A Practical Review of the Emerging Direct Anticoagulants, Laboratory Monitoring, and Reversal Agents

Millions of patients in the United States use anticoagulation for a variety of indications, such as the prevention of stroke in those with atrial fibrillation (AF) and the treatment and prevention of venous thrombosis. For over six decades warfarin was the only available oral anticoagulant, but now several DOACs are available and their use has become more prevalent in recent years. In spite of this increased use, many physicians remain reluctant to prescribe DOACs due to concerns about bleeding and reversibility.

• Publication year

  2018

• Venue

  Journal of Clinical Medicine

• Publication date

  2018-02-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.3390/jcm7020029PMID 29439477PMCID 5852445
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Argatroban

  2018cited by this paper
• Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial.

  2018cited by this paper
• Idarucizumab for Dabigatran Reversal — Full Cohort Analysis

  2017cited by this paper
• Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study.

  2017cited by this paper
• Ciraparantag safely and completely reverses the anticoagulant effects of low molecular weight heparin.

  2016cited by this paper
• Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

  2016cited by this paper
• Ciraparantag. Heparin neutralizer, Anticoagulant reversal agent

  2016cited by this paper
• Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients.

  2016cited by this paper
• Ciraparantag for enoxaparin reversal: Adding to the evidence.

  2016cited by this paper
• Clinicians’ attitudes and perceptions regarding stroke prevention in atrial fibrillation

  2016cited by this paper
• Prescribing Information

  2015cited by this paper
• Idarucizumab for Dabigatran Reversal.

  2015cited by this paper
• Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity.

  2015cited by this paper
• Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial.

  2015cited by this paper
• A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran

  2015cited by this paper
• Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab

  2015cited by this paper
• Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated With Dabigatran or Warfarin for Nonvalvular Atrial Fibrillation

  2015cited by this paper
• National Trends in Ambulatory Oral Anticoagulant Use.

  2015cited by this paper
• PER977 REVERSES LOW MOLECULAR WEIGHT HEPARIN IN ADDITION TO IIA AND XA NEW ORAL ANTICOAGULANTS

  2015cited by this paper
• Relative Bioavailability of Apixaban Solution or Crushed Tablet Formulations Administered by Mouth or Nasogastric Tube in Healthy Subjects.

  2015cited by this paper
• Use of PER977 to reverse the anticoagulant effect of edoxaban.

  2014cited by this paper
• Rivaroxaban vs. warfarin in Japanese patients with non-valvular atrial fibrillation in relation to age.

  2014cited by this paper
• Abstract 18403: Effect of Dabigatran on the Ability to Generate Fibrin at a Wound site and its Reversal by Idarucizumab, the Antidote to Dabigatran, in Healthy Volunteers: An Exploratory Marker of Blood Loss

  2014cited by this paper
• Idarucizumab Fully Restores Dabigatran-Induced Alterations on Platelet and Fibrin Deposition on Damaged Vessels: Studies in Vitro with Circulating Human Blood

  2014cited by this paper
• Performance of coagulation tests in patients on therapeutic doses of rivaroxaban

  2014cited by this paper
• Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitro.

  2014cited by this paper
• Activated prothrombin complex concentrate for dabigatran‐associated bleeding

  2014cited by this paper
• Determination of dabigatran, rivaroxaban and apixaban by ultra‐performance liquid chromatography – tandem mass spectrometry (UPLC‐MS/MS) and coagulation assays for therapy monitoring of novel direct oral anticoagulants

  2014cited by this paper
• Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants.

  2014cited by this paper
• Clinical toxicology. Preface.

  2014cited by this paper
• Abstract 19361: Reversal of Anticoagulant-induced Bleeding in External and Internal Bleeding Models by PER977, a Small Molecule Anticoagulant Antidote

  2014cited by this paper
• Comparison of three‐factor and four‐factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers

  2014cited by this paper
• Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays

  2013cited by this paper
• Rivaroxaban for thromboprophylaxis in acutely ill medical patients.

  2013cited by this paper
• European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation.

  2013cited by this paper
• Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism.

  2013cited by this paper
• Rivaroxaban for thromboprophylaxis in acutely ill medical patients.

  2013cited by this paper
• Edoxaban versus warfarin in patients with atrial fibrillation.

  2013cited by this paper
• Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (Explore-Xa)

  2013cited by this paper
• Oral apixaban for the treatment of acute venous thromboembolism.

  2013cited by this paper
• [Oral Rivaroxaban for the treatment of symptomatic pulmonary embolism].

  2013cited by this paper
• Apixaban for extended treatment of venous thromboembolism.

  2013cited by this paper
• Measuring oral direct inhibitors of thrombin and factor Xa: a recommendation from the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis

  2013cited by this paper
• Extended use of dabigatran, warfarin, or placebo in venous thromboembolism.

  2013cited by this paper
• Activated prothrombin complex concentrate (APCC)‐mediated activation of factor (F)VIII in mixtures of FVIII and APCC enhances hemostatic effectiveness

  2013cited by this paper
• National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011

  2012cited by this paper
• Argatroban

  2012cited by this paper
• Efficacy and safety of thromboprophylaxis with low-molecular-weight heparin or rivaroxaban in hip and knee replacement surgery

  2012cited by this paper
• Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: Resolving uncertainties in routine practice

  2012cited by this paper
• Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model

  2012influential reference
• Executive Summary Antithrombotic Therapy and Prevention of Thrombosis , 9 th ed : American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

  2012cited by this paper
• Clinical Toxicology

  2012cited by this paper
• Rivaroxaban in patients with a recent acute coronary syndrome.

  2012influential reference
• Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF.

  2012cited by this paper
• Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

  2012cited by this paper
• Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban

  2012cited by this paper
• Development and clinical applications of novel oral anticoagulants. Part II. Drugs under clinical investigation.

  2012cited by this paper
• Apixaban versus Warfarin in Patients with Atrial Fibrillation

  2012cited by this paper
• Oral rivaroxaban for the treatment of symptomatic pulmonary embolism.

  2012cited by this paper
• Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran

  2012cited by this paper
• Effects on routine coagulation screens and assessment of anticoagulant intensity in patients taking oral dabigatran or rivaroxaban: Guidance from the British Committee for Standards in Haematology

  2012cited by this paper
• Apixaban in patients with atrial fibrillation.

  2011cited by this paper
• Hemostatic Therapy in Experimental Intracerebral Hemorrhage Associated With the Direct Thrombin Inhibitor Dabigatran

  2011cited by this paper
• Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment.

  2011cited by this paper
• Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate: A Randomized, Placebo-Controlled, Crossover Study in Healthy Subjects

  2011cited by this paper
• Apixaban versus warfarin in patients with atrial fibrillation.

  2011cited by this paper
• Rivaroxaban versus warfarin in nonvalvular atrial fibrillation

  2011cited by this paper
• Drug and dietary interactions of warfarin and novel oral anticoagulants: an update

  2011cited by this paper
• Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

  2011cited by this paper
• Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity

  2010cited by this paper
• Clinical laboratory measurement of direct factor Xa inhibitors: Anti-Xa assay is preferable to prothrombin time assay

  2010cited by this paper
• Recombinant activated factor VII in controlling bleeding in non-hemophiliac patients

  2010cited by this paper
• Apixaban versus enoxaparin for thromboprophylaxis after hip replacement.

  2010cited by this paper
• Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial.

  2010cited by this paper
• Randomised, parallel-group, multicentre, multinational phase 2 study comparing edoxaban, an oral factor Xa inhibitor, with warfarin for stroke prevention in patients with atrial fibrillation

  2010cited by this paper
• Improve the results of phase II trials of thromboprophylaxis with the new oral anticoagulant drugs

  2010cited by this paper
• Assessment of laboratory assays to measure rivaroxaban – an oral, direct factor Xa inhibitor

  2010cited by this paper
• Prothrombin complex concentrate reverses the anticoagulant effect of rivaroxaban in healthy volunteers

  2010influential reference
• Does timing of surgery matter in fragility hip fractures?

  2010cited by this paper
• Apixaban or enoxaparin for thromboprophylaxis after knee replacement.

  2009cited by this paper
• HIGHLIGHTS OF PRESCRIBING INFORMATION

  2009cited by this paper
• Dabigatran versus warfarin in patients with atrial fibrillation.

  2009cited by this paper
• Dabigatran versus warfarin in the treatment of acute venous thromboembolism.

  2009cited by this paper
• Length of stay, mortality, morbidity and delay to surgery in hip fractures.

  2009cited by this paper
• Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery.

  2009cited by this paper
• Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty.

  2008cited by this paper
• A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT)

  2008cited by this paper
• Bivalirudin during primary PCI in acute myocardial infarction.

  2008cited by this paper
• Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty.

  2008cited by this paper
• The story of the discovery of heparin and warfarin

  2008cited by this paper
• Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial.

  2008cited by this paper
• Recombinant activated factor VII effectively reverses the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin ex vivo as measured using thromboelastography

  2007influential reference
• Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial.

  2007cited by this paper
• Does delay in surgery after hip fracture lead to worse outcomes? A multicenter survey.

  2007influential reference
• Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation

  2007cited by this paper
• Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial.

  2007cited by this paper
• Evaluation of Treatment with Direct Thrombin Inhibitors in Patients with Heparin‐Induced Thrombocytopenia

  2006influential reference
• Warfarin: almost 60 years old and still causing problems.

  2006cited by this paper
• Clinical use of plasma and plasma fractions.

  2006cited by this paper
• Bivalirudin for patients with acute coronary syndromes.

  2006cited by this paper

• Apixaban anti‐Xa levels in clinical practice: A case report

  2024cites this paper
• Efficacy and safety of direct oral anticoagulants versus warfarin in the treatment of cerebral venous sinus thrombosis

  2024cites this paper
• Updates on the non-vitamin K oral anti-coagulants (NOACs)

  2024cites this paper
• A Functional RNA-Origami as Direct Thrombin Inhibitor with Fast-acting and Specific Single-Molecule Reversal Agents in vivo model.

  2024cites this paper
• Inhibitory potential of recombinant and native peanut Bowman-Birk inhibitor against proteases of human blood coagulation pathway

  2024cites this paper
• The effect of anticoagulation therapy on the surgical outcomes of minimally invasive major gastrointestinal surgery

  2024cites this paper
• A comparison of front-line oral anticoagulants for the treatment of non-valvular atrial fibrillation: effectiveness and safety of direct oral anticoagulants in the FANTASIIA registry

  2022cites this paper
• Dabigatran: Clinical correlation of drug and its dose with risk of stroke and bleeding

  2022cites this paper
• Portal vein thrombosis: A concise review (Review).

  2021cites this paper
• Minimally invasive acute care surgery.

  2021cites this paper
• Engineering a "three-in-one" hirudin prodrug to reduce bleeding risk: A proof-of-concept study.

  2021cites this paper
• Oral Anticoagulants in Atrial Fibrillation Patients With Recent Stroke Who Are Dependent on the Daily Help of Others

  2021cites this paper
• Identification of the functional food ingredients with antithrombotic properties via virtual screen and experimental studies.

  2021cites this paper
• Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin.

  2021cites this paper
• Direct Oral Anticoagulants: From Randomized Clinical Trials to Real-World Clinical Practice

  2021cites this paper
• In Brief.

  2021cites this paper
• Direct oral anticoagulants (DOACs) and neck of femur fractures: Standardising the perioperative management and time to surgery.

  2020cites this paper
• Comparison of Traumatic Intracranial Hemorrhage Expansion and Outcomes Among Patients on Direct Oral Anticoagulants Versus Vitamin k Antagonists

  2020cites this paper
• Therapeutic strategies for thrombosis: new targets and approaches

  2020cites this paper
• Chronic Kidney Disease and Its Impact on a Prothrombotic State in Patients with Atrial Fibrillation

  2020cites this paper
• Intravenous Immunoglobulin (IVIG) in Severe Heparin-Induced Thrombocytopenia (HIT) in a Traumatic Brain Injury (TBI) Patient with Cerebral Venous Sinus Thrombosis (CVST)

  2020cites this paper
• Retrospective Review on the Safety and Efficacy of Direct Oral Anticoagulants Compared With Warfarin in Patients With Cirrhosis.

  2020cites this paper
• Portal vein thrombosis in the practice of the internist

  2020cites this paper
• Oral Anticoagulants in Cardiovascular Surgery: Between Nightmare Tour and Safe Cruise.

  2019cites this paper
• Emergency Visits for Oral Anticoagulant Bleeding

  2019cites this paper
• Oral Anticoagulant Therapy—When Art Meets Science

  2019cites this paper
• Non-medical prescribing: a reflective case study on prescribing anticoagulation for deep vein thrombosis.

  2019cites this paper
• Update on Management of Portal Vein Thrombosis and the Role of Novel Anticoagulants

  2019cites this paper
• Assessment of ICD‐10‐CM code assignment validity for case finding of outpatient anticoagulant‐related bleeding among Medicare beneficiaries

  2019cites this paper
• Natural constituents of St. John's Wort inhibit the proteolytic activity of human thrombin.

  2019cites this paper
• The acceptability of a direct oral anticoagulant monitoring regimen among patients with atrial fibrillation: a pilot study

  2019cites this paper
• Rapidly Neutralizable and Highly Anticoagulant Thrombin-Binding DNA Aptamer Discovered by MACE SELEX

  2019cites this paper
• Computer Design of Low-Molecular-Weight Inhibitors of Coagulation Factors

  2019cites this paper
• The New/Novel Oral Anticoagulants and Their Impact on Patients Being Considered for Shockwave Lithotripsy: The Findings of an International Survey of the Endourological Society

  2019cites this paper
• New anticoagulants, reversal agents, and clinical considerations for perioperative practice.

  2018cites this paper
• Anticoagulation Across Care Transitions: Identifying Minimum Data to Maximize Drug Safety.

  2018cites this paper