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.

Utilization and safety of off-label prothrombin complex concentrate (four-factor prothrombin complex concentrate) in a surgical population.

The aim of this study is to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, surgical patient population at an academic, tertiary care center. This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between 1 January 2017 and 30 September 2022 for a surgical or peri-procedural indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, assessed by subsequent blood product administration and hemoglobin and hematocrit reduction. Secondary outcomes included an assessment of thrombotic events within 30 days post-4F-PCC administration, in-hospital mortality, and the length of hospital stay. A total of 71 patients met the inclusion criteria, with 61 patients receiving 4F-PCC for cardiac surgery and 10 patients for other intraoperative or peri-procedural indications. The mean total 4F-PCC dose was 25.0 U/kg. For the primary outcome of hemostatic efficacy, 81% of patients had excellent hemostasis; however, blood product administration was reported in 95.8% of patients post-4F-PCC. Thromboembolic events occurred in 10 (14.1%) patients and 21.1% of patients expired prior to discharge in the total cohort. Off-label 4F-PCC use in nonanticoagulated patients is reported despite a lack of robust guidance for use. Following 4F-PCC administration, hemostatic efficacy based on hemoglobin and hematocrit changes was observed; however, blood product use was frequent, and 4F-PCC administration was not without risks, including thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism, and stroke. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.

Utilization and safety of off-label prothrombin complex concentrate (4F-PCC) in a nonsurgical population.

The aim of this study was to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, nonsurgical patient population at an academic, tertiary care center. This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between January 1, 2017, and September 30, 2022, for a nonsurgical indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, and secondary outcomes included an assessment of blood product administration, thrombotic events within 30 days post4F-PCC administration, in-hospital mortality, and the length of hospital stay. A total of 59 patients met the inclusion criteria, and 10 patients received 4F-PCC for coagulopathy associated with liver disease, 34 for intracranial hemorrhage (ICH), and 15 for other indications. For the primary outcome of hemostatic efficacy, 17 non-ICH patients (85%) had achieved hemostasis post-4F-PCC, and among the ICH patient population, 18 (64%) did not show expansion on repeat CT post4F-PCC, suggesting hemostasis. Blood product and hemostatic agent usage was frequent, with 72.9% of patients requiring products post-4F-PCC. Acute thromboembolic events occurred in six patients (10.2%), and in-hospital mortality occurred in 55.9% of patients. Off-label 4F-PCC use is common despite a lack of robust guidance for use. Following 4F-PCC administration, blood product use was frequent, the incidence of in-hospital mortality was high, and thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke were reported. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.

Digital dashboards for direct oral anticoagulant surveillance, intervention and operational efficiency: uptake, obstacles, and opportunities.

Direct oral anticoagulants (DOAC) are the most widely prescribed oral anticoagulants in the United States. Despite advantages over warfarin, system-level improvements are needed to optimize outcomes. While Veterans Health Administration and others have described successful DOAC management dashboard implementation, the extent of use nationally is unknown. A survey of Anticoagulation Forum's members was conducted to assess access to digital tools available within a dashboard and to describe implementation models. An Expert Forum was subsequently convened to identify barriers to dashboard development and adoption. Responses were received from 340 targeted recipients (8.5% of invitees). Only a minority of inpatient (25/52, 48.1%) and outpatient (47/133, 35.3%) respondents outside of Veterans Health Administration were able to generate rosters of DOAC users on-demand, and fewer had the ability to digitally display key clinical data elements, identify drug-related problems, document interventions, or generate reports. The lack of regulatory requirements regarding Anticoagulation Stewardship was identified by the Expert Forum as the major barrier to widespread development of digital tools for improved anticoagulation management. While some health systems have demonstrated the feasibility of DOAC dashboards and described their impact on quality and efficiency, these tools do not appear to be widely available in the United States apart from Veterans Health Administration. The lack of regulatory requirements for Anticoagulation Stewardship may be the primary barrier to the development of digital resources to better manage anticoagulants. Efforts to secure regulatory requirements for Anticoagulation Stewardship are needed, and evidence of improvements in clinical and financial outcomes through DOAC dashboard use will likely bolster such efforts.

Digital dashboards for oral anticoagulation management: a literature scoping review.

This scoping review summarizes the extent and characteristics of the published literature describing digital population management dashboards implemented to improve the quality of anticoagulant management. A standardized search protocol was executed to identify relevant manuscripts published between January 1, 2015 and May 31, 2022. The resulting records were systematically evaluated by multiple blinded reviewers and the findings from selected papers were evaluated and summarized. Twelve manuscripts were identified, originating from 5 organizations within the US and 2 from other countries. The majority (75%) described implementation in the outpatient setting. The identified papers described a variety of positive results of dashboard use, including a 24.5% reduction of questionable direct oral anticoagulant dosing in one organization, a 33.3% relative improvement in no-show appointments in an ambulatory care clinic, and a 75% improvement in intervention efficiency. One medical center achieved a 98.4% risk-appropriate venous thromboembolism risk prophylaxis prescribing rate and 40.6% reduction in anticoagulation-related adverse event rates. The manuscripts primarily described retrospective findings from single-center dashboard implementation experiences. Digital dashboards have been successfully implemented to support the anticoagulation of acute and ambulatory patients and available manuscripts suggest a positive impact on care-related processes and relevant patient outcomes. Prospective studies are needed to better characterize the implementation and impact of dashboards for anticoagulation management. Published reports suggest that digital dashboards may improve the quality, safety, and efficiency of anticoagulation management. Additional research is needed to validate these findings and to understand how best to implement these tools.

Cerebral venous sinus thrombosis associated with SRA-negative heparin-induced thrombocytopenia: case report.

BACKGROUND: There are very few documented reports in literature of cerebral venous sinus thrombosis (CVST) caused by immune-mediated heparin-induced thrombocytopenia (HIT). Further, there are very few reports of false negative serotonin release assays (SRAs) when testing for immune-mediated HIT. CASE PRESENTATION: We present a case of a 60- year-old male with recent unfractionated heparin administration for venous thromboembolism prophylaxis, an elevated 4T score of 5 and acute CVST in which immune-mediated HIT was suspected. The enzyme-linked immunosorbent assay (ELISA) screening assay was positive for PF4 antibodies and subsequent reflexive SRA testing was negative. However, given the clinical picture, a false-negative SRA was suspected (and eventually confirmed), prompting use of the alternative PF4-dependent p-selectin expression assay (PEA) which was confirmed to be positive. The patient was successfully managed with a bivalirudin infusion and eventually transitioned to apixaban. CONCLUSION: It is uncommon for immune-mediated HIT with thrombosis to manifest as CVST. Similarly, false-negative SRA is uncommon in immune-mediated HIT. Take-away lessons from our case report include considering HIT in CVST patients with an elevated 4T score and considering the entire clinical picture and degree of suspicion for HIT when interpreting negative HIT testing results. The PEA, in conjunction with the 4Ts score, may be considered as an alternate diagnostic assay for HIT.

Impact of Hospital-based Multidisciplinary Anticoagulation Stewardship Programs.

Antithrombotic therapies, especially anticoagulants, are high-risk medications with increased potential for adverse events. The development and implementation of a well-functioning, designated, multidisciplinary anticoagulation stewardship program (MASP), tailored to each hospital-center's needs, has the primary objectives of improving patient-centered outcomes, minimizing undesirable anticoagulation-related adverse events and minimizing hospital length of stay (LOS) and other patient-related costs. Such stewardship programs are pivotal in supporting busy clinicians with consultation on challenging clinical case scenarios, ensuring appropriate use of valuable healthcare resources, achieving compliance with anticoagulant-associated accreditation standards, and positively impacting patient-specific morbidity/mortality outcomes. Herein, we review and discuss the critical need for antithrombosis stewardship and the benefit of formalized MASP in optimizing use of antithrombotic therapies.

Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: updated clinical guidance from the anticoagulation forum.

Thromboembolism is a common and deadly consequence of COVID-19 infection for hospitalized patients. Based on clinical evidence pre-dating the COVID-19 pandemic and early observational reports, expert consensus and guidance documents have strongly encouraged the use of prophylactic anticoagulation for patients hospitalized for COVID-19 infection. More recently, multiple clinical trials and larger observational studies have provided evidence for tailoring the approach to thromboprophylaxis for patients with COVID-19. This document provides updated guidance for the use of anticoagulant therapies in patients with COVID-19 from the Anticoagulation Forum, the leading North American organization of anticoagulation providers. We discuss ambulatory, in-hospital, and post-hospital thromboprophylaxis strategies as well as provide guidance for patients with thrombotic conditions who are considering COVID-19 vaccination.

Antithrombosis stewardship efforts to de-escalate inappropriate combined therapy in outpatient clinics.

Antithrombotic therapies include anticoagulants and antiplatelet agents. It is increasingly recognized that combined dual antithrombotic (DAT, which consists of an oral anticoagulant and a single antiplatelet) and triple antithrombotic therapies (TAT, which consists of an oral anticoagulant and two antiplatelets) increase bleeding risk. Additionally, the benefit of aspirin for primary prevention has been called into question by a number of randomized controlled trials over the last few years. As such, several recent clinical trials have explored de-escalated antithrombotic regimens that have resulted in less bleeding with similar efficacy. Our study was a retrospective, observational investigation assessing the effect of a systematic antithrombosis stewardship intervention implemented in outpatient, pharmacy-driven antithrombosis clinics on the number of patients receiving potentially inappropriate combined antithrombotic therapy. Pharmacists identified anticoagulation patients on concomitant antiplatelet therapy, assessed for appropriateness, and performed interventions if needed. Of the 875 patients included, 261 (29.8%) were on combined antithrombotic therapy, 48 (18.4%) of which were deemed inappropriate at baseline. By the end of the intervention period, 45 (93%) of these patients had a de-escalation in combined therapy (p < 0.001). We found that a systematic de-escalation protocol led to a significant reduction in patients on inappropriate combined antithrombotic therapy.

Perioperative consultative hematology: can you clear my patient for a procedure?

Periprocedural management of antithrombotics is a common but challenging clinical scenario that renders patients vulnerable to potential adverse events such as bleeding and thrombosis. Over the past decade, periprocedural antithrombotic approaches have changed considerably with the advent of direct oral anticoagulants (DOACs), as well as a paradigm shift away from bridging in many warfarin patients. Successfully navigating this high-risk period relies on a number of individualized patient assessments conducted within a framework of standardized, systematic approaches. It also requires a thorough understanding of antithrombotic pharmacokinetics, multidisciplinary coordination of care, and comprehensive patient education and empowerment. In this article, we provide clinicians with a practical, stepwise approach to periprocedural management of antithrombotic agents through case-based examples of relevant clinical scenarios.

Ciraparantag, an anticoagulant reversal drug: mechanism of action, pharmacokinetics, and reversal of anticoagulants.

Ciraparantag, an anticoagulant reversal agent, is a small molecule specifically designed to bind noncovalently by charge-charge interaction to unfractionated heparin and low-molecular-weight heparin. It shows binding characteristics that are similar to those of direct oral anticoagulants (DOACs). A dynamic light-scattering methodology was used to demonstrate ciraparantag's binding to the heparins and DOACs and its lack of binding to a variety of proteins including coagulation factors and commonly used drugs. Ciraparantag reaches maximum concentration within minutes after IV administration with a half-life of 12 to 19 minutes. It is primarily hydrolyzed by serum peptidases into 2 metabolites, neither of which has substantial activity. Ciraparantag and its metabolites are recovered almost entirely in the urine. In animal models of bleeding (rat tail transection and liver laceration), a single IV dose of ciraparantag given at peak concentrations of the anticoagulant, but before the bleeding injury, significantly reduced the blood loss. Ciraparantag, given after the bleeding injury, also significantly reduced blood loss. It appears to have substantial ability to reduce blood loss in animal models in which a variety of anticoagulants are used and has potential as a useful DOAC reversal agent.

Risk-assessment models for VTE and bleeding in hospitalized medical patients: an overview of systematic reviews.

Multiple risk-assessment models (RAMs) for venous thromboembolism (VTE) in hospitalized medical patients have been developed. To inform the 2018 American Society of Hematology (ASH) guidelines on VTE, we conducted an overview of systematic reviews to identify and summarize evidence related to RAMs for VTE and bleeding in medical inpatients. We searched Epistemonikos, the Cochrane Database, Medline, and Embase from 2005 through June 2017 and then updated the search in January 2020 to identify systematic reviews that included RAMs for VTE and bleeding in medical inpatients. We conducted study selection, data abstraction and quality assessment (using the Risk of Bias in Systematic Reviews [ROBIS] tool) independently and in duplicate. We described the characteristics of the reviews and their included studies, and compared the identified RAMs using narrative synthesis. Of 15 348 citations, we included 2 systematic reviews, of which 1 had low risk of bias. The reviews included 19 unique studies reporting on 15 RAMs. Seven of the RAMs were derived using individual patient data in which risk factors were included based on their predictive ability in a regression analysis. The other 8 RAMs were empirically developed using consensus approaches, risk factors identified from a literature review, and clinical expertise. The RAMs that have been externally validated include the Caprini, Geneva, IMPROVE, Kucher, and Padua RAMs. The Padua, Geneva, and Kucher RAMs have been evaluated in impact studies that reported an increase in appropriate VTE prophylaxis rates. Our findings informed the ASH guidelines. They also aim to guide health care practitioners in their decision-making processes regarding appropriate individual prophylactic management.

Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum.

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes. While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic. It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients. Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients. Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience. The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19. We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

A cross-sectional survey evaluating transgender-related care education in United States pharmacy school curricula.

INTRODUCTION: The objectives of this study are to evaluate the extent of transgender-related care in current pharmacy school curricula, identify where transgender-related care is covered in the curriculum, describe how the content is delivered to pharmacy students, and review how student knowledge of transgender-related care is evaluated. METHODS: This cross-sectional study utilized an online survey of curricular contacts of 142 pharmacy schools in the United States. Survey questions regarding transgender-related care were presented as multiple choice, ranking, and free-response. The survey inquired about transgender-related care information taught, teaching methods, hours of education, and student assessment. RESULTS: Of the 66 schools that responded to the survey, 53% indicated that transgender-related education is a topic that is currently addressed somewhere within the curriculum. Twenty-two pharmacy schools incorporate this topic into the didactic curriculum, two into the experiential curriculum, and 10 into both didactic and experiential. Transgender-related care is only taught in the required curriculum of 41.2% of schools that responded to the survey. CONCLUSION: Transgender-related care education is taught to variable degrees throughout US doctor of pharmacy programs. This study should serve as a call to action to incorporate this necessary transgender-related care education and training into pharmacy curricula to effectively reduce health disparities among this population that is increasingly seeking care.

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum.

Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non-specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.

American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients.

BACKGROUND: Venous thromboembolism (VTE) is the third most common vascular disease. Medical inpatients, long-term care residents, persons with minor injuries, and long-distance travelers are at increased risk. OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about preventing VTE in these groups. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and adult patients. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 19 recommendations for acutely ill and critically ill medical inpatients, people in long-term care facilities, outpatients with minor injuries, and long-distance travelers. CONCLUSIONS: Strong recommendations included provision of pharmacological VTE prophylaxis in acutely or critically ill inpatients at acceptable bleeding risk, use of mechanical prophylaxis when bleeding risk is unacceptable, against the use of direct oral anticoagulants during hospitalization, and against extending pharmacological prophylaxis after hospital discharge. Conditional recommendations included not to use VTE prophylaxis routinely in long-term care patients or outpatients with minor VTE risk factors. The panel conditionally recommended use of graduated compression stockings or low-molecular-weight heparin in long-distance travelers only if they are at high risk for VTE.