Direct Oral Anticoagulants Dosing Research Articles

Bleeding in Patients with Atrial Fibrillation Treated with Different Doses of Direct Oral Anticoagulants and Vitamin K Antagonists: A Population-Based Study

INTRODUCTIONRecent large randomized controlled trials have shown that direct oral anticoagulants (DOACs) are at least as effective as vitamin K antagonists (VKAs) for prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation (AF) and are associated with similar or lower rates of bleeding. The results for bleeding seen in Phase 3 trials might not be applicable to real world practice. Population-based studies suggest that the bleeding risk for DOACs and VKA is similar however neither the risk of bleeding associated with different doses of DOACs nor that associated with apixaban in routine clinical practice is well established. We performed a large population-based study to determine the incidence of bleeding in patients with AF beginning treatment with different doses of dabigatran, rivaroxaban, apixaban or a VKA.METHODSFrom the computerized database of the 4.5 million member Israeli Clalit Health Services health care provider, consecutive patients initiating a VKA or DOAC for AF between January 1, 2011 and December 31, 2014 were studied. Bleeding patients who required hospitalization were identified and key clinical and laboratory data were recorded. Incidence of bleeding was calculated during the first 20 months of treatment which was the minimum duration of treatment for all of the drugs. Adjusted hazard ratios for overall bleeding, intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding and all-cause mortality within 30 days were recorded and case fatality rates were calculated as the proportions of bleeding patients who died within 30 days.RESULTS26184 patients initiated anticoagulants for AF: 14258 received VKA, 214 -received dabigatran 75 mg, 3563 received dabigatran 110 mg , 1410 received dabigatran 150 mg, 2570 received rivaroxaban 15 mg, 2140 received rivaroxaban 20 mg, 1227 received apixaban 2.5 mg and 802 received apixaban 5 mg. Key patient demographics and the overall and site-specific bleeding rates are shown in table 1. Hazard ratios for any bleeding, ICH and GI bleeding adjusted for age, renal failure, CHADS2 score, aspirin use and Charlson comorbidity score favored dabigatran 150 mg versus VKA (P<0.05). The case fatality rate for VKA bleeding was 11,4%, dabigatran 110mg-10.5%, dabigatran 150 mg- 6.25%. rivaroxaban 15mg- 15.5%, rivaroxaban 20 mg- 10%, apixaban 2.5 mg- 11.4% and for apixaban 5mg-7.14%CONCLUSIONSThe results of our population-based non-randomized study of unselected AF patients demonstrate a decreased bleeding rate for dabigatran 150mg and an increased bleeding rate for apixaban 2.5 mg compared to VKA. There was a consistent tendency for increased bleeding in patients receiving lower versus higher doses of the NOACs which probably reflects physician tendency to select lower doses of DOACs for patients at greater risk for bleeding. [Display omitted] DisclosuresEllis:Boehringer Ingelheim: Speakers Bureau; Bayer: Speakers Bureau; Pfizer: Speakers Bureau. Eikelboom:Pfizer: Honoraria, Research Funding; Eli Lilly: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding; Bristol Myer Squibb: Honoraria, Research Funding; Sanofi-Aventis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

Safety of Doacs in Patients of Extreme Weight

▪Direct Oral Anticoagulants (DOACs), specifically factor Xa inhibitors, have been approved for VTE treatment, VTE prophylaxis after hip and knee replacement, and stroke prevention in non-valvular atrial fibrillation. The DOACs are fast replacing warfarin for these indications due to their ease of administration, fixed dosing, and fast onset and offset of action. However, there are no specific dosing recommendations for DOACs in patient with extreme body weight because these agents were not well represented in the clinical trials, and no specific trials examining safety or efficacy in patients of extreme weight have been conducted. A recent analysis of clinical trials data by the ISTH suggests that while data is limited, the available data suggests that DOACs are safe in patients less than 120 kg at standard doses, and are not recommended in patients greater than 120 kg unless specific concentration levels are obtained to assess their efficacy.To better understand the safety of DOACs in patients of extreme weights, we performed a retrospective analysis of a random sample of patients of low weight (<60 kg), normal weight (60-120 kg), and extreme weight (>120 kg). A random sample of 113 charts was extracted from the medical record; 34 patients were excluded due to missing data, and 79 patients were included with 27 in the <60 kg group, and 26 in both the normal and obese weight groups. Data was collected on patients from May 2011 through April 2016. Baseline patient characteristics, bleeding events, documented clot progression, and several laboratory values (hemoglobin, platelet count, creatinine and INR at commencement of anticoagulation, hemoglobin and INR at discharge or closest follow up appointment) were recorded. The outcomes assessed were rates of bleeding and clot progression.Thirty-five (44.30%) patients were male. The average age in each group was 64, 65, and 64, respectively. Forty-eight (60.76%) patients received apixaban, and the remaining patients were given rivaroxaban. Thirty-six (45.57%) patients received anticoagulation for atrial fibrillation, 26 (32.91%) had deep vein thrombosis, 13 (16.46%) had pulmonary embolism, and 4 (5.06%) had other reasons, such as peripheral arterial disease or arterial thrombus. In the low weight group, 9 patients had a documented bleeding episode (33.33%, p=0.1289), versus 4 patients in the normal weight group (15.38%) and 9 patients in the overweight group (27.85%, p=0.1091). There was no major bleeding in patients of normal weight but bleeding occurred in 4 in the underweight group 14.81%, p=.0413) and 3 in the overweight group (11.54%, p=.0744). In total, 22 of 79 patients (27.85%) had a bleeding episode. Two patients in the underweight group had clot progression (7.41%, p=0.9681), versus 2 patients in the normal weight group and no patients in the overweight group. There was no significant difference between patients who bled and those who did not bleed in creatinine, hemoglobin, platelet count or INR at the time of initiation of DOAC. We did not find a significant difference in rates of bleeding in low weight or overweight patients when compared to normal weight individuals; however there was a trend toward significance in both groups. Patients received either 5 mg bid of apixaban or 20 mg daily of rivaroxaban in both groups, therefore the difference was not attributable to different prescribing patterns. Neither group had a significant number of patients with clot progression. It is intriguing that both low weight and overweight patients had similar rates of bleeding (33.33 and 34.62%, respectively).The PK/PD data referenced by the ISTH raised the concern that overweight patients may actually be underdosed if given standard doses of DOACs. Our data, though limited by the small number of patients, poses very interesting and clinically relevant questions about DOAC use in both weight extremes: are we overdosing DOACs for underweight patients? Why are overweight patients bleeding at similar rates? We plan on formulating a prospective study to answer these questions, utilizing drug-specific peak and trough levels to ascertain sub-, supra-, and therapeutic levels in patients who bleed on DOAC therapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Association of BW with Thromboembolic and Bleeding Outcomes in Phase III Randomized Controlled Trials of Direct Oral Anticoagulants: Systematic Review and Meta-Analysis

Association of BW with Thromboembolic and Bleeding Outcomes in Phase III Randomized Controlled Trials of Direct Oral Anticoagulants: Systematic Review and Meta-Analysis

Inappropriate dosing of direct oral anticoagulants in patients with atrial fibrillation.

Atrial fibrillation (AF) is a common cardiovascular disease for which newer oral anticoagulants are available. The main objective of this study was to evaluate the appropriateness in prescriptions of direct oral anticoagulant (DOACs), more specifically apixaban, dabigatran and rivaroxaban. This was a singlecentre, retrospective study conducted in the province of Quebec, Canada. Adult subjects hospitalized between October 2011 and October 2014, with a diagnosis of AF, and a DOAC prescription were included. Data were retrieved from the electronic medical records and prescriptions were evaluated according to appropriateness criteria. A total of 500 subjects were included (235 subjects on dabigatran,222 on rivaroxaban and 43 on apixaban). Overall, 70.4% (95% confidence interval [Cl] 66.4-74.1) of DOAC prescriptions were considered appropriate. About 24% of subjects received an inappropriate dose of apixaban, dabigatran or rivaroxaban. A reduced dose was prescribed in 56.8% of subjects with no clearindication, and 43.2% received a dose that was not reduced while indicated. DOACs were frequentlyprescribed at a dose that was considered inappropriate. There is a need to strengthen dosing recommendations of DOACs in clinical practice.

Abstract 12918: Comparison between Standard and Reduced Doses of Direct Oral Anticoagulants for Periprocedural Anticoagulation in Truly Low Thromboembolic Risk Patients Undergoing Catheter Ablation of Atrial Fibrillation

Introduction: Direct oral anticoagulants (DOACs) are generally administered in truly low thromboembolic risk patients undergoing atrial fibrillation (AF) ablation. All DOACs have two dose settings, but reduced doses are commonly used in patients for whom a DOAC dose reduction is not necessary according to the dose reduction criteria in the real world. Purpose: This study aimed to evaluate the safety and efficacy of periprocedural DOACs in AF patients with a CHA 2 DS 2 -VASc score of 0 (male) or 1 (female), and compare that between standard and reduced DOAC doses. Methods: We retrospectively enrolled 1013 consecutive patients receiving periprocedural DOACs, and 232 patients (median, 54 years) with a CHA 2 DS 2 -VASc score of 0 (190 males) or 1 (42 females) were analyzed (dabigatran, n=36; rivaroxaban, n=121; apixaban, n=59; edoxaban, n=16). Standard and reduced doses were administered in 149 and 83 patients, respectively, but essentially a dose reduction was not necessary in 95.2% of the reduced dose patients. All DOACs were discontinued on the day of the procedure and no pre-ablation heparin bridging was performed. Results: The standard and reduced dose patients required a similar heparin dosage (median, 13630 vs. 13330 units, P=0.671), and the mean and maximum activated clotting times were 303 and 329 seconds with the standard doses, and 310 and 333 seconds with the reduced doses, respectively (P=0.012 and 0.076). No symptomatic thromboembolisms occurred. The incidence of major and minor bleeding and silent cerebral ischemic lesions on magnetic resonance imaging was 0.7%, 5.4%, and 10.0% with the standard doses and 0%, 1.2%, and 12.5% with the reduced doses, respectively (P=0.642, 0.107, and 0.558). The standard and reduced doses revealed a similar bleeding risk (2 with minor bleeding vs. 0; P=0.305) during the post-ablation oral anticoagulation (median, 106 days vs. 92 days; P=0.627). Conclusions: Standard and reduced DOAC doses for periprocedural anticoagulation revealed a similar thromboembolic and hemorrhagic risk in CHA 2 DS 2 -VASc low-risk patients undergoing AF ablation. A reduced dose use, if not according to the dose reduction criteria, may not contribute to either a reduction in bleeding or an increase in thromboembolisms associated with AF ablation.

Abstract 13053: HAS-BLED Score and Atrial Fibrillation Type as Risk Factors for Bleeding Complications Associated With Catheter Ablation of Atrial Fibrillation among Patients Receiving Direct Oral Anticoagulants

Purpose: This study aimed to identify predictors of thromboembolic and hemorrhagic events associated with catheter ablation of atrial fibrillation (AF) among patients receiving periprocedural direct oral anticoagulants (DOACs). Methods: We retrospectively studied 1034 consecutive AF patients (64±11 years; 777 males) receiving dabigatran (n=208), rivaroxaban (n=465), apixaban (n=292), or edoxaban (n=69) before AF ablation. The DOACs were continued in 61 (5.9%) patients and discontinued in 973 (94.1%) on the day of the procedure. No heparin bridging was performed before the ablation. During the procedure, heparin was given to maintain an activated clotting time (ACT) of 300-350 seconds. Major bleeding was defined as cardiac tamponade or pericardial effusions requiring drainage, intracranial and gastrointestinal hemorrhages, retroperitoneal bleeding, and bleeding requiring a blood transfusion, and vascular access site complications requiring intervention. Minor bleeding was defined as bleeding other than major bleeding. Results: No symptomatic thromboembolisms occurred. The incidence of major and minor bleeding was 0.6% and 8.8%, respectively, and did not significantly differ among the DOACs (P=0.351 and 0.177; Figure 1). In the multivariate logistic regression analysis, the HAS-BLED score and LSP-AF were significant positive predictors of bleeding complications (odds ratios, 1.358 and 1.956; 95% CIs, 1.108-1.665 and 1.196-3.198; P=0.003 and 0.007), but the DOAC type and dose (standard/reduced), periprocedural continuation of the DOACs, total heparin dosage, and intraprocedural ACT were not significant predictors. The periprocedural bleeding risk increased with higher HAS-BLED scores (Figure 2). Conclusions: Periprocedural DOAC treatment with adequate intraprocedural anticoagulation was effective in preventing symptomatic thromboembolisms. A higher HAS-BLED score and LSP-AF can be high risk factors for bleeding complications.

Direct oral anticoagulants in patients with atrial fibrillation and renal impairment, extremes in weight, or advanced age.

A growing number of patients with an indication for stroke prevention in atrial fibrillation have kidney-, age-, or weight-related alterations in pharmacokinetics that affect dosing of direct oral anticoagulants. Because these patients were excluded from or comprised a small number of patients in clinical trials, there is a lack of evidence to guide clinicians. As a consequence, many patients do not receive oral anticoagulation despite a high risk for atrial fibrillation-related stroke. Here, we present a review of direct oral anticoagulant pharmacokinetics and a review of the available clinical evidence in patients with weight-, kidney-, and age-related disease.

Potential Effect of Substituting Estimated Glomerular Filtration Rate for Estimated Creatinine Clearance for Dosing of Direct Oral Anticoagulants

To determine the potential effect of substituting glomerular filtration rate (GFR) estimates for renal clearance estimated using the Cockcroft-Gault method (CrCL-CG) to calculate direct oral anticoagulant (DOAC) dosing. Simulation and retrospective data analysis. Community, academic institution, nursing home. Noninstitutionalized individuals aged 19 to 80 from the National Health and Nutrition Examination Survey (NHANES) (2011/12) (n = 4,687) and medically stable research participants aged 25 to 105 (n = 208). Age, height, weight, sex, race, serum creatinine, CrCL-CG, and GFR (according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations). Outcome measures were dosing errors if GFR were to be substituted for CrCL-CG. Renal clearance estimates according to all methods were highly correlated (P < .001), although at lower clearances, substitution of GFR estimates for CrCL-CG resulted in failure to recognize needs for dose reductions of rivaroxaban or edoxaban in 28% of NHANES subjects and 47% to 56% of research subjects. At a CrCL-CG of less than 30 mL/min, GFR estimates missed indicated dosage reductions for dabigatran in 18% to 21% of NHANES subjects and 57% to 86% of research subjects. Age and weight contributed to differences between renal clearance estimates (P < .001), but correction of GFR for body surface area (BSA) did not reduce dosing errors. At a CrCL-CG greater than 95 mL/min, edoxaban is not recommended, and GFR esimates misclassified 24% of NHANES and 39% of research subjects. Correction for BSA reduced misclassification to 7% for NHANES and 14% in research subjects. Substitution of GFR estimates for estimated CrCl can lead to failure to recognize indications for reducing DOAC dose and potentially higher bleeding rates than in randomized trials.

Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant

All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0%) had a baseline creatinine clearance <50mL/min and 23 (12.2%) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1%) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9%) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

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.

Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines.

The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor): For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation);For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation).For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin: The advice for warfarin is fundamentally unchanged from BSG 2008 guidance. Direct Oral Anticoagulants (DOAC): For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation). For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥ 48 hours before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30 - 50 mL/min we recommend that the last dose of DOAC be taken 72 hours before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation).

Novel anticoagulants: general overview and practical considerations for dental practitioners.

Currently, 4 novel Direct Oral Anticoagulants (DOACs) were approved by the FDA. This review focuses on these agents and proposes a matrix for the general dentists to assess bleeding risk in dental management of patient on DOACs. The outline covers the pharmacology of DOACs (rivaroxaban, apixaban, edoxaban and dabigatran), bleeding complications, risk associated with discontinuation, monitoring/reversal, and implications for the dental practitioners. A total of 18 randomized controlled trials were identified with mixed results in regards to the risk for bleeding. Considering the pharmacology of DOACs and challenges in monitoring and reversing their effect, the dentist should consider carefully the management of patients on DOACs as it may differ from patients on conventional anticoagulants. Based on the type of dental procedure and the medical risk assessment, several general treatment approaches can be considered: continue DOACs, time dental treatment as late as possible after the last DOACs dose, discontinue DOACs for 24hrs, or discontinue DOACs for 48hrs. Based on the current reported dental literature, limited dental surgery may benefit from the first 2 conservative options. However, this needs to be proven in comparative clinical trials.

The criteria of the Italian Federation of Thrombosis Centres on DOACs: a "real world" application in nonvalvular atrial fibrillation patients already on vitamin K antagonist.

The aim of this study was to evaluate the number of patients with nonvalvular atrial fibrillation (NVAF), anticoagulated with vitamin K antagonists (VKA), and monitored in our Thrombosis Centre, who could replace VKA with direct oral anticoagulants (DOACs) based on the Italian Federation of Thrombosis Centres (FCSA) consensus criteria. A total of 525 NVAF patients treated with VKA were studied. Therapeutic range (TTR) assessment and a capillary test for serum creatinine measure were carried out. The patients' preference was evaluated through the administration of a dedicated questionnaire. A history of intracranial bleeding was also taken into account. DOACs would cover 29 % of the patients considering a TTR <70 %; the percentage falls to 10 % if a TTR <55 % is considered. Only 20 % of the patients would move from VKA to DOACs because of the lack of an antidote and laboratory checks during DOACs therapy. Thirty-three percent of patients were worried that they would forget to take the tablets twice a day. About 2 % of patients could not use DOACs since their glomerular filtration rate was less than 30 ml/min, while in 23.6 %, a reduction in the daily dose of DOACs would have been required due to renal failure. TTR assessment, renal function and a previous history of intracranial bleeding would reduce the percentage of patients who could switch from VKA to DOACs, but it is the patients' preference that strongly influences the percentage of those who would benefit from DOACs treatment. However, if laboratory controls were available, it would rise considerably.

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..