Management Of Direct Oral Anticoagulants Research Articles

Decision Algorithms for Direct Oral Anticoagulant Use in Patients With Nonvalvular Atrial Fibrillation: A Practical Guide for Neurologists.

Direct oral anticoagulants (DOACs) are valid alternative options to vitamin K antagonists due to their limited interactions with drugs or food and the fact that they do not require regular coagulation monitoring. To this regard, recent practice guidelines recommend that DOACs should be considered as first-line anticoagulant therapy for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). This review (1) outlines current international guidelines for the management of DOACs to prevent stroke in patients with NVAF, (2) outlines indications for elderly patients as well as specific settings including acute coronary syndromes and intracranial hemorrhage, and (3) offers a practical guide for the use of DOACs in neurological settings.

Incorporating Comprehensive Management of Direct Oral Anticoagulants into Anticoagulation Clinics.

Anticoagulation clinics emerged as a means to optimize warfarin effectiveness and minimize bleeding risks. Anticoagulation clinics have traditionally been warfarin-based models due to the need for frequent blood-level monitoring, drug interactions, dietary considerations, and periprocedural management with warfarin. These models have demonstrated improved anticoagulation control and reduced bleeding complications for patients taking warfarin. Direct oral anticoagulants (DOACs) emerged with the perception of improved convenience due to the lack of blood-level monitoring and lack of dietary considerations. Despite the advantages of DOAC therapy, new challenges exist with their management, warranting ongoing monitoring. Such challenges include prescribing and dosing issues, drug adherence, drug interactions, and high drug cost. Comprehensive anticoagulation centers are needed to manage and monitor all oral anticoagulants including DOACs. The objectives of this review are to describe the challenges and opportunities that exist in the management of DOACs and to describe a practice model that integrates a DOAC management service into the traditional anticoagulation clinic.

Sa1032 Appropriate and Safe Management of Direct Oral Anticoagulants in Endoscopic Resection of Colorectal Polyps

Sa1032 Appropriate and Safe Management of Direct Oral Anticoagulants in Endoscopic Resection of Colorectal Polyps

Managing the perioperative patient on direct oral anticoagulants.

Patients are increasingly treated with direct oral anticoagulants (DOACs) for the prevention of stroke due to non-valvular atrial fibrillation and for the treatment of venous thromboembolism. When these patients present for urgent or emergent surgical procedures, they present a challenge to the anesthesiologist who must manage perioperative risk due to anticoagulation. The purpose of this module is to review the literature surrounding the perioperative management of DOACs. Timing, laboratory monitoring, and availability of reversal agents are important considerations to optimize patients being treated with DOACs who require emergent surgery. Laboratory tests are not recommended for routine monitoring of DOACs since they do not correlate well with anticoagulant activity. Most widely available laboratory tests lack the sensitivity to detect anticoagulant effects at low plasma concentrations. However, a normal thrombin time for dabigatran excludes clinically significant drug levels. If the risk of bleeding is judged to be high because of a recent dose of DOAC, various options are available to mitigate bleeding. When possible, surgery should be delayed for at least 12 hr after the last dose of DOAC. Activated charcoal may mitigate the anticoagulant effect caused by DOACs if administered less than two hours after the drug was ingested. Four-factor prothrombin complex concentrates (PCCs) may be useful to reduce life-threatening bleeding associated with factor Xa inhibitors. Activated PCCs have been shown to reverse abnormal coagulation tests associated with all DOACs, but there is a lack of reported evidence of clinical benefit. Idarucizumab is a specific antidote that is effective for reversal of anticoagulation due to dabigatran. An antidote for rivaroxaban and apixaban (andexanet alfa) as well as a universal antidote for all DOACs and heparin (PER977) are in clinical development. Perioperative management of anticoagulation due to DOACs is a growing concern as the number of patients prescribed these medications increases each year. These patients can be safely optimized for urgent or emergent surgery by giving appropriate consideration to timing, monitoring, and reversal agents.

Utilization and prescribing patterns of direct oral anticoagulants

BackgroundScant literature exists evaluating utilization patterns for direct oral anticoagulants (DOACs).ObjectivesThe primary objective was to assess DOAC prescribing in patients with venous thromboembolism (VTE) and nonvalvular atrial fibrillation (NVAF) in outpatient clinics. Secondary objectives were to compare utilization between family medicine (FM) and internal medicine (IM) clinics, characterize potentially inappropriate use, and identify factors associated with adverse events (AEs).MethodsThis was a retrospective cohort study of adults with NVAF or VTE who received a DOAC at FM or IM clinics between 10/19/2010 and 10/23/2014. Descriptive statistics were utilized for the primary aim. Fisher’s exact test was used to evaluate differences in prescribing using an adapted medication appropriateness index. Logistic regression evaluated factors associated with inappropriate use and AEs.ResultsOne-hundred twenty patients were evaluated. At least 1 inappropriate criterion was met in 72 patients (60.0%). The most frequent inappropriate criteria were dosage (33.0%), duration of therapy (18.4%), and correct administration (18.0%). Apixaban was dosed inappropriately most frequently. There was no difference in dosing appropriateness between FM and IM clinics. The odds of inappropriate choice were lower with apixaban compared to other DOACs (odds ratio [OR]=0.088; 95% confidence interval [CI] 0.008–0.964; p=0.047). Twenty-seven patients (22.5%) experienced an AE while on a DOAC, and the odds of bleeding doubled with each inappropriate criterion met (OR=1.949; 95% CI 1.190–3.190; p=0.008).ConclusionPotentially inappropriate prescribing of DOACs is frequent with the most common errors being dosing, administration, and duration of therapy. These results underscore the importance of prescriber education regarding the appropriate use and management of DOACs.

Gastrointestinal bleeding secondary to the new anticoagulants.

To quantify direct oral anticoagulants (DOACs) related gastrointestinal bleeding (GIB), characterize patients at greatest risk and provide a pragmatic approach for the management of these drugs. This review will also summarize risk-management strategies and highlight evolving areas of clinical knowledge. DOACs permit anticoagulation with predictable dosing without the need for routine serum monitoring. Since their availability on the market, they have quickly emerged as a popular alternative for patients requiring short-term and lifelong anticoagulation. However, they are associated with an increased risk of GIB when compared with warfarin; thus, gastroenterologists must be prepared to manage DOAC-related GIB and prevent drug-related complications. This review will focus on acute and elective periendoscopic DOAC management, high-risk clinical groups for DOAC-related GIB, quantification of DOAC levels, use of reversal agents and minimization of thromboembolic risk associated with temporary interruption. This review will highlight pragmatic strategies for the treatment of DOAC-related bleeding and the prevention of postendoscopic DOAC bleeding. It will address new and evolving areas of periendoscopic management and identify knowledge gaps requiring further research to inform clinical practice.

Postoperative bleeding and coagulation disorders

New data have been made available in the field of haemostasis and thrombosis. Some long-awaited answers to important questions have been published, and some debates have benefited from an updated perspective. Two important domains are addressed in this update: massive bleeding (1/1/1 ratios and fibrinogen concentrates) and the management of direct oral anticoagulants (monitoring and antidotes). Both are highly controversial topics. Higher plasma/platelets/red blood cells units ratios are now partly supported by a new study in trauma. Several studies show that preemptive doses of fibrinogen do not appear to bring any benefit. Monitoring of direct oral anticoagulants is now possible, and it has to be recommended in some circumstances. Specific antidotes are being developed, but there are still more questions than answers. These new data should help anaesthesiologists and intensivists to better understand and manage massively bleeding patients or direct oral anticoagulants treated patients.

Prevention of Gastrointestinal Bleeding in Patients Receiving Direct Oral Anticoagulants

The direct oral anticoagulants (DOACs) have quickly become popular choices for convenient stroke and thromboembolism protection. Popularity of this new anticoagulant class is driven by their predictable fixed dosing without the necessity for serum monitoring of anticoagulant effect. However, this convenience must be balanced against the risk of gastrointestinal (GI) bleeding. Age >65 years, hepatorenal dysfunction, low body weight, concomitant prescription of antiplatelet agents, or non-steroidal anti-inflammatory drugs, and drugs that interact with P-glycoprotein or the cytochrome P450 system, can influence therapeutic effectiveness of DOACs and increase the risk of GI bleeding. In this state-of-the-science review, these aforementioned risks are explored, as is DOAC pharmacology and the potential for drug, dietary, and herbal supplement interaction. Current best practice recommendations for peri-endoscopic DOAC management and temporary interruption are reviewed. The utility of existing risk-prediction scores and other practical risk-management strategies, based on specific patient characteristics, are highlighted. Finally, pragmatic advice to enhance GI and cardiology dialogue, patient education, and shared decision-making regarding DOAC prescription is provided.

Management of direct oral anticoagulants-associated bleeding in the trauma patient.

This article emphasizes the differentiated management of direct oral anticoagulants (DOACs)-associated bleeding in trauma patients to generate a severity adjusted treatment protocol. The management of DOAC-associated bleeding should take severity, mortality risk, and haemodynamic effects of the trauma-induced bleeding into account. The different pharmacological properties of DOACs are important for the management of trauma-induced bleeding. Comorbidities like renal impairment and liver dysfunction prolong their half-life. Patients with minor bleeding in stable clinical condition can be managed by a 'wait and see' approach. Moderate bleeding is suggested to be managed by a primarily conservative approach. In life-threatening bleeding, the administration of activated or nonactivated factor concentrates seems justified, together with supportive measures as part of an advanced management protocol. The administration of specific antidotes may be an alternative in the future. A monoclonal antibody to dabigatran (idarucizumab) has recently been approved by the Food and Drug Administration, whereas antidotes to Factor X activated inhibitors (andexanet and aripazine) are still under development. Sufficiently powered studies with clinical and safety outcome measures are still missing for all specific antidotes at this time.

Abstract 167: Impact of a Pharmacist-Led Outpatient Direct Oral Anticoagulation Service

Background: Direct oral anticoagulants (DOACs) represent novel alternatives to vitamin K antagonists but present new challenges for appropriate prescribing and ongoing patient adherence. We assessed the impact of a pharmacist-led DOAC service on prescription appropriateness and patient adherence as compared to usual care. Methods: We performed a retrospective, observational, matched cohort analysis of patients prescribed a DOAC at a large academic medical center between September 20, 2013 and December 31, 2014. We compared a group of patients (n=129) who participated in a pharmacist-led DOAC service to a matched group (n=129) who received usual care using coarsened exact matching based on prescriber specialty, DOAC prescribed, indication for anticoagulation and age. Co-primary endpoints included the percentage of patients who had appropriate DOAC therapy (FDA-approved medication and dose based on indication and renal function) prescribed at baseline and at 3-6 month follow up after initiating the medication. Secondary endpoints included mean medication possession ratios (MPR) for patients who received at least 3 months of DOAC therapy and had available pharmacy records (n=171). We performed multivariable logistic regression modeling for appropriate prescription and multivariable linear regression modeling for MPR. Results: Patients in the two groups were well balanced across multiple demographic and comorbid factors. Patients in the pharmacist-led DOAC service were significantly more likely to have an appropriate combination of DOAC and dose prescribed for their indication at baseline as compared to usual care (92.2% vs. 77.5%; adjusted odds ratio [aOR] 3.02, p=0.006). This finding persisted at follow up (93.7% vs. 81.1%; aOR=2.92, p=0.016). There was no significant difference between groups in the number of patients determined to have an appropriate DOAC prescribed for an FDA-approved indication (independent of dose) in the pharmacist-led service (95.3%) vs usual care (93.0%) at baseline (aOR 0.93, p=0.901). Patients in the pharmacist-led service had a mean adjusted MPR of 91.8% compared to 79.3% with usual care (p=0.001) over a median follow up of 248 days. Conclusions: A pharmacist-led DOAC service increases appropriate dosing of DOACs at baseline and follow up as well as patient adherence to therapy. Associated costs and clinical event rates associated with pharmacist-lead DOAC management remain to be investigated.

Periprocedural Management of Direct Oral Anticoagulants: Comment on the 2015 American Society of Regional Anesthesia and Pain Medicine Guidelines.

Periprocedural Management of Direct Oral Anticoagulants: Comment on the 2015 American Society of Regional Anesthesia and Pain Medicine Guidelines.

Myths and Legends

Diagnostic bronchoscopy for obtaining tissue samples is a commonly performed procedure and is an extremely useful diagnostic tool for malignant and benign conditions. A significant proportion of patients who undergo these procedures are anticoagulated for conditions including atrial fibrillation, pulmonary embolism, and deep-vein thrombosis. With new classes of oral anticoagulants being prescribed more frequently, it is important that bronchoscopists are comfortable in the management of direct oral anticoagulants in the perioperative period.

Peri-procedural management of dabigatran and rivaroxaban: Duration of anticoagulant discontinuation and drug concentrations

BackgroundPeri-procedural management of direct oral anticoagulants (DOAC) is challenging. The optimal duration of pre-procedural discontinuation that guarantees a minimal DOAC concentration ([DOAC]) at surgery is unknown. The usual 48-hour discontinuation might not be sufficient for all patients. ObjectivesTo test the hypothesis that a 48-hour DOAC discontinuation is not sufficient to ensure a minimal per-procedural [DOAC], defined as [DOAC]<30ng/mL. To investigate the factors associated with per-procedural [DOAC]. To evaluate the ability of normal PT and aPTT to predict [DOAC]<30ng/mL. MethodsPatients treated with dabigatran or rivaroxaban, and requiring any invasive procedure were included in this multicentre, prospective, observational study. [DOAC], PT and aPTT were measured during invasive procedure. ResultsSixty-five patients were enrolled. Duration of DOAC discontinuation ranged from 1-168h. Per-procedural [DOAC] ranged from <30 to 466ng/mL. [DOAC]<30ng/mL occurred more frequently after 48-hour discontinuation than after a shorter delay. [DOAC] remained ≥30ng/mL in 36% and 14% of measurements performed 24-48h and 48h-120h after discontinuation, respectively. According to ROC curve, a cut-off value of 120hours for DOAC discontinuation had a better specificity than a cut-off value of 48hours to predict [DOAC]<30ng/mL. Normal PT and aPTT ratios had good specificity and positive predictive value, but limited sensitivity (74%) and negative predictive value (73%) to predict [DOAC]<30ng/mL. ConclusionsA 48-hour discontinuation does not guarantee a [DOAC]<30ng/mL in all patients. Normal PT and aPTT are flawed to predict this threshold and could not replace specific assays. Further studies are needed to define the relationship between per-procedural [DOAC] and clinical outcomes.

Management of Direct Oral Anticoagulants in the Perioperative Setting

From the Department of Anesthesia, Institut Mutualiste Montsouris, Paris, France. Address reprint requests to Ivan Philip, Service d’Anesthesie, Institut Mutualiste Montsouris, 42, Boulevard Jourdan, 75674 Paris Cedex 14, France. E-mail: ivan.philip@imm.fr © 2015 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.12.019

FEIBA™ for Reversal of Direct Oral Anticoagulant Associated Major Bleeding

▪Introduction: Direct oral anticoagulants (DOACs) are indicated for the prevention of systemic embolism in patients with atrial fibrillation and for the prevention and treatment of venous thrombosis. Although DOACs offer advantages over the vitamin K antagonists, some hesitancy remains over their use given the lack of specific antidotes for management of life threatening bleeding events. In vivo studies, case reports and case series have shown that prothrombin complex concentrate (PCC) and activated PCC might potentially be used to control life threatening bleeding in patients with DOAC-associated bleeding episodes. Herein we describe management and outcomes of DOAC-associated life threatening bleeding events using an activated PCC (FEIBA™).Methods: A retrospective review of patients presenting with DOAC-associated (dabigatran, rivaroxaban or apixaban) life threatening bleeding to The Ottawa Hospital between January 2013 and June 2014 are included. Patients received 25 – 50 units/kg of FEIBA™. The primary outcome was adverse thrombotic and embolic events during follow-up. Secondary outcome was symptomatic control of bleeding.Results: Nine patients presented to hospital with life threatening bleeding episodes (post trauma: n=3; spontaneous bleeding: n=6). Spontaneous episodes included epistaxis or gastro-intestinal bleeding. Baseline characteristics are depicted in Table 1. A majority of patients had atrial fibrillation (n=8) and received rivaroxaban (n=5).The last dose of DOAC was taken within 24 hours of bleeding events for all patients. All patients received supportive management, interventions/procedures aimed at attaining source control of bleeding when possible, and transfusion of FEIBA™ for reversal of anticoagulant effect. Adverse events after receiving FEIBA™ were uncommon with one patient experiencing a TIA with expressive aphasia and visual field deficit on the evening of FEIBA™ transfusion; deficits resolved by the time of hospital discharge. Two patients with GI bleeding continued to have ongoing bleeding despite FEIBA™ administration and two patients died as a result of major bleeding.Conclusions: In this cohort of patients with major bleeding associated with DOACs, FEIBA™ administration, in addition to supportive care, was helpful in minimizing further complications of most bleeding events and associated with a low rate of adverse events. Prospective studies are needed to evaluate benefits and harms of FEIBA™ for management of DOAC associated major bleeding.Abstract 1540. Table 1:Patients with Life-threatening BleedingPatient (Age and Gender)Indication for DOAC [AF(CHADS2); VTE]DOAC and DosageSite of BleedingIntervention/ProcedureUnits of PRBCs TransfusedAdditional TreatmentFEIBA™ Dose (IU)(1st/2nd)Adverse Events post-FEIBA™ AdministrationSurvived Hospitalization85 MaleAF (2)Rivaroxaban 20 mg dailyEpistaxisNasal Packing0–3275–Yes86 MaleAF (2)Rivaroxaban 20 mg dailyLGIBAngiogram, no embolization performed10Vitamin K3159/ 2952–Yes84 MaleAF (2)Dabigatran 110 mg BIDOrbital vitreous hemorrhageSurgical repair of ruptured globe0–1812–Yes92 MaleAF (6)Apixaban 5 mg BIDLeft handConservative management1Tranexamic acid2718TIAYes85 MaleVTERivaroxaban 20 mg dailyLGIBConservative management2Vitamin K1740–Yes90 FemaleAF (5)Rivaroxaban 20 mg dailySDHConservative management0–3275–No; died of major bleed93 FemaleAF (6)Apixaban 2.5 mg BIDLGIBConservative management4–2241–No93 MaleAF (3)Rivaroxaban 15 mg dailyUGIBUpper endoscopy, no intervention4Vitamin K3000–No; died of major bleed and septic shock81 MaleAF (4)Dabigatran 110 mg BIDLGIBUpper endoscopy and colonoscopy, no interventions4–3362–NoAF = atrial fibrillation; BID = twice daily; CHADS = congestive heart failure, hypertension, age, diabetes, stroke; DOAC = direct oral anticoagulant; IU = international units; LGIB = lower gastrointestinal bleeding; PRBC = packed red blood cells; SDH = subdural hematoma; TIA = transient ischemic attack; UGIB = upper gastrointestinal bleeding; VTE = venous thromboembolism DisclosuresOff Label Use: FEIBA is an activated prothrombin complex concentrate that was used during management of life threatening bleeding in patients with direct oral anticoagulant-associated bleeding episodes..

Perioperatives Gerinnungsmanagement bei oraler Antikoagulation

The aim of the perioperative management of anticoagulation in patients with long-term oral anticoagulation is to minimize bleeding complications of surgical interventions. We aimed to give a summary of current data and to give practical recommendations for colleagues practicing surgery. This article gives a narrative overview of available data from 31 publications between 2000 and 2013. Every perioperative decision on whether to continue oral anticoagulation is preceded by an assessment of the risk of bleeding and embolism. In cases with a low risk of bleeding, oral anticoagulation can usually be continued. In contrast, for larger interventions with a moderate to high risk of bleeding, a discontinuation of phenprocoumon with temporary bridging is required. In this case it is common practice to discontinue phenprocoumon 7-9 days preoperatively and administer heparin mostly in the form of low molecular weight heparin (LMWH) depending on the international normalized ratio (INR). In contrast perioperative management of direct oral anticoagulants (DOAC) is discussed controversially. Based on the pharmacokinetics of the DAOC, the recommendations are to minimize the anticoagulation-free interval to 2-4 half-lives (HWZ) preoperatively (1-5 days) and early postoperative restart. In this case no bridging is necessary. On the other hand, an early interruption of DOAC 5 days prior to surgery to a minimum of 2 days postoperatively is favored by some surgeons to assure an adequate perioperative hemostasis. Depending on the risk of thromboembolism, bridging is required. These recommendations are justified by limited clinical experience and the absence of antagonism. The perioperative management of coagulation is still a challenge. While there are consolidated decision aids for phenprocoumon, the approach under DOAC treatment is still controversial due to limited data.