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Anaesthesiology Intensive Therapy 2021Direct oral anticoagulants (DOACs) have revolutionized the field of anticoagulation in the last decade, mainly due to their fixed dosing, rapid onset of anticoagulant... (Review)
Review
Direct oral anticoagulants (DOACs) have revolutionized the field of anticoagulation in the last decade, mainly due to their fixed dosing, rapid onset of anticoagulant effect, and non-inferiority to vitamin K antagonists for both efficacy and safety. Also, the availability of specific and non-specific reversal agents makes these drugs popular. However, in critically ill patients, significant alterations in drug pharmacokinetics and pharmacodynamics might occur due to various ongoing pathophysiological derangements like decreased gastrointestinal absorption, increased volume of distribution, and impaired renal and/or hepatic function. Insight into these changes is essential regarding the safe and effective use of DOACs in critically ill patients. The current article is a narrative review on the use of DOACs in intensive care unit patients, covering 'Applied pharmacology'; the second article in the series covers 'Clinical evidence'.
Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Humans; Intensive Care Units
PubMed: 34816705
DOI: 10.5114/ait.2021.110607 -
Clinical and Applied... Sep 2017Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Factors such as the presence of transient risk factors for VTE, risk of bleeding,... (Review)
Review
Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Factors such as the presence of transient risk factors for VTE, risk of bleeding, and location of deep vein thrombosis (DVT) determine the duration of anticoagulation. Extended anticoagulation is offered to patients with unprovoked pulmonary embolism (PE) or proximal DVT and a low risk of bleeding. Anticoagulation for 3 months is advised in patients with provoked DVT or PE, high risk of bleeding, and isolated distal or upper extremity DVT. In patients with unprovoked PE or proximal DVT and a low risk of bleeding, who want to stop anticoagulation after 3 months, further risk stratification is necessary. Clinical scoring system, and thrombophilia testing otherwise not routinely performed, may be considered to measure risk of annual recurrence in such cases. Short-term anticoagulation may be considered in subsegmental PE and superficial vein thrombosis, particularly if patients are at low risk of bleeding and have persistent risk factors for recurrent VTE. In cases of catheter-associated thrombosis, the catheter need not be removed routinely, and the patient may be anticoagulated for 3 months or longer if the catheter is maintained in patients with cancer. Extensive screening for occult cancer in cases of unprovoked VTE is not beneficial. New oral anticoagulants such as apixaban, rivaroxaban, or dabigatran may be preferred to vitamin K antagonists in patients without cancer or renal failure, more so after the development of reversal agents such as idarucizumab and andexanet alfa.
Topics: Algorithms; Anticoagulants; Disease Management; Humans; Risk Assessment; Venous Thromboembolism
PubMed: 27268941
DOI: 10.1177/1076029616652727 -
British Journal of Haematology Oct 2013Orally active small molecules that selectively and specifically inhibit coagulation serine proteases have been developed for clinical use. For some patients these oral... (Review)
Review
Orally active small molecules that selectively and specifically inhibit coagulation serine proteases have been developed for clinical use. For some patients these oral direct inhibitors (ODIs) offer substantial benefits over oral vitamin K antagonists (VKA). However, for the majority of patients with good anticoagulant control with VKAs the advantages of the ODIs are primarily convenience and few drug interactions. The drugs are prescribed at fixed dose without the need for monitoring or dose adjustment in the majority of patients and the rapid onset of anticoagulation and short half-life make initiation and interruption of anticoagulation considerably easier than with VKAs. As yet, specific antidotes to ODIs are not available for clinical use but these are in development as rapid reversal agents. As with all anticoagulants produced so far, there is a correlation between intensity of anticoagulation and bleeding. Consequently, the need to consider the balance of benefit and risk in each individual patient is no less important than with VKA therapy. Dabigatran and rivaroxaban have been chosen for this review as examples of a thrombin inhibitor and an inhibitor of factor Xa respectively. The clinical application of these drugs is the focus of the review.
Topics: Administration, Oral; Anticoagulants; Antithrombins; Benzimidazoles; Dabigatran; Drug Interactions; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Rivaroxaban; Stroke; Thiophenes; beta-Alanine
PubMed: 23937286
DOI: 10.1111/bjh.12502 -
Journal of the American College of... Apr 2015Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy,... (Review)
Review
Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation.
Topics: Anticoagulants; Atrial Fibrillation; Disease Management; Humans; Risk Factors
PubMed: 25835447
DOI: 10.1016/j.jacc.2015.01.049 -
Stroke Jun 2017The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism.
METHODS
We searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes.
RESULTS
Eight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25-0.45; =5.12, for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58-1.77; =24.68, for heterogeneity <0.001). No significant publication bias was detected in our analyses.
CONCLUSIONS
In observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk-benefit profile of anticoagulation resumption after ICH.
Topics: Anticoagulants; Humans; Intracranial Hemorrhages; Myocardial Infarction; Stroke
PubMed: 28416626
DOI: 10.1161/STROKEAHA.116.016327 -
Journal of the American College of... Feb 2014Stroke prevention in patients with atrial fibrillation is a growing clinical dilemma as the incidence of the arrhythmia increases and risk profiles worsen. Strategies in... (Review)
Review
Stroke prevention in patients with atrial fibrillation is a growing clinical dilemma as the incidence of the arrhythmia increases and risk profiles worsen. Strategies in patients with nonvalvular atrial fibrillation have included anticoagulation with a variety of drugs. Knowledge that stroke in this setting typically results from thrombus in the left atrial appendage has led to the development of mechanical approaches, both catheter-based and surgical, to occlude that structure. Such a device, if it were safe and effective, might avoid the need for anticoagulation and prevent stroke in the large number of patients who are currently not treated with anticoagulants. Regulatory approval has been difficult due to trial design challenges, balance of the risk-benefit ratio, specific patient populations studied, selection of treatment in the control group, and specific endpoints and statistical analyses selected. Accumulating data from randomized trials and registries with longer-term follow-up continues to support a role for left atrial appendage exclusion from the central circulation as an alternative to anticoagulation in carefully-selected patient populations.
Topics: Anticoagulants; Atrial Appendage; Atrial Fibrillation; Clinical Trials as Topic; Hemorrhage; Humans; Prostheses and Implants; Risk Assessment; Stroke
PubMed: 24076495
DOI: 10.1016/j.jacc.2013.08.1631 -
Blood May 2008For more than 60 years, heparin and coumarin have been mainstays of anticoagulation therapy. They are widely available, inexpensive, effective, and have specific... (Review)
Review
For more than 60 years, heparin and coumarin have been mainstays of anticoagulation therapy. They are widely available, inexpensive, effective, and have specific antidotes but are regarded as problematic because of their need for careful monitoring. In addition, coumarin has a delayed onset of action, interacts with many medications, has a narrow therapeutic window, and is paradoxically prothrombotic in certain settings (ie, can precipitate "coumarin necrosis"). Heparin may require monitoring of its therapeutic effect and can also cause thrombosis (heparin-induced thrombocytopenia/thrombosis syndrome). These limitations have led to the development of new anticoagulants with the potential to replace current agents. These newer agents fall into 2 classes, based on whether they are antithrombin dependent (low-molecular-weight heparin, fondaparinux) or antithrombin independent (direct inhibitors of factor Xa and thrombin [factor IIa]). This paper addresses newer anticoagulants, reviewing their efficacy and limitations, and focuses on the risk of major bleeding that may complicate their use. In contrast to heparin and coumarin, none of these newer agents has a specific antidote that completely reverses its anticoagulant effect. Available data on the efficacy and safety of current and experimental agents for anticoagulant reversal are reviewed, and a plan for management of anticoagulant-induced bleeding is presented.
Topics: Anticoagulants; Coumarins; Disease Management; Hemorrhage; Heparin; Humans; Risk
PubMed: 18309033
DOI: 10.1182/blood-2007-10-120543 -
Seminars in Dialysis 2010Unfractionated heparin (UFH) is the anticoagulant of choice for most maintenance hemodialysis units in the United States. Low molecular weight heparin (LMWH) is the norm... (Review)
Review
Unfractionated heparin (UFH) is the anticoagulant of choice for most maintenance hemodialysis units in the United States. Low molecular weight heparin (LMWH) is the norm in Western Europe, but is not approved for this indication in the United States. UFH is likely to remain the agent of choice in the United States because of its relative ease of use, safety, and low cost. Coating tubing and dialyzers with heparin is now possible, but systemic anticoagulation with heparin is usually still required. The additional cost of this innovation does not yet justify its use. Side effects of both UFH and LMWH include heparin-induced thrombocytopenia, hypertriglyceridemia, and hyperkalemia. It is uncertain whether osteoporosis is an important side effect, as vitamin D deficiency, secondary hyperparathyroidism, age, and debility are confounding factors. When UFH poses a risk or its use is contraindicated, e.g., after development of heparin-induced thrombocytopenia, the use of direct thrombin inhibitors, regional citrate anticoagulation, citrate dialysate, and heparin-free dialysis may be appropriate.
Topics: Anticoagulants; Coated Materials, Biocompatible; Heparin; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 21039876
DOI: 10.1111/j.1525-139X.2010.00770.x -
Pediatric Nephrology (Berlin, Germany) Oct 2012Despite advances in biomaterials and dialyzer design, thrombin generation occurs in the dialysis circuit because of platelet and leukocyte activation. As such,... (Review)
Review
Despite advances in biomaterials and dialyzer design, thrombin generation occurs in the dialysis circuit because of platelet and leukocyte activation. As such, anticoagulation is required by the majority of children for successful dialysis to prevent clotting in the venous air detector and the capillary dialyzer, particularly for small children with slower blood flow rates. For many years unfractionated heparin has been the standard anticoagulant of choice, but is now being challenged by low-molecular-weight heparins (LMWHs) because they are simple to administer and reliable, particularly as the cost differential has been eroded. Alternative, nonheparin anticoagulants are more frequently available, but are often restricted to special circumstances: patients at high risk of hemorrhage; heparin allergy; or heparin-induced thrombocytopenia. These nonheparin alternatives are significantly more expensive than heparins, and may add a degree of complexity, such as citrate, which is a regional anticoagulant, although citrate-containing dialysate may permit short anticoagulant-free dialysis sessions. Systemic anticoagulants required for immune-mediated, heparin-induced thrombocytopenia are expensive and either have short half-lives, and therefore require continuous infusions, or prolonged half-lives, which, although allowing simple bolus administration, increases the risk of drug accumulation, over-dosage and hemorrhage.
Topics: Age Factors; Anticoagulants; Blood Coagulation; Child; Child, Preschool; Coated Materials, Biocompatible; Equipment Design; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant; Patient Selection; Practice Guidelines as Topic; Renal Dialysis; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 22374405
DOI: 10.1007/s00467-012-2129-5 -
The Journal of Extra-corporeal... Sep 2017Unfractionated heparin (UFH) is the most widely used injectable medication in the United States. UFH is a poly-dispersed, relatively impure combination of many... (Review)
Review
Unfractionated heparin (UFH) is the most widely used injectable medication in the United States. UFH is a poly-dispersed, relatively impure combination of many polysaccharides known as a glycosaminoglycan. It is used as the primary anticoagulant for heart surgery as well as for active treatment of deep venous thrombosis, vascular thrombosis, stroke, and many other potentially catastrophic clotting syndromes. Many perfusionists and cardiac team members know little of the biology of UFH other than its use for cardiopulmonary bypass. UFH is very similar to heparin sulfate, found on the surface of endothelial cells. Heparan sulfate protects endothelial surfaces from inflammatory attack and serves as a mechano-transducer for vascular shear. UFH and all glycosaminoglycans have far reaching pleotropic actions. This review elaborates on some of fascinating unique biology of these polysaccharides. Perhaps a number of the complex complications attributed to CPB are either caused by, or set up to occur by the complicated biology of UFH?
Topics: Anticoagulants; Blood Coagulation; Cardiopulmonary Bypass; Endothelial Cells; Glycocalyx; Heparin; Humans; Thrombosis
PubMed: 28979043
DOI: No ID Found