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The Western Journal of Emergency... Jan 2015Historically, most patients who required parenteral anticoagulation received heparin, whereas those patients requiring oral anticoagulation received warfarin. Due to the... (Review)
Review
Historically, most patients who required parenteral anticoagulation received heparin, whereas those patients requiring oral anticoagulation received warfarin. Due to the narrow therapeutic index and need for frequent laboratory monitoring associated with warfarin, there has been a desire to develop newer, more effective anticoagulants. Consequently, in recent years many novel anticoagulants have been developed. The emergency physician may institute anticoagulation therapy in the short term (e.g. heparin) for a patient being admitted, or may start a novel anticoagulation for a patient being discharged. Similarly, a patient on a novel anticoagulant may present to the emergency department due to a hemorrhagic complication. Consequently, the emergency physician should be familiar with the newer and older anticoagulants. This review emphasizes the indication, mechanism of action, adverse effects, and potential reversal strategies for various anticoagulants that the emergency physician will likely encounter.
Topics: Anticoagulants; Antithrombins; Embolism; Emergency Service, Hospital; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Thrombosis; Warfarin
PubMed: 25671002
DOI: 10.5811/westjem.2014.12.22933 -
Clinical and Applied... Jul 2017Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability,... (Review)
Review
Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss. Although minor bleed may be managed with discontinuation of anticoagulant, major bleed may require transfusion of blood products and use of specific antidote. The residual effects of each anticoagulant may be monitored with distinct coagulation assay. Intravenous or oral vitamin K can reverse the effect of warfarin within 24 to 48 hours and is indicated for any bleeding, international normalized ratio of >10 or 4.5 to 10 in patients with other risk factors for bleeding. Fresh frozen plasma or prothrombin complex concentrate (PCC) may be necessary in major bleeding related to warfarin. Protamine sulfate reverses the effect of unfractionated heparin completely and of low-molecular-weight heparin (LMWH) partially. Idarucizumab has recently been approved in United States for dabigatran reversal, whereas andexanet alfa is expected to get approved in the near future for reversal of oral factor Xa inhibitors. The PCC may reverse the effect of rivaroxaban to some extent, but no data are available regarding reversal of apixaban and edoxaban. Aripazine has shown promising results to reverse the effects of LMWH, fondaparinux, and direct oral anticoagulants but is still in the developmental phase.
Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Blood Coagulation Factors; Blood Coagulation Tests; Hemorrhage; Humans; International Normalized Ratio; Plasma; Protamines
PubMed: 27789605
DOI: 10.1177/1076029616675970 -
Journal of the American College of... Feb 2017Periprocedural management of anticoagulation is a common clinical conundrum that involves a multidisciplinary team, cuts across many specialties, and varies greatly...
2017 ACC Expert Consensus Decision Pathway for Periprocedural Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation: A Report of the American College of Cardiology Clinical Expert Consensus Document Task Force.
Periprocedural management of anticoagulation is a common clinical conundrum that involves a multidisciplinary team, cuts across many specialties, and varies greatly between institutions in the way it is practiced. Nowhere is this more evident than in the management of patients with nonvalvular atrial fibrillation. Although they have been found to improve patient outcomes, standardized evidence-based protocols are infrequently in place. The frequency of anticoagulant interruption in preparation for a procedure is high, with an estimated 250,000 patients undergoing temporary interruption annually in North America alone. Knowledge about risk of bleeding and short-term thrombotic risk resides in many specialties, further complicating the issue. Our goal in creating this pathway is to help guide clinicians in the complex decision making in this area. In this document, we aim to: 1) validate the appropriateness of the decision to chronically anticoagulate; 2) guide clinicians in the decision of whether to interrupt anticoagulation; 3) provide direction on how to interrupt anticoagulation with specific guidance for vitamin K antagonists and direct-acting oral anticoagulants; 4) evaluate whether to bridge with a parenteral agent periprocedurally; 5) offer advice on how to bridge; and 6) outline the process of restarting anticoagulation post-procedure.
Topics: Anticoagulants; Atrial Fibrillation; Cardiology; Decision Trees; Humans; Perioperative Care; Stroke
PubMed: 28081965
DOI: 10.1016/j.jacc.2016.11.024 -
Annals of Emergency Medicine Oct 2020Bleeding is the most common complication of anticoagulant use. The evaluation and management of the bleeding patient is a core competency of emergency medicine. As the...
Bleeding is the most common complication of anticoagulant use. The evaluation and management of the bleeding patient is a core competency of emergency medicine. As the prevalence of patients receiving anticoagulant agents and variety of anticoagulants with different mechanisms of action, pharmacokinetics, indications, and corresponding reversal agents increase, physicians and other clinicians working in the emergency department require a current and nuanced understanding of how best to assess, treat, and reverse anticoagulated patients. In this project, we convened an expert panel to create a consensus decision tree and framework for assessment of the bleeding patient receiving an anticoagulant, as well as use of anticoagulant reversal or coagulation factor replacement, and to address controversies and gaps relevant to this topic. To support decision tree interpretation, the panel also reached agreement on key definitions of life-threatening bleeding, bleeding at a critical site, and emergency surgery or urgent invasive procedure. To reach consensus recommendations, we used a structured literature review and a modified Delphi technique by an expert panel of academic and community physicians with training in emergency medicine, cardiology, hematology, internal medicine/thrombology, pharmacology, toxicology, transfusion medicine and hemostasis, neurology, and surgery, and by other key stakeholder groups.
Topics: Anticoagulants; Consensus; Drug Antagonism; Emergency Service, Hospital; Expert Testimony; Hemorrhage; Humans
PubMed: 31732375
DOI: 10.1016/j.annemergmed.2019.09.001 -
Journal of Thrombosis and Thrombolysis Jan 2016Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the... (Review)
Review
Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.
Topics: Anticoagulants; Heparin; Humans; Practice Guidelines as Topic; Venous Thromboembolism
PubMed: 26780745
DOI: 10.1007/s11239-015-1315-2 -
The American Journal of Emergency... Sep 2020Anticoagulation is key to the treatment/prevention of thromboembolic events. The primary complication of anticoagulation is serious or life-threatening hemorrhage, which... (Review)
Review
Anticoagulation is key to the treatment/prevention of thromboembolic events. The primary complication of anticoagulation is serious or life-threatening hemorrhage, which may necessitate prompt anticoagulation reversal; this could also be required for nonbleeding patients requiring urgent/emergent invasive procedures. The decision to reverse anticoagulation should weigh the benefit-risk ratio of supporting hemostasis versus post-reversal thrombosis. We appraise the available guidelines/recommendations for vitamin K antagonist (VKA) and direct oral anticoagulant (DOAC) reversal in the management of major bleeding, and also assess recent clinical data that may not yet be reflected in official guidance. In general, available guidelines are consistent in their recommendations, advocating administration of vitamin K and 4-factor prothrombin complex concentrates (4F-PCCs) rather than fresh frozen plasma to patients with VKA-associated intracranial hemorrhage and life-threatening bleeding, and specific reversal agents as essential therapy for DOAC reversal in those same severe conditions. However, guidelines also recommend off-label use of PCCs for DOAC reversal when specific reversal agents are unavailable. Limited recent evidence generally support the latter recommendation, but guidelines are likely to evolve as more data become available.
Topics: Anticoagulants; Consensus; Hemorrhage; Humans; Practice Guidelines as Topic; Vitamin K
PubMed: 32750627
DOI: 10.1016/j.ajem.2020.05.086 -
Journal of Thrombosis and Thrombolysis Jan 2016Venous thromboembolism (VTE) is a serious medical condition associated with significant morbidity and mortality, and an incidence that is expected to double in the next... (Review)
Review
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.
Topics: Administration, Oral; Anticoagulants; Female; Humans; Male; Practice Guidelines as Topic; Pregnancy; Venous Thromboembolism
PubMed: 26780747
DOI: 10.1007/s11239-015-1310-7 -
Marine Drugs Oct 2020Thrombosis remains a prime reason of mortality worldwide. With the available antithrombotic drugs, bleeding remains the major downside of current treatments. This raises... (Review)
Review
Thrombosis remains a prime reason of mortality worldwide. With the available antithrombotic drugs, bleeding remains the major downside of current treatments. This raises a clinical concern for all patients undergoing antithrombotic therapy. Novel antithrombotics from marine sources offer a promising therapeutic alternative to this pathology. However, for any potential new molecule to be introduced as a real alternative to existing drugs, the exhibition of comparable anticoagulant potential with minimal off-target effects must be achieved. The relevance of marine antithrombotics, particularly sulfated polysaccharides, is largely due to their unique mechanisms of action and lack of bleeding. There have been many investigations in the field and, in recent years, results have confirmed the role of potential marine molecules as alternative antithrombotics. Nonetheless, further clinical studies are required. This review covers the core of the data available so far regarding the science of marine molecules with potential medical applications to treat thrombosis. After a general discussion about the major biochemical steps involved in this pathology, we discuss the key structural and biomedical aspects of marine molecules of both low and high molecular weight endowed with antithrombotic/anticoagulant properties.
Topics: Animals; Anticoagulants; Aquatic Organisms; Fibrinolytic Agents; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Polysaccharides; Thrombosis
PubMed: 33066214
DOI: 10.3390/md18100514 -
Small (Weinheim An Der Bergstrasse,... Nov 2022Despite nearly a century of clinical use as a blood thinner, heparin's rapid serum clearance and potential to induce severe bleeding events continue to urge the...
Despite nearly a century of clinical use as a blood thinner, heparin's rapid serum clearance and potential to induce severe bleeding events continue to urge the development of more effective controlled delivery strategies. Subcutaneous depots that steadily release the anticoagulant into circulation represent a promising approach to reducing overdose frequency, sustaining therapeutic concentrations of heparin in plasma, and prolonging anticoagulant activity in a safe and effective manner. Subcutaneously deliverable heparin-peptide nanogranules that allow for long-lasting heparin bioavailability in the circulatory system, while enabling on-demand activation of heparin's anticoagulant effects in the thrombus microenvironment, are reported. Biophysical studies demonstrate this responsive behavior is due to the sequestration of heparin within self-assembling peptide nanofibrils and its mechanically actuated decoupling to elicit antithrombotic effects at the clotting site. In vivo studies show these unique properties converge to allow subcutaneous nanogranule depots to extend heparin serum concentrations for an order of magnitude longer than standard dosing regimens while enabling prolonged and controlled anticoagulant activity. This biohybrid delivery system demonstrates a potentially scalable platform for the development of safer, easier to administer, and more effective antithrombotic nanotechnologies.
Topics: Humans; Heparin; Fibrinolytic Agents; Thrombosis; Anticoagulants; Peptides
PubMed: 36192159
DOI: 10.1002/smll.202203751 -
BMJ Open Dec 2019Clinical guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) for stroke prevention in most patients with atrial...
Safety of switching from vitamin K antagonist to non-vitamin K antagonist oral anticoagulant in frail elderly with atrial fibrillation: rationale and design of the FRAIL-AF randomised controlled trial.
INTRODUCTION
Clinical guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) for stroke prevention in most patients with atrial fibrillation (AF). Frail elderly were under-represented in the landmark NOAC-trials, leaving a knowledge gap on the optimal anticoagulant management (VKA or NOAC) in this increasing population. The aim of the Frail-AF (FRAIL-AF) study is to assess whether switching from international normalised ratio (INR)-guided VKA-management to a NOAC-based treatment strategy compared with continuing VKA-management is safe in frail elderly patients with AF.
METHODS AND ANALYSIS
The FRAIL-AF study is a pragmatic, multicentre, open-label, randomised controlled clinical trial. Frail elderly (age ≥75 years plus a Groningen Frailty Indicator score ≥3) who receive VKA-treatment for AF in the absence of a mechanical heart valve or severe mitral valve stenosis will be randomised to switch to a NOAC-based treatment strategy or to continue INR-guided VKA-management. Patients with severe renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m) will be excluded from randomisation. Based on existing trial evidence in non-frail patients, we will aim to explore whether NOAC-treatment is superior to VKA-therapy in reducing major or clinically relevant non-major bleeding events. Secondary outcomes include minor bleeding, the composite of ischaemic and haemorrhagic stroke, health-related quality of life and cost-effectiveness. The follow-up period for all subjects is 12 months.
ETHICS AND DISSEMINATION
The protocol was approved by the Medical Research Ethics Committee of the University Medical Center Utrecht, the Netherlands and by the Central Committee on Research Involving Human Subjects, the Netherlands. All patients are asked written informed consent. Results are expected in 2022 and will be disseminated through peer-reviewed journals as well as presentations at national and international conferences.
TRIAL REGISTRATION NUMBER
EudraCT: 2017-000393-11; The Netherlands Trial Registry: 6721 (FRAIL-AF study).
Topics: Aged; Female; Humans; Male; Middle Aged; Administration, Oral; Anticoagulants; Atrial Fibrillation; Frail Elderly; Pragmatic Clinical Trials as Topic; Stroke; Vitamin K; Multicenter Studies as Topic
PubMed: 31888928
DOI: 10.1136/bmjopen-2019-032488