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Frontiers in Bioscience (Landmark... Jun 2016Heparin, a sulfated polysaccharide, has been used as a clinical anticoagulant for over 90 years. Newer anticoagulants, introduced for certain specialized applications,... (Review)
Review
Heparin, a sulfated polysaccharide, has been used as a clinical anticoagulant for over 90 years. Newer anticoagulants, introduced for certain specialized applications, have not significantly displaced heparin and newer heparin-based anticoagulants in most medical procedures. This chapter, while reviewing anticoagulation and these newer anticoagulants, focuses on heparin-based anticoagulants, including unfractionated heparin, low molecular weight heparins and ultra-low molecular weight heparins. Heparin's structures and its biological and therapeutic roles are discussed. Particular emphasis is placed on heparin's therapeutic application and its adverse effects. The future prospects are excellent for new heparins and new heparin-based therapeutics with improved properties.
Topics: Anticoagulants; Blood Coagulation; Disseminated Intravascular Coagulation; Extracorporeal Circulation; Heparin; Humans; Venous Thromboembolism
PubMed: 27100512
DOI: 10.2741/4462 -
Seminars in Dialysis Nov 2021The most common anticoagulant options for continuous renal replacement therapy (CRRT) include unfractionated heparin (UFH), regional citrate anticoagulation (RCA), and... (Review)
Review
The most common anticoagulant options for continuous renal replacement therapy (CRRT) include unfractionated heparin (UFH), regional citrate anticoagulation (RCA), and no anticoagulation. Less common anticoagulation options include UFH with protamine reversal, low-molecular weight heparin (LMWH), thrombin antagonists, and platelet inhibiting agents. The choice of anticoagulant for CRRT should be determined by patient characteristics, local expertise, and ease of monitoring. The Kidney Disease Improving Global Outcomes (KDIGO) acute kidney injury guidelines recommend using RCA rather than UFH in patients who do not have contraindications to citrate and are with or without increased risk of bleeding. Monitoring should include evaluation of the anticoagulant effect, circuit life, filter efficacy, and complications.
Topics: Acute Kidney Injury; Anticoagulants; Continuous Renal Replacement Therapy; Heparin; Heparin, Low-Molecular-Weight; Humans; Renal Dialysis; Renal Replacement Therapy
PubMed: 33684244
DOI: 10.1111/sdi.12959 -
Journal of Thrombosis and Haemostasis :... Jul 2023Oral anticoagulants are a mainstay for the prevention and treatment of arterial and venous thrombosis. Direct oral anticoagulants (DOACs) have replaced vitamin K... (Review)
Review
Oral anticoagulants are a mainstay for the prevention and treatment of arterial and venous thrombosis. Direct oral anticoagulants (DOACs) have replaced vitamin K antagonists for many indications. Currently available DOACs include dabigatran, which inhibits thrombin, and apixaban, edoxaban, and rivaroxaban, which inhibit factor (F) Xa. A new class of DOACs is under development. These new DOACs, which include asundexian and milvexian, inhibit FXIa, which is positioned in the intrinsic pathway of coagulation. Anticoagulants that target FXIa have the potential to be safer than the current DOACs because there is emerging evidence that FXI is essential for thrombosis but mostly dispensable for hemostasis. In addition to the oral inhibitors of FXIa, parenteral inhibitors are also under development. These include fesomersen, an antisense oligonucleotide that reduces the hepatic synthesis of FXI; abelacimab, an antibody that binds to FXI and blocks its activation; and osocimab, an FXIa inhibitory antibody. Focusing on these new agents, this article describes the unmet needs in oral anticoagulation therapy, explains why FXI is a promising target for new oral anticoagulants, reviews phase 2 clinical data on new agents, describes ongoing phase 3 trials, and provides a perspective on the opportunities and challenges for FXI inhibitors.
Topics: Humans; Administration, Oral; Anticoagulants; Dabigatran; Factor Xa Inhibitors; Factor XI; Rivaroxaban
PubMed: 37116752
DOI: 10.1016/j.jtha.2023.04.021 -
Blood Reviews Jul 2017The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are... (Review)
Review
The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.g., augmented bleeding risk for concomitant use of NSAIDs), interactions with drugs, foods, herbs, and over-the-counter medications may affect the risk/benefit ratio of VKAs. Direct oral anticoagulants (DOACs) including Factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and thrombin inhibitor (dabigatran) are poised to replace warfarin. Phase-3 studies and real-world evaluations have established that the safety profile of DOACs is superior to those of VKAs. However, some pharmacokinetic and pharmacodynamic interactions are expected. Herein we present a critical review of VKAs and DOACs with focus on their potential for interactions with drugs, foods, herbs and over-the-counter medications.
Topics: Animals; Anticoagulants; Drug Interactions; Food-Drug Interactions; Herbal Medicine; Humans; Plant Extracts; Plants, Medicinal; Vitamin K
PubMed: 28196633
DOI: 10.1016/j.blre.2017.02.001 -
Journal of Thrombosis and Haemostasis :... Apr 2021Anticoagulation is central to the management of thrombotic antiphospholipid syndrome (APS). The standard anticoagulant treatment for thrombotic APS is life-long warfarin... (Review)
Review
Anticoagulation is central to the management of thrombotic antiphospholipid syndrome (APS). The standard anticoagulant treatment for thrombotic APS is life-long warfarin or an alternative vitamin K antagonist. The role of direct oral anticoagulants for thrombotic APS is not established due to the lack of definitive evidence and has recently been addressed in international guidance. Other anticoagulant options include low molecular weight heparin, unfractionated heparin, and fondaparinux. In APS patients, lupus anticoagulant can affect phospholipid-dependent coagulation monitoring tests, so that they may not reflect true anticoagulation intensity. Accurate assessment of anticoagulation intensity is essential, to optimize anticoagulant dosing and facilitate thrombus resolution; minimize the risk of recurrent thrombosis or bleeding; inform assessment of whether recurrent thrombosis is related to breakthrough thrombosis while on therapeutic anticoagulation, subtherapeutic anticoagulation, non-adherence, or spurious results; and guide the management of bleeding. Knowledge of anticoagulant intensity also informs assessment and comparison of anticoagulation regimens in clinical studies. Considerations regarding anticoagulation dosing and/or monitoring of thrombotic APS patients underpin appropriate management in special situations, notably APS-related severe renal impairment, which can occur in APS or APS/systemic lupus erythematosus-related nephropathy or catastrophic APS; and APS-related thrombocytopenia. Anticoagulant dosing and monitoring in thrombotic APS patients also require consideration in anticoagulant-refractory APS and during pregnancy. In this review, we summarize the tests generally used in monitoring anticoagulant therapy, use of the main anticoagulants considered for thrombotic APS, lupus anticoagulant effects on anticoagulation monitoring tests, and strategies for appropriate anticoagulant monitoring in thrombotic APS.
Topics: Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation; Female; Heparin; Humans; Pregnancy; Thrombosis
PubMed: 33325604
DOI: 10.1111/jth.15217 -
The Western Journal of Emergency... Aug 2019Owing to the propensity of anticoagulated patients to bleed, a strategy for reversal of anticoagulation induced by any of the common agents is essential. Many patients... (Review)
Review
Owing to the propensity of anticoagulated patients to bleed, a strategy for reversal of anticoagulation induced by any of the common agents is essential. Many patients are anticoagulated with a variety of agents, including warfarin, low molecular weight heparin, and the direct oral anticoagulants such as factor Xa and factor IIa inhibitors. Patients may also be using antiplatelet agents. Recommendations to reverse bleeding in these patients are constantly evolving with the recent development of specific reversal agents. A working knowledge of hemostasis and the reversal of anticoagulation and antiplatelet drugs is required for every emergency department provider. This article reviews these topics and presents the currently recommended strategies for dealing with bleeding in the anticoagulated patient.
Topics: Anticoagulants; Emergencies; Emergency Service, Hospital; Factor Xa Inhibitors; Hemorrhage; Hemostatic Techniques; Humans; Platelet Aggregation Inhibitors
PubMed: 31539334
DOI: 10.5811/westjem.2018.5.38235 -
Neurosurgery Clinics of North America Oct 2018Anticoagulant medications are used widely for a variety of medical and surgical diseases, disorders, and conditions associated with thrombosis and thromboembolism. This... (Review)
Review
Anticoagulant medications are used widely for a variety of medical and surgical diseases, disorders, and conditions associated with thrombosis and thromboembolism. This review highlights labeled indications, mechanisms of action, potential drug interactions, and specific pharmacokinetic characteristics of available anticoagulants as an essential foundation for guiding selection and management of therapies for patients undergoing neurosurgical procedures.
Topics: Anticoagulants; Biological Availability; Blood Loss, Surgical; Hemostasis, Surgical; Humans; Neurosurgical Procedures
PubMed: 30223963
DOI: 10.1016/j.nec.2018.06.003 -
The American Journal of Medicine May 2017Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract... (Review)
Review
Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery.
Topics: Absorption, Physiological; Administration, Oral; Anticoagulants; Bariatric Surgery; Biological Availability; Drug Monitoring; Energy Intake; Humans; Vitamin K; Warfarin; Weight Loss
PubMed: 28159600
DOI: 10.1016/j.amjmed.2016.12.033 -
Chest Nov 2018The risk of stroke is heterogeneous across different groups of patients with atrial fibrillation (AF), being dependent on the presence of various stroke risk factors. We...
BACKGROUND
The risk of stroke is heterogeneous across different groups of patients with atrial fibrillation (AF), being dependent on the presence of various stroke risk factors. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios.
METHODS
Systematic literature reviews were conducted to identify relevant articles published from the last formal search perfomed for the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). The overall quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted, voted on, and revised until consensus was reached.
RESULTS
For patients with AF without valvular heart disease, including those with paroxysmal AF, who are at low risk of stroke (eg, CHADS-VASc [congestive heart failure, hypertension, age ≥ 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female)] score of 0 in males or 1 in females), we suggest no antithrombotic therapy. The next step is to consider stroke prevention (ie, oral anticoagulation therapy) for patients with 1 or more non-sex CHADS-VASc stroke risk factors. For patients with a single non-sex CHADS-VASc stroke risk factor, we suggest oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel; and for those at high risk of stroke (eg, CHADS-VASc ≥ 2 in males or ≥ 3 in females), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest using a non-vitamin K antagonist oral anticoagulant drug rather than adjusted-dose vitamin K antagonist therapy. With the latter, it is important to aim for good quality anticoagulation control with a time in therapeutic range > 70%. Attention to modifiable bleeding risk factors (eg, uncontrolled BP, labile international normalized ratios, concomitant use of aspirin or nonsteroidal antiinflammatory drugs in an anticoagulated patient, alcohol excess) should be made at each patient contact, and HAS-BLED (hypertension, abnormal renal/liver function [1 point each], stroke, bleeding history or predisposition, labile international normalized ratio, elderly (0.65), drugs/alcohol concomitantly [1 point each]) score used to assess the risk of bleeding where high risk patients (≥ 3) should be reviewed and followed up more frequently.
CONCLUSIONS
Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF with ≥1 non-sex CHADS-VASc stroke risk factor(s).
Topics: Anticoagulants; Atrial Fibrillation; Catheter Ablation; Defibrillators, Implantable; Electric Countershock; Hemorrhage; Humans; Medication Therapy Management; Patient Education as Topic; Risk Assessment; Risk Factors; Stroke
PubMed: 30144419
DOI: 10.1016/j.chest.2018.07.040 -
Emergency Medicine Clinics of North... Aug 2018Today a variety of anticoagulants and antiplatelet agents are available on the market. Given the propensity for bleeding among patients prescribed these medications, the... (Review)
Review
Today a variety of anticoagulants and antiplatelet agents are available on the market. Given the propensity for bleeding among patients prescribed these medications, the emergency medicine physician must be equipped with a working knowledge of hemostasis, and anticoagulant and antiplatelet reversal. This article reviews strategies to address bleeding complications occurring secondary to warfarin, low-molecular-weight heparin, and direct oral anticoagulant therapy.
Topics: Anticoagulants; Hemorrhage; Hemostatic Techniques; Humans; Thromboembolism
PubMed: 30037445
DOI: 10.1016/j.emc.2018.04.014