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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 -
British Journal of Anaesthesia May 2018Neutralisation of systemic anticoagulation with heparin in cardiac surgery with cardiopulmonary bypass requires protamine administration. If adequately dosed, protamine... (Review)
Review
Neutralisation of systemic anticoagulation with heparin in cardiac surgery with cardiopulmonary bypass requires protamine administration. If adequately dosed, protamine neutralises heparin and reduces the risk of postoperative bleeding. However, as its anticoagulant properties are particularly exerted in the absence of heparin, overdosing of protamine may contribute to bleeding and increased transfusion requirements. This narrative review describes the mechanisms underlying the anticoagulant properties and side-effects of protamine, and the impact of protamine dosing on the activated clotting time and point-of-care viscoelastic test results, and explains the distinct protamine dosing strategies in relation to haemostatic activation and postoperative bleeding. The available evidence suggests that protamine dosing should not exceed a protamine-to-heparin ratio of 1:1. In particular, protamine-to-heparin dosing ratios >1 are associated with more postoperative 12 h blood loss. The optimal protamine-to-heparin ratio in cardiac surgery has, however, not yet been elaborated, and may vary between 0.6 and 1.0 based on the initial heparin dose.
Topics: Anticoagulants; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Dose-Response Relationship, Drug; Heparin; Heparin Antagonists; Humans; Postoperative Hemorrhage; Protamines
PubMed: 29661409
DOI: 10.1016/j.bja.2018.01.023 -
Journal of the American Society of... Dec 2018Anticoagulant-related nephropathy (ARN) is a newly recognized form of AKI in which overanticoagulation causes profuse glomerular hemorrhage, which manifests on renal... (Review)
Review
Anticoagulant-related nephropathy (ARN) is a newly recognized form of AKI in which overanticoagulation causes profuse glomerular hemorrhage, which manifests on renal biopsy as numerous renal tubules filled with red cells and red cell casts. The glomeruli show changes, but they are not sufficient to account for the glomerular hemorrhage. We were the first to study ARN, and since then, our work has been confirmed by numerous other investigators. Oral anticoagulants have been in widespread use since the 1950s; today, >2 million patients with atrial fibrillation take an oral anticoagulant. Despite this history of widespread and prolonged exposure to oral anticoagulants, ARN was discovered only recently, suggesting that the condition may be a rare occurrence. This review chronicles the discovery of ARN, its confirmation by others, and our animal model of ARN. We also provide new data on analysis of "renal events" described in the analyses of three pivotal anticoagulation trials and three retrospective analyses of large clinical databases. Taken together, these analyses suggest that ARN is not a rare occurrence in the anticoagulated patient with atrial fibrillation. However, much work needs to be done to understand the condition, particularly prospective studies, to avoid the biases inherent in and retrospective analyses. Finally, we provide recommendations regarding the diagnosis and management of ARN on the basis of the best information available.
Topics: Acute Kidney Injury; Administration, Oral; Animals; Anticoagulants; Creatinine; Disease Models, Animal; Humans; International Normalized Ratio; Kidney; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Risk Factors; Warfarin
PubMed: 30420420
DOI: 10.1681/ASN.2018070741 -
Deutsches Arzteblatt International Nov 2018Much new evidence on oral anticoagulation has come to light in recent years. Non-vitamin-K-dependent oral anti- coagulants (NOAC) have been developed and have been... (Review)
Review
BACKGROUND
Much new evidence on oral anticoagulation has come to light in recent years. Non-vitamin-K-dependent oral anti- coagulants (NOAC) have been developed and have been introduced into clinical practice. In this review, we present the current state of the evidence on anticoagulation for various indications with vitamin K antagonists (VKA) and with NOAC.
METHODS
This review is based on pertinent articles retrieved by a selective search in PubMed (search terms: anticoagulation, atrial fibrillation, prosthetic valve, thrombosis, pulmonary embolism) and on specialty society recommendations and relevant guidelines from the years 2000-2018.
RESULTS
The main indications for oral anticoagulation are atrial fibrillation, venous thromboembolism, and status post heart valve replacement. In patients with atrial fibrillation and without valvular heart disease, anticoagulation is recommended for men with a CHA2DS2-VASc score ≥ 1 and for women with a score ≥ 2. NOAC for this indication are associated with a marginally lower rate of stroke than VKA (3.5% vs. 3.8%, number needed to treat [NNT] = 333) as well as a lower rate of major hemorrhage (5.1% vs. 6.2%, NNT = 91). NOAC are contraindicated for patients with mechanical heart valves. Anticoagulation with VKA can be predictably antagonized. Among the various types of NOAC, the anticoagulant effect of dabigatran can be safely antagonized with an antidote; no specific antidote is yet available for apixaban, rivaroxaban, or edoxaban.
CONCLUSION
The evidence base for anticoagulation over a time frame of several years is inadequate at present, and direct comparative data for the different types of NOAC are not yet available.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Heart Valve Prosthesis; Humans; Risk Assessment; Venous Thromboembolism; Vitamin K
PubMed: 30602410
DOI: 10.3238/arztebl.2018.0776 -
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 -
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 -
Clinical Pharmacokinetics Aug 2020A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of... (Review)
Review
A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of direct oral anticoagulants (DOACs). Concomitant drugs that cause drug-drug interactions (DDIs) alter DOAC exposure by increasing or decreasing DOAC bioavailability and/or clearance; hence, they might affect the efficacy and safety of DOAC therapy. Patients with renal impairment already receive smaller DOAC maintenance doses because avoidance of elevated DOAC exposure might prevent serious bleeding events. For other causes of increased exposure such as DDIs, management is often less well-defined. Considering that DOAC patients are often older and have multiple co-morbidities, polypharmacy is highly prevalent. However, the effect of multiple drugs on DOAC exposure, and especially the impact of DDIs when concurring with drug-disease interactions as observed in renal impairment, has not been thoroughly elucidated. In order to provide effective and safe anticoagulation with DOACs, understanding the mechanisms and magnitude of DDIs appears relevant. Instead of avoiding drug combinations with DOACs, more DDI trials should be conducted and new strategies such as dose adjustments based on therapeutic drug monitoring should be investigated. However, dose adjustments based on concentration measurements cannot currently be recommended because evidence-based data are missing.
Topics: Administration, Oral; Anticoagulants; Drug Interactions; Hemorrhage; Humans; Renal Insufficiency
PubMed: 32157630
DOI: 10.1007/s40262-020-00879-x -
Blood Jan 2020The most important decision in the long-term treatment of venous thromboembolism (VTE) is how long to anticoagulate. VTE provoked by a reversible risk factor, or a first... (Review)
Review
The most important decision in the long-term treatment of venous thromboembolism (VTE) is how long to anticoagulate. VTE provoked by a reversible risk factor, or a first unprovoked isolated distal deep vein thrombosis (DVT), generally should be treated for 3 months. VTE provoked by a persistent or progressive risk factor (eg, cancer), or a second unprovoked proximal DVT or PE, is generally treated indefinitely. First unprovoked proximal DVT or PE may be treated for 3 to 6 months or indefinitely. Male sex, presentation as PE (particularly if concomitant proximal DVT), a positive d-dimer test after stopping anticoagulation, an antiphospholipid antibody, low risk of bleeding, and patient preference favor indefinite anticoagulation. The type of indefinite anticoagulation is of secondary importance. Low-dose oral Xa inhibitors are convenient and are thought to have a lower risk of bleeding; they are less suitable if there is a higher risk for recurrence. For cancer-associated VTE, we now prefer full-dose oral Xa inhibitors over low-molecular-weight heparin, with gastrointestinal lesions being a relative contraindication. Graduated compression stockings are not routinely indicated after DVT, but are encouraged if there is persistent leg swelling or if a trial of stockings improves symptoms. Medications have a limited role in the treatment of postthrombotic syndrome. After PE, patients should have clinical surveillance for chronic thromboembolic pulmonary hypertension (CTEPH), with ventilation-perfusion scanning and echocardiography being the initial diagnostic tests if CTEPH is a concern. Patients with CTEPH and other symptomatic patients with extensive residual perfusion defects should be evaluated for endarterectomy, balloon pulmonary angioplasty, or vasodilator therapies.
Topics: Anticoagulants; Humans; Postthrombotic Syndrome; Recurrence; Risk Factors; Time Factors; Venous Thromboembolism
PubMed: 31917402
DOI: 10.1182/blood.2019002364