scholarly journals Therapeutic Plasma Exchange for Urgent Rivaroxaban Reversal

2018 ◽  
Vol 45 (2) ◽  
pp. 96-98 ◽  
Author(s):  
Varun Kumar ◽  
Joseph Allencherril ◽  
Arthur Bracey ◽  
Alice J. Chen ◽  
Wilson W. Lam
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Exchange ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Therapeutic Plasma Exchange ◽  
Donor Kidney ◽  
Ischemic Time ◽  
Cold Ischemic Time

Direct oral anticoagulants, which include the factor Xa inhibitor rivaroxaban, have some advantages over vitamin K antagonists in regard to stroke prevention in patients with atrial fibrillation. However, no antidotes to reverse the effect of oral anticoagulants are commercially available, which can complicate treating patients in whom reversal is urgent. We faced this challenge in a kidney transplant candidate, a 65-year-old man with end-stage renal disease who had been taking rivaroxaban for paroxysmal atrial fibrillation. When a deceased-donor kidney became available, we needed to rapidly reduce the patient's bleeding risk, while minimizing the cold ischemic time of the donor kidney. Therefore, we decided to take an experimental approach and perform therapeutic plasma exchange. The patient's plasma anti-factor Xa level decreased from 0.4 IU/mL immediately before treatment to 0.21 IU/mL afterward, indicating that rivaroxaban had been actively removed from circulation. Waste fluid showed significant anti-Xa activity, indicating that the risk of rebound anticoagulation had been mitigated. The patient subsequently underwent successful kidney transplantation. To our knowledge, this is the first report of therapeutic plasma exchange to reverse the effects of rivaroxaban in a patient undergoing urgent surgery. This treatment may also be suitable for patients who have life-threatening, large-volume bleeding, especially in the presence of substantial kidney or liver dysfunction.

scholarly journals Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board

2020 ◽  
Vol 28 (10) ◽  
pp. 504-513 ◽  
Author(s):  
B. A. Mulder ◽  
J. ten Berg ◽  
H. ten Cate ◽  
N. van Es ◽  
M. E. W. Hemels ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Treatment Guidelines ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Daily Practice ◽  
Advisory Board ◽  
Vascular Surgeon ◽  
Clinical Scenarios

Abstract The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

scholarly journals Stroke-prevenció időskorban: az edoxabán hatékonysága és biztonságossága idős betegekben az ENGAGE AF vizsgálat eredményei alapján

2018 ◽  
Vol 159 (20) ◽  
pp. 798-802
Author(s):  
László Márk
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
The Elderly ◽  
Thromboembolic Events ◽  
Systemic Embolization ◽  
Number Of Patients ◽  
Net Clinical Benefit

Abstract: Atrial fibrillation is the most common clinically relevant arrhythmia frequently causing systemic thromboembolic events. Traditionally vitamin K antagonists had been used for decades to prevent these events. The emerging of the new direct anticoagulants has revolutionized this treatment and a gradual growth and extensive spread of usage is expected. The latest one approved in Hungary, edoxaban, is a factor Xa inhibitor. Once-daily administration and favourable safety profile are major benefits of this drug. In a large clinical study with a high number of patients it proved to be at least as effective as warfarin in the prevention of stroke and systemic embolization while causing significantly less major bleedings. As the incidence of atrial fibrillation increases with age, the observation that, compared with the other direct oral anticoagulants, the administration of edoxaban in the elderly has a favourable net clinical benefit (in the rate of prevented thromboembolic events and the number of caused bleedings) may have a great importance. Orv Hetil. 2018; 159(20): 798–802.

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.

scholarly journals Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Alok Dabi ◽  
Aristides P. Koutrouvelis
Keyword(s):  
Side Effects ◽  
Intracranial Hemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Reversal Agents ◽  
United States Food ◽  
Life Threatening

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

scholarly journals Optimal Anticoagulation Strategy for Cardioversion in Atrial Fibrillation

2015 ◽  
Vol 4 (1) ◽  
pp. 44 ◽  
Author(s):  
Philipp Bushoven ◽  
Sven Linzbach ◽  
Mate Vamos ◽  
Stefan H Hohnloser ◽  
◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Prospective Trial ◽  
Bleeding Complications ◽  
Order Of Magnitude ◽  
Pharmacological Cardioversion

For many patients with symptomatic atrial fibrillation, cardioversion is performed to restore sinus rhythm and relieve symptoms. Cardioversion carries a distinct risk for thromboembolism which has been described to be in the order of magnitude of 1 to 3 %. For almost five decades, vitamin K antagonist therapy has been the mainstay of therapy to prevent thromboembolism around the time of cardioversion although not a single prospective trial has formally established its efficacy and safety. Currently, three new direct oral anticoagulants are approved for stroke prevention in patients with non-valvular atrial fibrillation. For all three, there are data regarding its usefulness during the time of electrical or pharmacological cardioversion. Due to the ease of handling, their efficacy regarding stroke prevention, and their safety with respect to bleeding complications, the new direct oral anticoagulants are endorsed as the preferred therapy over vitamin K antagonists for stroke prevention in non-valvular atrial fibrillation including the clinical setting of elective cardioversion.

scholarly journals The Severity of Intracranial Hemorrhages Measured by Free Hemoglobin in the Brain Depends on the Anticoagulant Class: Experimental Data

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Kyle M. Ware ◽  
Douglas L. Feinstein ◽  
Israel Rubinstein ◽  
Prudhvi Battula ◽  
Jose Otero ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Hemoglobin Concentration ◽  
Thrombin Inhibitor ◽  
Free Hemoglobin ◽  
Intracranial Hemorrhages ◽  
The Brain

Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor). Brain hemorrhages were assessed by the free hemoglobin concentration in the brain parenchyma. Results. Vitamin K antagonists (warfarin and brodifacoum) significantly increased free hemoglobin in the brain. Among direct oral anticoagulants, thrombin inhibitor dabigatran also significantly increased free hemoglobin in the brain, whereas treatment with factor Xa inhibitor rivaroxaban did not have significant effect on the free hemoglobin concentration. Conclusions. Our data indicates that the severity of brain hemorrhages depends on the anticoagulant class and it is more pronounced with vitamin K antagonists.

scholarly journals Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Ali Zalpour ◽  
Thein Hlaing Oo
Keyword(s):  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Current Evidence ◽  
Thrombin Inhibitor ◽  
Prevention And Treatment ◽  
Financial Impacts

Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed.

scholarly journals Safety and timing of resuming dabigatran after major gastrointestinal bleeding reversed by idarucizumab

2018 ◽  
Vol 6 ◽  
pp. 2050313X1775333 ◽  
Author(s):  
Gian Galeazzo Riario Sforza ◽  
Francesco Gentile ◽  
Fabio Stock ◽  
Francesco Caggiano ◽  
Enrica Chiocca ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Case Report ◽  
Major Bleeding ◽  
Acute Treatment ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Oral Vitamin ◽  
Bleeding Events ◽  
Massive Rectal Bleeding

The recent introduction of direct oral anticoagulants, including rivaroxaban, dabigatran, apixaban, and edoxaban, for the acute treatment and secondary prevention of venous thromboembolism and in atrial fibrillation has been shown to provide greater clinical benefit than oral vitamin K antagonists. However, direct oral anticoagulants are associated with adverse events, the most common being major bleeding; such events require the reversal of the anticoagulant effects by specific agents. In this case report, we describe an 87-year-old female with atrial fibrillation treated with dabigatran who had massive rectal bleeding. Idarucizumab 5 g (2 × 2.5 g/50 mL) was successfully used to reverse dabigatran effect; subsequent to this, treatment with dabigatran was resumed, and there were no further bleeding events. This suggests that dabigatran can be safely restarted after major bleeding, but this outcome needs to be confirmed in studies involving larger groups of patients.

The NOACs: clinical pharmacology

ESC CardioMed ◽  
2018 ◽  
pp. 268-272
Author(s):  
Jeffrey Weitz
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Active Site ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
High Affinity

The limitations of vitamin K antagonists prompted the development of new oral anticoagulants that could be administered in fixed doses without routine coagulation monitoring. Focusing on thrombin and factor Xa because of their prominent roles in coagulation, structure-based design led to the development of small molecules that bind to the active site pockets of these enzymes with high affinity and specificity. Four non-vitamin K antagonist oral anticoagulants are now licensed: dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In phase III randomized clinical trials that included over 100,000 patients these agents have proven to be at least as effective as vitamin K antagonists for prevention of stroke in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism, and to produce less bleeding, particularly less intracranial bleeding.

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