Allison Burnett

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.

Pharmacology of anticoagulants used in the treatment of venous thromboembolism

Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE.

Delivery of Optimized Inpatient Anticoagulation Therapy: Consensus Statement from the Anticoagulation Forum

OBJECTIVE To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients; the guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. DATA SOURCES The medical literature was reviewed using MEDLINE (1946-January 2013), EMBASE (1980-January 2013), and PubMed (1947-January 2013) for topics and key words including, but not limited to, standards of practice, national guidelines, patient safety initiatives, and regulatory requirements pertaining to anticoagulant use in the inpatient setting. Non-English-language publications were excluded. Specific MeSH terms used include algorithms, anticoagulants/administration and dosage/adverse effects/therapeutic use, clinical protocols/standards, decision support systems, drug monitoring/methods, humans, inpatients, efficiency/organizational, outcome and process assessment (health care), patient care team/organization and administration, program development/standards, quality improvement/organization and administration, thrombosis/drug therapy, thrombosis/prevention and control, risk assessment/standards, patient safety/standards, and risk management/methods. STUDY SELECTION AND DATA EXTRACTION Because of this documents scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors and are endorsed by the Board of Directors of the Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of patients receiving anticoagulation therapy. DATA SYNTHESIS Recommendations for delivering optimized inpatient anticoagulation therapy were developed collaboratively by the authors and are summarized in 8 key areas: (1) process, (2) accountability, (3) integration, (4) standards of practice, (5) provider education and competency, (6) patient education, (7) care transitions, and (8) outcomes. Recommendations are intended to inform the development of coordinated care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized inpatient anticoagulation therapy are intended to apply to all clinicians involved in the care of hospitalized patients receiving anticoagulation therapy. CONCLUSIONS Anticoagulants are high-risk medications associated with a significant rate of medication errors among hospitalized patients. Several national organizations have introduced initiatives to reduce the likelihood of patient harm associated with the use of anticoagulants. Health care organizations are under increasing pressure to develop systems to ensure the safe and effective use of anticoagulants in the inpatient setting. This document provides consensus guidelines for anticoagulant therapy in the inpatient setting and serves as a companion document to prior guidelines relevant for outpatients.

Care Transitions Service: A pharmacy-driven program for medication reconciliation through the continuum of care

PURPOSE A quality-improvement program at University of New Mexico Hospital (UNMH) encompassing admission, discharge, and postdischarge medication reconciliation activities is described, with a report on initial assessments of the programs impact on rates of medication-related problems (MRPs). METHODS Pharmacists conducted a five-month evaluation of the UNMH Care Transitions Service (CTS), which serves inpatients admitted to the hospitals family medicine service, providing medication reconciliation and targeted MRP interventions. Selected patients who received CTS services from November 2012 through March 2013 (n = 191) were included in the analysis. The study endpoints were the rates and types of MRPs identified, the most commonly implicated medication classes, and predictors of MRPs. Postdischarge MRP rates during a two-month trial of CTS services at a UNMH outpatient clinic were also evaluated. RESULTS During the five-month evaluation of inpatient CTS services, a total of 1140 MRPs were identified (an average of 6 per patient), about 70% of which were resolved independently of provider review using pharmacy-driven protocols. During the two-month pilot test of CTS outpatient services (n = 16), a total of 28 MRPs were identified; in over 80% of cases, there was a decline in the number of MRPs from the admission to the postdischarge medication reconciliation. CONCLUSION MRPs were identified through the continuum of care. The majority of MRPs identified in both the inpatient and outpatient settings involved patient variables and patient nonadherence. Seventy percent of inpatient MRPs were resolved independently by the CTS team under pharmacy-driven protocols.

Effect of fondaparinux prophylaxis on anti-factor Xa concentrations in patients with morbid obesity

PURPOSE Anti-factor Xa values in morbidly obese patients receiving standard doses of fondaparinux sodium for the prevention of venous thromboembolism (VTE) were analyzed in a retrospective chart evaluation. SUMMARY The administration of low-molecular-weight heparins to obese patients (body mass index [BMI] of ≥30 kg/m(2)) at the dose recommended for VTE prophylaxis has been reported to result in increased thromboembolic events and decreased anti-factor Xa levels, and some evidence indicates that weight-based dosing adjustments may be appropriate. To study this phenomenon among morbidly obese patients (BMI of ≥40 kg/m(2)), a review of the charts of 45 adult patients for whom steady-state anti-factor Xa laboratory values were obtained after at least four fondaparinux injections was conducted; in all instances, fondaparinux sodium was given at the standard dose (2.5 mg once daily). Of the total of 47 anti-factor Xa values analyzed, 22 (47%) were below the study institutions target peak range (0.3-0.5 mg/L), 20 values (43%) were within the range, and 5 (11%) were above the range. No documented thromboembolic events occurred during hospitalization in the cases evaluated. A stepwise linear regression analysis of selected demographic and clinical variables indicated that better renal function, male sex, increased BMI, and fewer fondaparinux doses were associated with a greater likelihood of diminished anti-factor Xa activity in the cases evaluated. CONCLUSION Anti-factor Xa concentrations in morbidly obese patients receiving fondaparinux sodium 2.5 mg subcutaneously daily for VTE prophylaxis were within or above the target range in 53% of the instances evaluated.

Erratum to: Pharmacology of anticoagulants used in the treatment of venous thromboembolism

Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE.

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.

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.

Comment on: Editorial by Husted et al. “Non-vitamin K antagonist oral anticoagulants (NOACs): No longer new or novel”: (Thromb Haemost 2014; 111: 781–782)

Comment on: Editorial by Husted et al. “Non-vitamin K antagonist oral anticoagulants (NOACs): No longer new or novel” - (Thromb Haemost 2014; 111: 781–782)

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.