Comparison of Managing Factor Xa Inhibitor to Unfractionated Heparin Transitions by aPTT Versus a Treatment Guideline Utilizing Heparin Anti-Xa Levels.

Background: There are inadequate data on the optimal strategy for transitioning factor Xa inhibitors (FXai; apixaban, rivaroxaban) to unfractionated heparin (UFH) infusions.

Objective: In patients transitioning from an FXai to an UFH infusion, this study compared the safety and efficacy of monitoring UFH infusions using an activated partial thromboplastin time (aPTT) titration scale versus utilizing an UFH-calibrated anti-Xa titration scale aided by a novel institutional guideline.

Methods: A retrospective cohort analysis was conducted on adult patients transitioning from an FXai to an UFH infusion at 2 medical centers from June 1, 2018, to November 1, 2020.

Transitioning hospitalized patients from rivaroxaban or apixaban to a continuous unfractionated heparin infusion: A retrospective review.

Purpose: To determine a patient's clinical course based on the use of an activated partial thromboplastin time (aPTT) or heparin anti-Xa assay when transitioning from rivaroxaban or apixaban to an unfractionated heparin infusion.

Methods: A retrospective chart review was conducted to investigate how unfractionated heparin infusions were managed at a tertiary care hospital in the setting of recent apixaban or rivaroxaban administration. Patients were separated into 2 cohorts based on the chosen heparin infusion monitoring assay: heparin anti-Xa or aPTT.

Use of Direct Oral Anticoagulants in Morbidly Obese Patients.

In 2016, the International Society on Thrombosis and Haemostasis (ISTH) published guidelines advising caution when using direct oral anticoagulants (DOACs) in patients with morbid obesity due to limited clinical efficacy and safety data supporting their use in this patient population. In this review, we analyzed published articles in the MEDLINE database (from inception through May 29, 2019), and the Cochrane Library, Google Scholar, and EMBASE databases (from inception through April 26, 2019) that evaluated morbidly obese patients with atrial fibrillation (AF) or venous thromboembolism (VTE) who received DOACs. A total of 19 studies, which included pharmacokinetic studies, original phase III trials for the DOACs, post hoc analyses of phase III trials, and retrospective cohort studies, were evaluated.

Current Strategies for the Management of Bleeding Associated with Direct Oral Anticoagulants and a Review of Investigational Reversal Agents.

Background: The management of life-threatening bleeding in patients who are receiving direct oral anticoagulants (DOACs) is a serious medical concern.

Objective: This review provides a concise, balanced overview of the current and future approaches for reversing the anticoagulation effects of DOACs, particularly factor Xa (FXa) inhibitors.

Discussion: The anticoagulant activity of the direct thrombin inhibitor dabigatran can be reversed by idarucizumab, but until recently, options for the management of major bleeding in patients who were receiving FXa inhibitors were limited to nonspecific strategies, including supplementation of clotting factors with prothrombin complex concentrates (PCCs) or activated PCCs for attenuating anticoagulation effects.

Use of specific anti-Xa levels in acute kidney injury to transition patients from oral factor Xa inhibitors to i.v. heparin infusion.

Purpose: This case series presents 3 patients with acute kidney injury taking apixaban or rivaroxaban and transitioning to a heparin infusion.

Summary: Case 1 was a 78-year-old man admitted with respiratory failure, acute decompensated heart failure, and acute kidney injury. He was taking apixaban for atrial flutter.

Successful use of laboratory monitoring to facilitate an invasive procedure for a patient treated with dabigatran.

Purpose: A case in which novel and traditional laboratory markers were successfully used to determine surgical intervention timing in an elderly patient receiving dabigatran for atrial fibrillation is reported.

Summary: An 86-year-old woman who was taking dabigatran for atrial fibrillation suffered a right femoral neck fracture requiring surgical intervention. Dabigatran was withheld once the patient was admitted to the hospital, and the pharmacy inpatient anticoagulation management team was consulted for guidance on determining appropriate scheduling of surgical intervention with regard to the time since her most recent dabigatran dose to minimize bleeding complications.

Overview of direct oral anticoagulant therapy reversal.

Purpose: Strategies for the management of bleeding complications and facilitation of an invasive procedure in patients receiving direct oral anticoagulants (DOACs) are reviewed.

Summary: The DOACs provide clinical advantages versus vitamin K antagonists, including fixed dosing with no routine coagulation monitoring and evidence of a lower risk of bleeding. However, as with all anticoagulants, there is a risk of bleeding complications in patients receiving DOACs, so urgent reversal of their anticoagulant activity may be required for spontaneous or traumatic bleeding events and in patients undergoing emergency invasive procedures.

Relationship between time spent at extreme International Normalized Ratios and time in therapeutic range with bleeding and thrombosis in warfarin-treated patients.

Purpose: The relationship between the time spent at extreme International Normalized Ratios (INRs) and the time in the therapeutic range (TTR) with bleeding and thrombosis in warfarin-treated patients was examined.

Methods: Consecutive patients treated with warfarin for atrial fibrillation or for venous thrombosis who were managed by the anticoagulation management service or adult internal medicine clinic of a large, tertiary care, integrated health system between June 1, 2011, and October 9, 2012, were eligible for study inclusion. Data collected for the outcomes analysis included INRs and dates; current use of aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, or nonsteroidal antiinflammatory drugs; and any clinically significant bleeding or thrombosis events identified.

Pharmacokinetic and pharmacodynamic drug interactions with new oral anticoagulants: what do they mean for patients with atrial fibrillation?

Objective: To review pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs) involving new oral anticoagulants for atrial fibrillation.

Data Sources: A literature search was conducted via PubMed and the Cochrane database to identify DDI studies using the terms drug interactions, dabigatran, rivaroxaban, and apixaban. Prescribing information and Food and Drug Administration briefing documents were used to supplement published data.

Rivaroxaban: practical considerations for ensuring safety and efficacy.

Rivaroxaban is the first agent available within a new class of anticoagulants called direct factor Xa inhibitors. Rivaroxaban is approved for use in the United States for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the prevention of deep vein thrombosis in patients undergoing total hip replacement and total knee replacement, for the treatment of deep vein thrombosis and pulmonary embolism, and for the reduction in risk of recurrence of deep vein thrombosis and pulmonary embolism (with additional indications under review). Rivaroxaban dose and frequency of administration vary depending on the indication.

One-year adherence to warfarin treatment for venous thromboembolism in high-risk patients and its association with long-term risk of recurrent events.

Backgrounds: Warfarin is the predominant oral anticoagulant used for the prevention of recurrent venous thromboembolism (VTE) events. However, its long-term use is complicated by the need to manage the drug within a narrow therapeutic range and by possible food and drug interactions.

Objective: To examine the association between 1-year adherence, measured through compliance with and persistence on warfarin treatment for VTE, and long-term risk of recurrent events among patients at high risk.

New oral therapies for the prevention and treatment of venous thromboembolism.

Purpose: Data comparing traditional and novel anticoagulants are reviewed, and the potential use of new oral agents for the prevention and treatment of venous thromboembolism (VTE) is assessed.

Summary: Practical challenges in using traditional anticoagulants are well established and have led to the search for new oral agents. Apixaban, rivaroxaban, and dabigatran etexilate are new oral anticoagulants that may offer simpler, more effective, and safer treatment and prevention of VTE, which may increase adherence to such therapy, improve outcomes, and decrease overall health care costs.

High-dose argatroban for treatment of heparin-induced thrombocytopenia with thrombosis: a case report and review of laboratory considerations.

Purpose: A case report describing high-dose argatroban for the treatment of heparin-induced thrombocytopenia (HIT) with thrombosis and associated considerations in interpreting laboratory monitoring data are presented.

Summary: A 51-year-old woman with an extensive history of coronary artery disease arrived at the emergency department with complaints of chest pain. The patient was admitted, and coronary artery bypass graft surgery was ultimately performed.

Inpatient warfarin: experience with a pharmacist-led anticoagulation management service in a tertiary care medical center.

Purpose: The implementation of a pharmacist-led anticoagulation management service (AMS) and the clinical outcomes of inpatients receiving warfarin management are described.

Summary: An AMS was established at St. Mary's Medical Center (SMMC) in Duluth, Minnesota, in November 2003 at the request of orthopedic surgeons to manage warfarin for their patients postoperatively.

Dabigatran etexilate in clinical practice: confronting challenges to improve safety and effectiveness.

A number of novel anticoagulants are moving through various stages of drug development. Recently, the United States Food and Drug Administration approved the oral direct thrombin inhibitor dabigatran etexilate to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Although dabigatran offers a number of advantages over existing oral and parenteral anticoagulants, challenges exist for clinicians who must ensure its safe and effective use.

Key articles and guidelines in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a significant medical diagnosis that affects millions of patients each year. Appropriate management of VTE can help treat the initial event as well as reduce the frequency of complications such as postthrombotic syndrome, pulmonary hypertension, and death. Due to increasing regulatory requirements, hospitals nationwide are developing necessary documentation of appropriate and safe use of anticoagulants for the management of VTE.

Pharmacogenomics of warfarin: uncovering a piece of the warfarin mystery.

Purpose: The literature on the pharmacogenomics of warfarin and the use of genetic testing to optimize initial and maintenance warfarin dosing is reviewed.

Summary: Warfarin tablets contain a racemic mixture of R- and S-isomers. The S-isomer is responsible for about 70% of warfarin's anticoagulant effect.

Rivaroxaban: an oral direct inhibitor of factor Xa.

Purpose: The mechanism of action, pharmacodynamics, pharmacokinetics, efficacy in clinical trials, interactions, adverse effects and toxicity, and place in therapy of rivaroxaban are reviewed.

Summary: Rivaroxaban, the first oral, direct factor Xa (FXa) inhibitor to reach Phase III trials, inhibits thrombin generation by both the intrinsic and the tissue factor pathways. It has shown predictable, reversible inhibition of FXa activity, and it may have the ability to inhibit clot-bound FXa.

Implementing anticoagulation management by pharmacists in the inpatient setting.

Purpose: This article identifies approaches for implementing an inpatient anticoagulation program involving pharmacists; two successful inpatient anticoagulation programs previously reported in the literature are described with a discussion of steps to consider in developing or expanding such a service.

Summary: Two institutions implemented pharmacist-managed anticoagulation services. One institution identified an undesirable incidence of medication-related adverse events occurring in hospitalized patients receiving anticoagulants.

Ximelagatran: an orally active direct thrombin inhibitor.

Purpose: The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, contraindications, and adverse effects of ximelagatran are reviewed.

Summary: Ximelagatran is the first orally active direct thrombin inhibitor to be tested in Phase III clinical trials. After oral administration, ximelagatran is rapidly converted to its active metabolite, melagatran.