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.

P690Incidence of events between vitamin K antagonists and direct oral anticoagulants in patients with cancer

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Pardo Sanz ◽  
L M Rincon ◽  
G De Lara ◽  
A Tamayo ◽  
L C Belarte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Systemic Embolism ◽  
Bleeding Events ◽  
Patients With Cancer

Abstract Background Balance between embolic and bleeding risk is challenging in patients with cancer. There is a lack of specific recommendations for the use of antithrombotic therapy in oncologic patients with atrial fibrillation (AF). We aimed to evaluate the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) within patients with breast cancer. We also compared the embolic and bleeding risk, the preventive management and the incidence of events between patients with and without cancer. Methods It is an ambispective observational multicentric study that analysed patients with non-valvular AF treated in Oncology and Cardiology Departments in Spain in the period 2011–2018. A total of 1237 female patients with AF were enrolled: 637 with breast cancer and 599 without cancer. The incidence of thromboembolic and major bleeding events according to the antithrombotic strategy with VKAs or DOACs was evaluated in the cohort of 637 patients with cancer. Analysis were conducted using SPSS software V.22.0 and R V.3.5.1, with a two-tailed significance value of 0.05. Results Mean follow-up was 3.1 years. Both groups were similar in age, CHA2DS2-VASc and HASB-LED scores. There was no evidence that the incidence of ischemic stroke/systemic embolism differed between patients with cancer treated with AVK and DOAC after CHA2DS2-VASc adjustment: HR 0.91 (95% CI, 0.42–1.99). In addition, no significant differences in the incidence of major bleeding events were found between DOACs and VKA after adjustment for HAS-BLED score: HR 1.53 (95% CI, 0.93–2.53) (Figure 3). Gastrointestinal bleeding was the main source of haemorrhages in both groups (45% of bleedings among patients treated with DOACs and, 37% in VKAs group). Metastatic disease or active chemotherapy were studied as potential covariates but none of them posed any relevant change in the result. Kaplan-Meier analysis Conclusions Cancer patients treated with DOACs did not differ versus those treated with VKAs with regards to stroke or systemic embolism in a model adjusted for CHA2DS2-VASc. Neither significant differences were found for bleeding events in a model adjusted for baseline HASBLED.

Bleeding risk with rivaroxaban compared with vitamin K antagonists in patients aged 80 years or older with atrial fibrillation

Heart ◽  
2020 ◽  
pp. heartjnl-2020-317923 ◽  
Author(s):  
Olivier Hanon ◽  
Jean-Sébastien Vidal ◽  
George Pisica-Donose ◽  
Galdric Orvoën ◽  
Jean-Philippe David ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Propensity Score ◽  
Vitamin K ◽  
Lower Risk ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Matched Sample ◽  
Intracerebral Bleeding

ObjectiveDirect oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is still missing. We compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients with non-valvular atrial fibrillation (AF) aged ≥80 years.MethodsWe performed a sequential observational prospective cohort study, using data from 33 geriatric centres. The sample comprised 908 patients newly initiated on VKAs between September 2011 and September 2014 and 995 patients newly initiated on rivaroxaban between September 2014 and September 2017. Patients were followed up for up to 12 months. One-year risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients with propensity score matching and Cox models.ResultsMajor bleeding risk was significantly lower in rivaroxaban-treated patients (7.4/100 patient-years) compared with VKA-treated patients (14.6/100 patient-years) after multivariate adjustment (HR 0.66; 95% CI 0.43 to 0.99) and in the propensity score–matched sample (HR 0.53; 95% CI 0.33 to 0.85). Intracerebral bleeding occurred less frequently in rivaroxaban-treated patients (1.3/100 patient-years) than in VKA-treated patients (4.0/100 patient-years), adjusted HR 0.59 (95% CI 0.24 to 1.44) and in the propensity score–matched sample HR 0.26 (95% CI 0.09 to 0.80). Major lower bleeding risk was largely driven by lower risk of intracerebral bleeding.ConclusionsOur study findings indicate that bleeding risk, largely driven by lower risk of intracerebral bleeding, is lower with rivaroxaban than with VKA in stroke prevention in patients ≥80 years old with non-valvular AF.

scholarly journals Reversal of Oral Anticoagulants for Intracerebral Hemorrhage Patients: Best Strategies

2017 ◽  
Vol 38 (06) ◽  
pp. 726-736 ◽  
Author(s):  
Lanting Fuh ◽  
Jonathan Sin ◽  
Joshua Goldstein ◽  
Bryan Hayes
Keyword(s):  
Intracerebral Hemorrhage ◽  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Quality Data ◽  
Reversal Agent ◽  
Intravenous Vitamin ◽  
Time Of Presentation

AbstractIn patients with acute intracerebral hemorrhage (ICH), one of the major concerns is ongoing bleeding or ICH expansion. Anticoagulated patients are at higher risk of ongoing expansion and worse outcome. It may be that rapid anticoagulation reversal can reduce the risk of expansion and improve clinical outcome. For those taking coumarins, the best available evidence suggests that intravenous vitamin K combined with four-factor prothrombin complex concentrate (4F-PCC) is the most rapid and effective regimen to restore hemostasis. For those on dabigatran, the highest quality data available for reversal are for idarucizumab, although it is not yet clear whether patients derive clinical benefit from this reversal. In the absence or failure of idarucizumab, activated prothrombin complex concentrate (aPCC) is recommended. For those on factor Xa inhibitors, the ideal reversal agent is not clear. Many providers use 4F-PCC or aPCC, but more specific agents are in clinical trials and may soon be available. In addition, the half-lives of the non–vitamin K antagonists are relatively short compared with warfarin, and so some patients may not have a clinically relevant coagulopathy at the time of presentation. Overall, the optimal reversal agent, when one is required, is a function of which anticoagulant the patient is taking.

Reversal strategies in patients treated with direct oral anticoagulants

VASA ◽  
2019 ◽  
Vol 48 (5) ◽  
pp. 389-392 ◽  
Author(s):  
Paul Gressenberger
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Study Data ◽  
Current Evidence ◽  
Bleeding Complications ◽  
Bleeding Events ◽  
Reversal Agent

Summary. Administration of direct oral anticoagulants (DOACs) for the treatment of venous thrombotic events (VTE) or non-valvular atrial fibrillation (AF) is now standard of care and has demonstrated clinical efficacy and safety in numerous clinical studies. Usually these substances have lower overall mortality and less risk of cerebral hemorrhage, but depending on the substance and study, they are more likely to cause gastrointestinal bleeding than vitamin K antagonists (VKA), the medication that used to be standard for VTE and AF. Since DOACs have very short plasma elimination half-lives compared to VKA, for most bleeding events, expert opinions suggest that withdrawal of DOACs and supportive care will likely suffice to stop a bleeding episode. Because there is a bleeding risk associated with DOACs, reversal strategies may be needed if a patient receiving DOAC therapy bleeds during surgery or an invasive procedure. So far, idarucizumab has been the only available antidote that binds specifically to dabigatran and safely and quickly reverses its anticoagulant effects. Idarucizumab has no effects on anti Xa inhibitors or other anticoagulants. To date, treatment of serious, life-threatening bleeds in patients with anti-Xa-inhibitor has involved 4 factor prothrombin complex concentrates (PCC). PCC restores normal hemostasis laboratory values in most patients with major bleeding events after anti Xa inhibitor intake. Recently, the US Food and Drug Administration (FDA) approved andexanet alfa as the first specific antidote for the anti-Xa inhibitors apixaban and rivaroxaban. So far clinical experience with this substance and data comparing it with PCC are lacking. Currently ciraparantag is under investigation as a universal reversal agent for all DOACs and low molecular weight heparin as well. Because it is so broadly applicable, ciraparantag might be a good future option for the management of most bleeding complications under anticoagulant treatment. The aim of this review is to summarize recent study data and recommendations on nonspecific and specific DOAC reversal strategies and to present the current evidence.

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.

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