Vitamin K antagonists, direct oral anticoagulants, and the rationale for reversal agents

2016 ◽  
Vol 73 (10_Supplement_2) ◽  
pp. s3-s4 ◽  
Author(s):  
Michael P. Gulseth
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Reversal Agents

scholarly journals Direct Oral Anticoagulants after Ischemic Stroke: Which Patient? Which Drug? And How Early?

2021 ◽  
Vol 41 (01) ◽  
pp. 031-034
Author(s):  
Gian Marco De Marchis
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Vitamin K ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Reversal Agents

AbstractDirect oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and ischemic stroke. The main advantage of DOAC over VKA is the lower rate of bleeding and mortality. This review covers challenges clinicians can encounter when treating patients with AF and ischemic stroke, including timing of DOAC start and ongoing randomized clinical trials, appropriate dosing, and available comparative evidence across DOACs. For patients without AF but with an ischemic stroke, the review outlines the role of DOACs. Finally, the risk of thrombotic events associated with specific DOAC reversal agents and DOAC pausing is reviewed.

Direct oral anticoagulants (DOAC) – Management of emergency situations

2017 ◽  
Vol 37 (04) ◽  
pp. 257-266 ◽  
Author(s):  
Edelgard Lindhoff-Last
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Emergency Operations ◽  
Reversal Agents ◽  
Life Threatening

SummaryThe worldwide increase in the aging population and the associated increase in the prevalence of atrial fibrillation and venous thromboembolism as well as the widespread use of direct oral anticoagulants (DOAC) have resulted in an increase of the need for the management of bleeding complications and emergency operations in frail, elderly patients, in clinical practice. When severe bleeding occurs, general assessment should include evaluation of the bleeding site, onset and severity of bleeding, renal function, and concurrent medications with focus on anti-platelet drugs and nonsteroidal anti-inflammatory drugs (NSAID). The last intake of the DOAC and its residual concentration are also relevant. The site of bleeding should be immediately localized, anticoagulation should be interrupted, and local measures to stop bleeding should be taken. In life-threatening bleeding or emergency operations immediate reversal of the antithrombotic effect may be indicated. If relevant residual DOAC-concentrations are expected and surgery cannot be postponed, prothrombin complex concentrate (PCC) and/or a specific antidote should be given. While idarucizumab, the specific antidote for dabigatran, has been recently approved for clinical use, the recombinant factor X protein andexanet alfa, an antidote for the reversal of inhibitors of coagulation factor Xa, and ciraparantag, a universal antidote, are not available. Future cohort studies are necessary to assess the efficacy and safety of specific and unspecific reversal agents in “real-life” conditions. This was the rationale for introducing the RADOA-registry (RADOA: Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists), a prospective non-interventional registry, which will evaluate the effects of specific and unspecific reversal agents in patients with life-threatening bleeding or emergency operations either treated with DOACs or vitamin K antagonists.

scholarly journals Direct Oral Anticoagulants and Vitamin K Antagonists: Role in Thrombotic Damage, Safety, and Indications

2021 ◽  
Author(s):  
Mohammed Aldhaeefi ◽  
Abdulrahman Alshaya ◽  
Khalid Bin Saleh ◽  
Omar Alshaya ◽  
Hisham Badreldin
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Dosage Forms ◽  
Reversal Agents ◽  
Clinical Indications

This chapter is intended to discuss the available oral anticoagulants, including vitamin K antagonists and the Direct Oral Anticoagulants such as dabigatran, apixaban, rivaroxaban, and edoxaban. It will review their basic pharmacology, pharmacokinetics, pharmacodynamics, dosage forms, clinical indications, and place in therapy. Finally, this chapter will also discuss the currently available reversal agents.

Anticoagulation and Reversal Agents

2018 ◽  
Author(s):  
Sarah Culbreth ◽  
Dirk Varelmann ◽  
Jessica Rimsans
Keyword(s):  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Fresh Frozen Plasma ◽  
Reversal Agent ◽  
Reversal Agents ◽  
Fresh Frozen

Managing the balance between bleeding risk and the need to treat thromboembolic disease continues to challenge anesthesiologists and interventionalists, particularly as new direct oral anticoagulants (DOAC) are approved for use. While in the hospital, patients are often placed on parenteral anticoagulants that require monitoring to ensure the dynamic changes that occur in acute illness do not lead to excessive or insufficient anticoagulation. Until recently, vitamin K antagonists (VKA) have been the mainstay of therapy in patients with atrial fibrillation and venous thromboembolism. To facilitate procedures and or minimize bleeding, VKAs were either held or its effects reversed by vitamin K, fresh frozen plasma, or four-factor prothrombin complex concentrate to facilitate procedures and minimize bleeding. Those patients on DOACs continue to challenge the interventionist as there is no commercially available targeted reversal agent for all DOACs. When anticoagulation reversal is warranted, timing or urgency of reversal, the mechanism of action of the anticoagulant, half-life of the anticoagulant, risk of bleeding associated with the procedure, end-organ function, and the patient’s risk factors for thrombosis and bleeding should be considered. This chapter briefly reviews anticoagulants and reversal strategies. This review contains 1 figure, 10 tables, and 53 references. Key Word: activated prothrombin complex concentrate, anticoagulation, antithrombotic, life-threatening bleeding, reversal, periprocedural, prothrombin complex concentrate, surgery

Perioperative Management of Patients Receiving New Anticoagulants

2019 ◽  
Vol 25 (19) ◽  
pp. 2149-2157 ◽  
Author(s):  
Massimo Lamperti ◽  
Andrey Khozenko ◽  
Arun Kumar
Keyword(s):  
Vitamin K ◽  
Elective Surgery ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Oral Intake ◽  
Bleeding Risk ◽  
Dietary Vitamin ◽  
Reversal Agent ◽  
Onset Of Action ◽  
Reversal Agents

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

scholarly journals Falls in ED patients: do elderly patients on direct oral anticoagulants bleed less than those on vitamin K antagonists?

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Martin Müller ◽  
Ioannis Chanias ◽  
Michael Nagler ◽  
Aristomenis K. Exadaktylos ◽  
Thomas C. Sauter
Keyword(s):  
Elderly Patients ◽  
Vitamin K ◽  
Intracranial Haemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Complications ◽  
Lower Odds ◽  
Anticoagulated Patients ◽  
Proportional Incidence

Abstract Background Falls from standing are common in the elderly and are associated with a significant risk of bleeding. We have compared the proportional incidence of bleeding complications in patients on either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA). Methods Our retrospective cohort study compared elderly patients (≥65 years) on DOAC or VKA oral anticoagulation who presented at the study site – a Swiss university emergency department (ED) – between 01.06.2012 and 01.07.2017 after a fall. The outcomes were the proportional incidence of any bleeding complication and its components (e.g. intracranial haemorrhage), as well as procedural and clinical parameters (length of hospital stay, admission to intensive care unit, in-hospital-mortality). Uni- and multivariable analyses were used to compare the studied outcomes. Results In total, 1447 anticoagulated patients were included – on either VKA (n = 1021) or DOAC (n = 426). There were relatively more bleeding complications in the VKA group (n = 237, 23.2%) than in the DOAC group (n = 69, 16.2%, p = 0.003). The difference persisted in multivariable analysis with 0.7-fold (95% CI: 0.5–0.9, p = 0.014) lower odds for patients under DOAC than under VKA for presenting with any bleeding complications, and 0.6-fold (95% 0.4–0.9, p = 0.013) lower odds for presenting with intracranial haemorrhage. There were no significant differences in the other studied outcomes. Conclusions Among elderly, anticoagulated patients who had fallen from standing, those under DOACs had a lower proportional incidence of bleeding complications in general and an even lower incidence of intracranial haemorrhage than in patients under VKAs.

Direct Anticoagulants Versus Vitamin K Antagonists in Patients Aged 80 Years or Older With Atrial Fibrillation in a “Real-world” Nationwide Registry: Insights From the FANTASIIA Study

2020 ◽  
Vol 25 (4) ◽  
pp. 316-323
Author(s):  
Martín Ruiz Ortiz ◽  
Javier Muñiz ◽  
María Asunción Esteve-Pastor ◽  
Francisco Marín ◽  
Inmaculada Roldán ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Real World ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Left Ventricular ◽  
Anticoagulant Treatment ◽  
Cancer History

Objective: To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Methods: A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, observational, multicenter study. Basal features, embolic events (stroke and systemic embolism), severe bleedings, and all-cause mortality at follow up were investigated according to the anticoagulant treatment received. Results: Mean age was 84.0 ± 3.4 years, 56% were women. Direct oral anticoagulants were prescribed to 123 (21.3%) patients. Compared with 455 (78.7%) patients treated with VKAs, those treated with DOACs presented a lower frequency of permanent AF (52.9% vs 61.6%, P = .01), cancer history (4.9% vs 10.9%, P = .046), renal failure (21.1% vs 32.2%, P = .02), and left ventricular dysfunction (2.4% vs 8.0%, P = .03); and higher frequency of previous stroke (26.0% vs 16.6%, P = .02) and previous major bleeding (8.1% vs 3.6%, P = .03). There were no significant differences in Charlson, CHA2DS2VASc, nor HAS-BLED scores. At 3-year follow up, rates of embolic events, severe bleedings, and all-cause death (per 100 patients-year) were similar in both groups (DOACs vs VKAs): 0.34 vs 1.35 ( P = .15), 3.45 vs 4.41 ( P = .48), and 8.2 vs 11.0 ( P = .18), respectively, without significant differences after multivariate analysis (hazard ratio [HR]: 0.25, 95% confidence interval [CI]: 0.03-1.93, P = .19; HR: 0.88, 95% CI: 0.44-1.76, P = .72 and HR: 0.84, 95% CI: 0.53-1.33, P = .46, respectively). Conclusion: In this “real-world” registry, the differences in major events rates in octogenarians with AF were not statistically significant in those treated with DOACs versus VKAs.

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