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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 -
Trends in Cardiovascular Medicine Feb 2020Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial... (Review)
Review
Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial fibrillation. However, blocking elements of the clotting cascade carries an inherent risk of bleeding. Also, anticoagulated patients sometimes require urgent surgery or invasive procedures. This has led to the emergence of a body of scientific literature on the reversal of anticoagulation in these two settings. Traditionally, vitamin K antagonists (VKAs), which indirectly inactivate clotting factors II, VII, IX and X (and natural anticoagulant proteins C and S), had been the mainstay of oral anticoagulation for half a century. Only a few years ago, the US Food and Drug Administration (FDA) approved a specific VKA reversal agent, 4-Factor Prothrombin Complex Concentrate (4F-PCC). The last decade has seen the rise of non-Vitamin K oral anticoagulants (NOACs), which target specific factors, i.e. Factors IIa and Xa. Investigators have rapidly developed reversal agents for these agents as well, idarucizumab for the Factor IIa inhibitor dabigatran (Pradaxa) and andexanet alfa for the entire class of Factor Xa inhibitors (FXaIs), currently four drugs: rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa) and betrixaban (Bevyxxa). Clinicians still use off-label PCC for reversing FXaIs in some settings, and a universal reversal agent, ciraparantag, remains in development. This review summarizes the safety and efficacy of these reversal agents in the setting of anticoagulant-associated major bleeding and the need for urgent surgery.
Topics: Administration, Oral; Anticoagulants; Antidotes; Atrial Fibrillation; Blood Coagulation; Blood Loss, Surgical; Clinical Decision-Making; Coagulants; Drug Administration Schedule; Humans; Perioperative Care; Postoperative Hemorrhage; Risk Assessment; Risk Factors; Stroke; Treatment Outcome; Venous Thromboembolism
PubMed: 30952383
DOI: 10.1016/j.tcm.2019.03.004 -
Journal of the American Heart... Jul 2020Direct oral anticoagulants (DOACs) have quickly become attractive alternatives to the long-standing standard of care in anticoagulation, vitamin K antagonist. DOACs are... (Review)
Review
Direct oral anticoagulants (DOACs) have quickly become attractive alternatives to the long-standing standard of care in anticoagulation, vitamin K antagonist. DOACs are indicated for prevention and treatment of several cardiovascular conditions. Since the first approval in 2010, DOACs have emerged as leading therapeutic alternatives that provide both clinicians and patients with more effective, safe, and convenient treatment options in thromboembolic settings. With the expanding role of DOACs, clinicians are faced with increasingly complex decisions relating to appropriate agent, duration of treatment, and use in special populations. This review will provide an overview of DOACs and act as a practical reference for clinicians to optimize DOAC use among common challenging scenarios. Topics addressed include (1) appropriate indications; (2) use in patients with specific comorbidities; (3) monitoring parameters; (4) transitioning between anticoagulant regimens; (5) major drug interactions; and (6) cost considerations.
Topics: Administration, Oral; Blood Coagulation; Clinical Decision-Making; Comorbidity; Cost-Benefit Analysis; Drug Costs; Drug Interactions; Drug Monitoring; Drug Substitution; Factor Xa Inhibitors; Hemorrhage; Humans; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32538234
DOI: 10.1161/JAHA.120.017559 -
Advances in Therapy Jan 2023Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent conditions with a significant healthcare burden, and represent the main indications for... (Review)
Review
Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent conditions with a significant healthcare burden, and represent the main indications for anticoagulation. Direct oral anticoagulants (DOACs) are the first choice treatment of AF/VTE, and have become the most prescribed class of anticoagulants globally, overtaking vitamin K antagonists (VKAs). Compared to VKAs, DOACs have a similar or better efficacy/safety profile, with reduced risk of intracerebral hemorrhage (ICH), while the risk of major bleeding and other bleeding harms may vary depending on the type of DOAC. We have critically reviewed available evidence from randomized controlled trials and observational studies regarding the risk of bleeding complications of DOACs compared to VKAs in patients with AF and VTE. Special patient populations (e.g., elderly, extreme body weights, chronic kidney disease) have specifically been addressed. Management of bleeding complications and possible resumption of anticoagulation, in particular after ICH and gastrointestinal bleeding, are also discussed. Finally, some suggestions are provided to choose the optimal DOAC to minimize adverse events according to individual patient characteristics and bleeding risk.
Topics: Humans; Aged; Atrial Fibrillation; Venous Thromboembolism; Anticoagulants; Cerebral Hemorrhage; Gastrointestinal Hemorrhage; Administration, Oral; Rivaroxaban; Stroke; Dabigatran
PubMed: 36244055
DOI: 10.1007/s12325-022-02333-9 -
Journal of the American College of... Aug 2020
2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Solution Set Oversight Committee.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiology; Consensus; Hemorrhage; Humans; Societies, Medical; United States
PubMed: 32680646
DOI: 10.1016/j.jacc.2020.04.053 -
Journal of Clinical Research in... Feb 2020This article reviews the current understanding and management of abnormal uterine bleeding (AUB) in adolescents. It is hoped that this review will provide readers with... (Review)
Review
This article reviews the current understanding and management of abnormal uterine bleeding (AUB) in adolescents. It is hoped that this review will provide readers with an approach to the evaluation and treatment of mild to severe uterine bleeding. AUB is a common problem which has significantly adverse effects on an affected adolescent’s quality of life. The most common underlying condition in AUB in adolescence is anovulation. During the evaluation, pregnancy, trauma and sexually transmitted diseases must be ruled out, regardless of history. It should be kept in mind that AUB during this period may be the first sign of underlying bleeding disorders. Although observation is sufficient in the mild form of AUB, at the other end of the spectrum life-threatening bleeding may necessitate the use of high doses of combined oral contraceptives, intravenous estrogen and/or interventional procedures.
Topics: Adolescent; Diagnosis, Differential; Female; Humans; Intrauterine Devices; Menstrual Cycle; Physical Examination; Quality of Life; Uterine Hemorrhage
PubMed: 32041387
DOI: 10.4274/jcrpe.galenos.2019.2019.S0200 -
The Israel Medical Association Journal... Mar 2022Pulmonary embolism (PE) is very common in cancer patients and is a marker of increased mortality in these patients. Treatment is associated with increased rates of... (Review)
Review
Pulmonary embolism (PE) is very common in cancer patients and is a marker of increased mortality in these patients. Treatment is associated with increased rates of recurrent thrombosis and bleeding and has undergone significant change in the last years with the increasing use of direct oral anticoagulants. Diagnosis of PE and risk stratification is possible with minor changes to existing risk scores. Thrombolytic therapy should be considered in appropriate patients.
Topics: Anticoagulants; Hemorrhage; Humans; Neoplasms; Pulmonary Embolism; Thrombolytic Therapy
PubMed: 35347932
DOI: No ID Found -
Journal of the American College of... Oct 2019Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist as they share multiple risk factors, including hypertension, diabetes mellitus, and coronary... (Review)
Review
Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist as they share multiple risk factors, including hypertension, diabetes mellitus, and coronary artery disease. Although there is irrefutable evidence supporting anticoagulation in AF in the general population, these data may not be transferable to the setting of advanced CKD, where the decision to commence anticoagulation poses a conundrum. In this cohort, there is a progressively increased risk of both ischemic stroke and hemorrhage as renal function declines, complicating the decision to initiate anticoagulation. No definitive clinical guidelines derived from randomized controlled trials exist to aid clinical decision-making, and the findings from observational studies are conflicting. In this review, the authors outline the pathophysiological mechanisms at play and summarize the limited existing data related to anticoagulation in those with concomitant CKD and AF. Finally, the authors suggest how to approach the decision of whether and how to use oral anticoagulation in these patients.
Topics: Administration, Oral; Anticoagulants; Arrhythmias, Cardiac; Atrial Fibrillation; Blood Coagulation; Brain Ischemia; Cardiology; Hemorrhage; Humans; Kidney Failure, Chronic; Patient Safety; Randomized Controlled Trials as Topic; Renal Dialysis; Risk; Risk Factors; Stroke
PubMed: 31648714
DOI: 10.1016/j.jacc.2019.08.1031 -
Frontiers in Immunology 2020Monocytes and macrophages are major cellular components of the innate immunity that play essential roles in tissue homeostasis. The contribution of different subsets of... (Comparative Study)
Comparative Study
Monocytes and macrophages are major cellular components of the innate immunity that play essential roles in tissue homeostasis. The contribution of different subsets of monocytes/macrophages to periodontal health and disease has not been fully elucidated. Type 2 diabetes mellitus (T2DM) is a risk factor for periodontitis. We hypothesized that the monocyte/macrophage signaling is perturbed in periodontitis-affected sites versus periodontally healthy sites and that this perturbation plays a critical role in the pathogenesis of periodontitis. Pairs of gingival tissue samples (each from a periodontally healthy and a periodontitis-affected site of the same patient) were harvested from 27 periodontitis patients, with and without T2DM. Each sample was processed to form a single-cell suspension, and a flow-cytometry panel was designed and validated to study monocyte and macrophage phenotypes. In separate experiments, the transcriptional changes associated with a pro-inflammatory phenotype were also examined in monocyte/macrophage subsets obtained from peripheral blood of patients with T2DM versus diabetes-free controls. A significantly higher proportion of intermediate (CD14CD16) monocytes was observed in periodontitis-affected tissues compared to healthy tissues. These monocytes overexpressed HLA-DR and PDL1 molecules, suggesting their activated inflammatory status. PDL1 increase was specific to intermediate monocytes. The ratio of M1/M2 macrophages was also significantly higher in periodontally affected sites, signifying an imbalance between inflammatory and repair mechanisms. We found a significantly higher expression of PDL1 in overall monocytes and M1 macrophages in periodontitis-affected sites compared to controls. Importantly, we identified a subpopulation of M1 macrophages present in periodontally affected tissues which expressed high levels of CD47, a glycoprotein of the immunoglobulin family that plays a critical role in self-recognition and impairment of phagocytosis. Analysis of the transcriptional landscape of monocytes/macrophages in gingival tissue of T2DM patients with periodontitis revealed a significant disruption in homeostasis toward a proinflammatory phenotype, elevation of pro-inflammatory transcription factors STAT1 and IRF1, and repression of anti-inflammatory JMJD3 in circulating monocytes. Taken together, our results demonstrate disruption of myeloid-derived cell homeostasis in periodontitis, with or without T2DM, and highlight a potentially significant role of these cell types in its pathogenesis. The impact of macrophage and monocyte signaling pathways on the pathobiology of periodontitis should be further evaluated.
Topics: B7-H1 Antigen; CD47 Antigen; Cells, Cultured; Diabetes Mellitus, Type 2; GPI-Linked Proteins; Gingiva; Gingival Hemorrhage; HLA-DR Antigens; Homeostasis; Humans; Immunity, Innate; Inflammation; Lipopolysaccharide Receptors; Macrophages; Monocytes; Periodontitis; Receptors, IgG; Signal Transduction; Transcription Factors
PubMed: 32210958
DOI: 10.3389/fimmu.2020.00330