INR ≤6, and 19 with a non-CNS bleed and INR ≥6.1. In the CNS bleeding group, weight-based and FD achieved target INR 79.4% and 70% (P = 0.52). In the INR ≥6.1 non-CNS bleeding group, weight-based and FD achieved target INR 100% and 70% (P = 0.21). In the INR ≤6 non-CNS bleeding group, weight-based and FD achieved target INR 86.4% and 57.5% (P = 0.0002). CONCLUSION AND RELEVANCE: An FD strategy of 2000 units for warfarin reversal for CNS bleeds or INR ≥6.1 was comparable to weight-based dosing. The FD strategy of 1000 units for INR ≤6 achieved target INR less often than weight-based dosing. Application of findings suggest that higher doses may be needed to achieve target INR.

Electronic clinical decision support to facilitate a change in clinical practice: Small details can make or break success.

BACKGROUND: The use of electronic clinical decision support (CDS) is becoming common to change historically common clinical practices considered outdated by current guidelines. Preimplementation design of CDS tools is key to their success in changing clinical behaviors. Unfortunately, there are no established protocols for CDS tool development, and CDS failure can result from even small design flaws. This paper describes an example of a design oversight and how correction resulted in CDS success. STUDY DESIGN AND METHODS: We performed a retrospective review of compliance with a CDS tool to encourage the use of prothrombin complex concentrate over plasma transfusion for the emergent reversal of warfarin. We identified a potential design flaw, made the necessary modifications, and repeated the compliance review. RESULTS: After CDS, plasma orders declined by 150 units/mo; however, 48% of orders placed for non-warfarin coagulopathy were still for warfarin reversal. Hospital-wide, this noncompliance was 36% and was 80% in the emergency department. By simply relocating the qualifier "NOT on warfarin" from the end to the beginning of the order, noncompliance for warfarin reversal was reduced to 5% (P < .0001 by chi-square). CONCLUSIONS: The successful use of electronic clinical decision support in the electronic medical record can depend on optimal design. Missing even small design elements such as the positioning of key terms within the tool can result in an ineffective CDS. Important design strategies to avoid poor performance are discussed as they relate to the CDS tool we describe.

Pharmacist involvement in clinical assessment and laboratory testing for heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a rare adverse drug reaction. The anti-PF4 antibody assay (ELISA) is utilized to assist in the clinical evaluation of HIT due to its high negative predictability and wide-spread availability. However, it also associated with false positive results. The 4T score can assist in predicting an individual's risk for HIT and the need for further laboratory testing. This was a single-center prospective observational cohort study. Orders for HIT testing were sent via page to a clinical pharmacist to calculate a 4T score. If low risk, the pharmacist contacted the ordering prescriber to recommend discontinuation of laboratory testing. During the study, a clinical support tool was implemented to assist prescribers with ordering HIT tests. The study was divided into a pharmacist intervention group and a control group. A total of 303 pages were received. One hundred nine were missed due to unavailability of the pharmacist at time of page. A pharmacist reviewed 194 pages and intervened on 132. One hundred seven were scored as low risk, 70 as intermediate risk and 9 as high risk. Pharmacist intervention resulted in discontinuing 64 ELISA and 11 serotonin release assay tests. The clinical support tool resulted in a yearly decrease of HIT testing by 27%. Laboratory cost savings totaled $11,000 but did not include avoidance of laboratory technician or drug cost. Pharmacist involvement in the clinical assessment of HIT and the use of a support tool resulted in the reduction of HIT tests in low risk patients.

Analysis of anticoagulant prescribing in non-valvular atrial fibrillation and development of a clinical tool for guiding anticoagulant selection.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States. Traditionally, warfarin has been used to prevent the occurrence of stroke in intermediate-to-high risk patients. Target-specific oral anticoagulants (TSOACs) have become a favorable alternative; however, recommendations for differentiating between the available TSOACs were lacking within the 2012 CHEST guidelines. The objective of this retrospective, observational study was to identify current anticoagulation prescribing habits in patients admitted with new-onset AF, and evaluate the appropriateness of discharge therapy based on national guidelines. Additionally, a practice guideline was created for use at our institution to stratify appropriate use of TSOACs. Patients were included if they were at least 18 years old and were admitted with a primary diagnosis of new-onset, non-valvular AF between July 1, 2012 and June 30, 2013. CHADS2, CHA2DS2VASc, and HAS-BLED scores were calculated based on patient data. Between July 2012 and June 2013, 143 patients were included in the study. The average CHADS2 score was 1.7, the average CHA2DS2VASc score was 3.0, and the average HAS-BLED score was 2.4. The use of no antithrombotics decreased as the CHA2DS2VASc score increased, aspirin use stayed consistent across risk groups, warfarin use increased as the CHA2DS2VASc score increased, and TSOAC use decreased with increasing CHA2DS2VASc score. A total of 34 % of study patients were prescribed inappropriate treatment upon discharge, based on national guidelines. This study demonstrated that patients admitted to our hospital were prescribed appropriate therapy the majority of the time; however, 34 % were prescribed inadequate antithrombotic therapy compared to current practice guidelines given their CHA2DS2VASc score. The development of an institution-specific guideline stratifying appropriate use of anticoagulation in this population may increase adherence to national guideline recommendations.

Development of a Medication-Use Evaluation Template for Andexanet Alfa in the Reversal of Anticoagulation With Factor Xa Inhibitors.

Medication-use evaluations are meant to ensure that medication-use processes are consistent with prevailing standards of care, assure optimal use of therapy, and reduce the risk of medication-related problems. Reversal agents for direct oral anticoagulants are a worthy focus for medication-use evaluations for reasons of efficacy, safety, and cost. A multidisciplinary team of experts developed 2 medication-use evaluation templates illustrating the application of professional society guidelines to the appropriate use of andexanet alfa.

Reengaging patients with forgotten filters through an institutional multidisciplinary approach.

OBJECTIVE: The aim of the present study was to evaluate the outcomes of a hospital-wide multidisciplinary initiative to reengage and manage patients with unretrieved chronic indwelling inferior vena cava (IVC) filters placed at a large tertiary care center, who had been lost to follow-up. METHODS: We performed a retrospective review of outcomes from a completed multidisciplinary quality improvement project. The quality improvement project identified and contacted (via letter) patients with chronic indwelling IVC filters placed at a single tertiary care center from 2008 to 2016 who were alive and without evidence of filter retrieval in the medical records. A total of 316 eligible patients were mailed a letter regarding their chronic indwelling IVC filter and the updated recommendations regarding IVC filter removal. The letter included institutional contact information, and all the patients who responded were offered a clinic visit to discuss potential filter retrieval. In the retrospective review, we assessed the outcomes of the quality improvement project, including the patient response rate, follow-up clinic visits, new imaging studies generated, retrieval rate, procedural success, and complications. The patient demographics and filter characteristics were collected and evaluated for correlations with the response and retrieval rates. RESULTS: The patient response rate to the letter was 32% (101 of 316). Of the 101 patients who responded, 72 (71%) were seen in clinic and 59 (82%) underwent new imaging studies. Using standard and advanced techniques, 34 of 36 filters after a median dwell time of 9.4 years (range, 3.3-13.3 years) were successfully retrieved (94% success rate). The patients with a documented IVC filter complication were more likely to respond to the letter (odds ratio, 4.34) and undergo IVC filter retrieval (odds ratio, 6.04). No moderate or severe procedural complications occurred during filter retrieval. CONCLUSIONS: An institutional, multidisciplinary quality initiative successfully identified and reengaged patients with chronic indwelling IVC filters who had been lost to follow-up. The filter retrieval success rate was high and procedural morbidity low. Institution-wide efforts to identify and retrieve chronic indwelling filters are feasible.

Antithrombotic selection in patients undergoing transcatheter aortic valve replacement.

PURPOSE: Clinical controversy regarding the most appropriate antithrombotic regimen after transcatheter aortic valve replacement remains. Current evidence, guidelines, and recommendations are discussed. SUMMARY: Antithrombotic selection following transcatheter aortic valve replacement depends on a variety of patient-specific factors. For patients without a preexisting indication for anticoagulation, initial trials employed dual antiplatelet therapy as the postprocedural therapy of choice. Newer studies in this patient population, however, suggest single antiplatelet therapy reduces bleeding events without sacrificing ischemic protection. In patients with a preexisting indication for anticoagulation, warfarin plus single antiplatelet therapy, as opposed to triple antithrombotic therapy, offered similar ischemic protection while reducing clinically significant bleeding. Warfarin monotherapy was associated with a further reduction in bleeding events. One trial demonstrated the safety and efficacy of using apixaban in patients with concomitant atrial fibrillation; however, routine use of rivaroxaban increased adverse cardiac and bleeding events, leaving the utility of direct-acting oral anticoagulants in question. CONCLUSION: Available evidence and current guidelines point to a lack of consensus regarding antithrombotic selection after transcatheter aortic valve replacement. Patient-specific factors and comorbidities must be considered when tailoring therapy, with an emphasis on balancing thrombotic and bleeding risks.

Improving Warfarin Management Within the Medical Home: A Health-System Approach.

BACKGROUND: Anticoagulation clinics have been considered the optimal strategy for warfarin management with demonstrated improved patient outcomes through increased time in therapeutic international normalized ratio (INR) range, decreased critical INR values, and decreased anticoagulation-related adverse events. However, not all health systems are able to support a specialized anticoagulation clinic or may see patient volume exceed available anticoagulation clinic resources. The purpose of this study was to utilize an anticoagulation clinic model to standardize warfarin management in a primary care clinic setting. METHODS: A warfarin management program was developed that included standardized patient assessment, protocolized warfarin-dosing algorithm, and electronic documentation and reporting tools. Primary care clinics were targeted for training and implementation of this program. RESULTS: The warfarin management program was applied to over 2000 patients and implemented at 39 clinic sites. A total of 160 nurses and 15 pharmacists were trained on the program. Documentation of warfarin dose and date of the next INR increased from 70% to 90% (P <.0001), documentation occurring within 24 hours of the INR result increased from 75% to 87% (P <.0001), and monitoring the INR at least every 4 weeks increased from 71% to 83% (P <.0001) per patient encounter. Time in therapeutic INR range improved from 65% to 75%. CONCLUSION: Incorporating a standardized approach to warfarin management in the primary care setting significantly improves warfarin-related documentation and time in therapeutic INR range.