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.

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.

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.

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.

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.

Defining Minimum Necessary Anticoagulation-Related Communication at Discharge: Consensus of the Care Transitions Task Force of the New York State Anticoagulation Coalition.

BACKGROUND: Anticoagulated patients are particularly vulnerable to ADEs when they experience changes in medical acuity, pharmacotherapy, or care setting, and resources guiding care transitions are lacking. The New York State Anticoagulation Coalition convened a task force to develop a consensus list of requisite data elements (RDEs) that should accompany all anticoagulated patients undergoing care transitions. METHODS: A multidisciplinary panel of 15 anticoagulation experts voluntarily completed an iterative Delphi process. Resources were disseminated and deliberated via remote technology, with consensus achieved via blinded electronic polling. RESULTS: The panel reached consensus on a list of 15 RDEs for anticoagulation communication at discharge (the ACDC List). Consensus was rapidly achieved by the full panel on 13 elements, while 3 (2 of which were combined into 1 element) required multiple iterations and achieved consensus with votes from 8 available panelists. The elements encompassed a range of factors, including drug use and indications, previous exposure and duration of therapy, recent drug exposure and laboratory results and expectations for subsequent administration, therapy goals, patient education and comprehension, and expectations for clinical management. Twelve of the elements are applicable to any anticoagulant, and 3 are specific to warfarin. CONCLUSION: The ACDC List identifies specific pieces of clinical information that a panel of anticoagulant experts agree should be communicated to downstream providers for all anticoagulated patients undergoing care transitions. Additional study is needed to objectively evaluate the ability of existing care systems to communicate the elements and to assess possible relationships between communication of the elements and clinical outcomes.

Peri-procedural antithrombotic management: time to burn the bridge?

Emerging evidence suggests the use of peri-procedural bridging during interruptions in warfarin therapy increases bleed risk without reducing thromboembolic events. We implemented a peri-procedural anticoagulant management risk assessment tool in a single, outpatient anticoagulation clinic within an academic teaching institution. In this retrospective, pre-post observational study, we evaluated adults who required an interruption in warfarin therapy for an invasive procedure. The primary outcome was the proportion of patients who received bridging prior to and following implementation of the tool. Secondary outcomes included major bleeding, clinically relevant non-major bleeding, thromboembolic events, and other surgical complications within 30 days of the index procedure. In total, 149 patients were included. Bridging was recommended in 60% of the pre-intervention group and in 39.3% of the post-intervention group (p = 0.012). There were no significant differences in the secondary outcomes between the groups. However, patients who received bridging had numerically more bleeding events than patients who did not (12.3 vs. 3.9%, p = 0.102), and patients who received therapeutic dose bridging had more bleeding events than those who received modified dose bridging (10.9 vs. 1.4%, p = 0.466). Following implementation of the tool, there was a statistically significant decrease in the number of patients who received bridging without an increase in thromboembolic events. There were numerically higher rates of bleeding in those who received bridging. Additional research is needed to evaluate efficacy and safety of prophylactic versus treatment dose bridging and how implementation of peri-procedural antithrombotic tools reflecting the emerging evidence will affect patient outcomes, satisfaction and healthcare costs.

Extended thromboprophylaxis in the acutely ill medical patient after hospitalization - a paradigm shift in post-discharge thromboprophylaxis.

Venous thromboembolism (VTE) is a significant healthcare burden with approximately 900,000 events annually in the United States, over half of which are healthcare-associated. This number is anticipated to double by 2050. Group prophylaxis strategies confined to the inpatient setting appear to have minimal impact on the reduction of post-discharge VTE in medically ill patients due to shortened lengths of stay and a heterogenous population that includes patients at low risk for VTE. In accordance with current guideline recommendations, very few (<5%) medically ill patients are discharged with extended prophylaxis, which potentially creates a clinical gap for at-risk patients as VTE risk has been shown to persist for up to 90 days. Initial studies of extended thromboprophylaxis in acutely ill medical patients with enoxaparin, rivaroxaban and apixaban showed little to no benefit towards VTE reduction that was consistently outweighed by increased bleeding. The more recent APEX study that compared betrixaban to enoxaparin in an enriched patient population at high-risk for VTE was the first study of extended thromboprophylaxis that showed similar efficacy in VTE prevention without an increase in major bleeding. Based on the APEX results, betrixaban recently gained FDA approval for extended thromboprophylaxis in acutely ill medical patients. Recognition that up to half of medically ill patients are not at sufficient risk to warrant thromboprophylaxis has driven extensive research towards development of scientifically derived and validated VTE risk assessment models intended to identify patients who do not warrant prophylaxis, as well as those at high risk who may derive benefit from extended thromboprophylaxis. This article will review prior and ongoing extended thromboprophylaxis studies, VTE and bleed risk assessment models, incorporation of biomarkers in VTE risk assessment and key issues in the paradigm shift towards individualized VTE prophylaxis in acutely ill medical patients.

Optimizing diagnostic testing for venous thromboembolism.

Diagnostic algorithms for venous thromboembolism exist, but most do not provide detailed guidance as to which patients, if any, may benefit from screening for thrombophilia. This article provides an overview of the optimized diagnosis of venous thromboembolism, with a focus on the appropriate use of thrombophilia screening.

Renal Function and Direct Oral Anticoagulant Treatment for Venous Thromboembolism.

Because differences in renal function can affect the efficacy and safety of direct oral anticoagulants, prescribing an appropriate dose based on renal function is critical, especially in patient populations with a high incidence of renal impairment. In patients with nonvalvular atrial fibrillation and mild or moderate renal impairment, direct oral anticoagulants are associated with a better risk-benefit profile compared with warfarin. However, less is known regarding outcomes in patients with venous thromboembolism and renal impairment. The efficacy and safety of direct oral anticoagulants in patients with venous thromboembolism and renal impairment are primarily derived from prespecified subgroup analyses of the phase 3 clinical trials. We summarize the available data on direct oral anticoagulant use in patients with venous thromboembolism and renal impairment. Clinicians are encouraged to follow study inclusion/exclusion criteria and perform renal dose adjustments based on the Cockcroft-Gault equation using actual body weight when indicated to avoid adverse events.

Renal Function Considerations for Stroke Prevention in Atrial Fibrillation.

Renal impairment increases risk of stroke and systemic embolic events and bleeding in patients with atrial fibrillation. Direct oral anticoagulants (DOACs) have varied dependence on renal elimination, magnifying the importance of appropriate patient selection, dosing, and periodic kidney function monitoring. In randomized controlled trials of nonvalvular atrial fibrillation, DOACs were at least as effective and associated with less bleeding compared with warfarin. Each direct oral anticoagulant was associated with reduced risk of stroke and systemic embolic events and major bleeding compared with warfarin in nonvalvular atrial fibrillation patients with mild or moderate renal impairment. Renal function decrease appears less impacted by DOACs, which are associated with a better risk-benefit profile than warfarin in patients with decreasing renal function over time. Limited data address the risk-benefit profile of DOACs in patients with severe impairment or on dialysis.

Heparin-induced thrombocytopenia: reducing misdiagnosis via collaboration between an inpatient anticoagulation pharmacy service and hospital reference laboratory.

Misdiagnosis of heparin-induced thrombocytopenia (HIT) is common and exposes patients to high-risk therapies and potentially serious adverse events. The primary objective of this study was to evaluate the impact of collaboration between an inpatient pharmacy-driven anticoagulation management service (AMS) and hospital reference laboratory to reduce inappropriate HIT antibody testing via pharmacist intervention and use of the 4T pre-test probability score. Secondary objectives included clinical outcomes and cost-savings realized through reduced laboratory testing and decreased unnecessary treatment of HIT. This was a single center, pre-post, observational study. The hospital reference laboratory contacted the AMS when they received a blood sample for an enzyme-linked immunosorbent HIT antibody (HIT Ab). Trained pharmacists prospectively scored each HIT Ab ordered by using the 4T score with subsequent communication to physicians recommending for or against processing and reporting of lab results. Utilizing retrospective chart review and a database for all patients with a HIT Ab ordered during the study period, we compared the incidence of HIT Ab testing before and after implementation of the pharmacy-driven 4T score intervention. Our intervention significantly reduced the number of inappropriate HIT Ab tests processed (176 vs. 63, p < 0.0001), with no increase in thrombotic or hemorrhagic events. Overall incidence of suspected and confirmed HIT was <3 and <0.005 %, respectively. Overall cost savings were $75,754 (US) or 62 % per patient exposed to heparin between the pre and post intervention groups. Collaboration between inpatient pharmacy AMS and hospital reference laboratories can result in reduction of misdiagnosis of HIT and significant cost savings with similar safety.

Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment.

Venous thromboembolism (VTE) is a serious medical condition associated with significant morbidity and mortality, and an incidence that is expected to double in the next forty years. The advent of direct oral anticoagulants (DOACs) has catalyzed significant changes in the therapeutic landscape of VTE treatment. As such, it is imperative that clinicians become familiar with and appropriately implement new treatment paradigms. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for VTE treatment with the DOACs. When possible, guidance statements are supported by existing published evidence and guidelines. In instances where evidence or guidelines are lacking, guidance statements represent the consensus opinion of all authors of this manuscript and are endorsed by the Board of Directors of the Anticoagulation Forum.The authors of this manuscript first developed a list of pivotal practical questions related to real-world clinical scenarios involving the use of DOACs for VTE treatment. We then performed a PubMed search for topics and key words including, but not limited to, apixaban, antidote, bridging, cancer, care transitions, dabigatran, direct oral anticoagulant, deep vein thrombosis, edoxaban, interactions, measurement, perioperative, pregnancy, pulmonary embolism, reversal, rivaroxaban, switching, \thrombophilia, venous thromboembolism, and warfarin to answer these questions. Non- English publications and publications > 10 years old were excluded. In an effort to provide practical information about the use of DOACs for VTE treatment, answers to each question are provided in the form of guidance statements, with the intent of high utility and applicability for frontline clinicians across a multitude of care settings.

Catheter-directed thrombolysis with alteplase and bivalirudin in a patient with heparin-induced thrombocytopenia.

PURPOSE: The case of a patient with confirmed heparin-induced thrombocytopenia (HIT) and anticoagulation failure undergoing catheter-directed thrombolysis (CDT) with alteplase and bivalirudin for extensive thrombosis is reported. SUMMARY: A 48-year-old, morbidly obese Caucasian woman was admitted to a trauma-surgical intensive care unit (TSICU) after a motor vehicle accident. The patient suffered aortic and renal lacerations, multiple rib and spinal fractures, pleural effusion, bilateral subdural hematomas, and cerebral edema. An inferior vena cava (IVC) filter was placed on hospital day 3, and prophylactic enoxaparin was initiated. The patient was diagnosed with HIT on hospital day 10. Systemic bivalirudin was initiated, and the patient was transitioned to therapeutic fondaparinux on hospital day 13. The patient continued to improve and was transferred from the TSICU to a step-down unit a few days later; the IVC filter remained in place. On hospital day 20, the patient developed respiratory distress and was transferred back to the TSICU. Computed tomography angiography was performed and revealed a questionable pulmonary embolism and distended IVC and iliac veins. Lower-extremity Doppler ultrasound revealed extensive thrombosis. On hospital day 21, the patient underwent CDT with alteplase and bivalirudin infusions through two CDT sheaths for approximately 36 hours, after which most of the thrombus had dissipated. The IVC filter and drug administration sheaths were removed. After the procedure, the patient received bivalirudin and was later transitioned to warfarin. CONCLUSION: A 48-year-old woman with HIT and anticoagulation failure possibly due to the presence of an IVC filter was successfully treated with CDT using alteplase and bivalirudin.

The future of inpatient anticoagulation management.

Anticoagulation therapy management has evolved dramatically in both the outpatient and inpatient arenas over the last 30 years in the interest of optimizing patient safety and outcomes. With the advent of target specific oral anticoagulants and next generation antiplatelet agents, a new world of "antithrombosis management" is quickly becoming evident. Additionally, significant changes to the healthcare system in the United States are anticipated with the implementation of the Healthcare Affordability Act. Collectively, these changes constitute the next major evolution in the management of patients on antithrombotic therapy. This article is intended to serve as a call to action for inpatient anticoagulation management services and specialists to familiarize themselves with potential changes, consider the impact they may have and proactively optimize their structure and services to be better able to embrace and capitalize on change.