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      Comparison of Sampling Methods for International Normalized Ratio Monitoring in Haemodialysis Patients (INRHaemo Study)

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          Abstract

          Background: Haemorrhagic and thrombotic complications are common in dialysis patients on warfarin; thus, accurate international normalized ratio (INR) monitoring is critical. For expediency and patient comfort, blood sampling from the haemodialysis access or circuit is commonly performed. Point-of-care (POC) INR machines allow both peripheral vein preservation and rapid results, yet are not validated in the haemodialysis population. Methods: A prospective cohort study in haemodialysis patients taking warfarin was undertaken. Three paired samples were drawn over a single session: peripheral blood INR, POC INR, and dialysis INR. Agreement using Bland-Altman analysis and correlation coefficients between the peripheral blood INR, haemodialysis INR, and POC INR were calculated. Inappropriate dosing decisions based on haemodialysis or POC INR were quantified. Results: Amongst 34 patients, agreement between the dialysis INR and peripheral blood INR was high, with the haemodialysis INR differing from the peripheral INR by <±0.2, 85.2% of the time. Correlation between the 2 methods was high ( r = 0.914; p < 0.001). POC INR differed from peripheral INR values by <±0.2, 67.6% of the time, with less agreement at higher INR values. Dosing decisions were incongruent between the dialysis and peripheral INR in 6%, whilst the POC and peripheral INR disagreed in 26%. Conclusions: There was good agreement and correlation between the peripheral blood, haemodialysis access/circuit, and POC INR values. POC INR was less reliable at higher values, and dosing decisions differed from the peripheral INR in a quarter of cases.

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          Most cited references15

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          Kidney function influences warfarin responsiveness and hemorrhagic complications.

          Although management of warfarin is challenging for patients with chronic kidney disease (CKD), no prospective studies have compared response to warfarin among patients with minimal, moderate, and severe CKD. This secondary analysis of a prospective cohort of 578 patients evaluated the influence of kidney function on warfarin dosage, anticoagulation control, and risk for hemorrhagic complications. We adjusted all multivariable regression and proportional hazard analyses for clinical and genetic factors. Patients with severe CKD (estimated GFR 4; P = 0.052), compared with patients with no, mild, or moderate CKD. Patients with severe CKD had a risk for major hemorrhage more than double that of patients with lesser degrees of renal dysfunction (hazard ratio 2.4, 95% confidence interval 1.1 to 5.3). In conclusion, patients with reduced kidney function require lower dosages of warfarin, have poorer control of anticoagulation, and are at a higher risk for major hemorrhage. These observations suggest that warfarin may need to be initiated at a lower dosage and monitored more closely in patients with moderate or severe CKD compared with the general population. Diminished renal function may have implications for a larger proportion of warfarin users than previously estimated.
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            Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation.

            Oral anticoagulation therapy (OAT) is the choice treatment for thromboembolism prevention in atrial fibrillation (AF), although data about OAT use in haemodialysis (HD) patients with AF are contradictory.
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              Is Open Access

              Warfarin use and stroke, bleeding and mortality risk in patients with end stage renal disease and atrial fibrillation: a systematic review and meta-analysis

              Background Patients with end stage renal disease (ESRD), including stage 5 chronic kidney disease (CKD), hemodialysis (HD) and peritoneal dialysis (PD), are at high risk for stroke-related morbidity, mortality and bleeding. The overall risk/benefit balance of warfarin treatment among patients with ESRD and AF remains unclear. Methods We systematically reviewed the associations of warfarin use and stroke outcome, bleeding outcome or mortality in patients with ESRD and AF. We conducted a comprehensive literature search in Feb 2016 using key words related to ESRD, AF and warfarin in PubMed, Embase and Cochrane Library without language restriction. We searched for randomized trials and observational studies that compared the use of warfarin with no treatment, aspirin or direct oral anticoagulants (DOACs), and reported quantitative risk estimates on these outcomes. Paired reviewers screened articles, collected data and performed qualitative assessment using the Cochrane Risk of Bias Assessment Tool for Non-randomized Studies of Interventions. We conducted meta-analyses using the random-effects model with the DerSimonian - Laird estimator and the Knapp-Hartung methods as appropriate. Results We identified 2709 references and included 20 observational cohort studies that examined stroke outcome, bleeding outcome and mortality associated with warfarin use in 56,146 patients with ESRD and AF. The pooled estimates from meta-analysis for the stroke outcome suggested that warfarin use was not associated with all-cause stroke (HR = 0.92, 95 % CI 0.74–1.16) or any stroke (HR = 1.01, 95 % CI 0.81–1.26), or ischemic stroke (HR = 0.80, 95 % CI 0.58–1.11) among patients with ESRD and AF. In contrast, warfarin use was associated with significantly increased risk of all-cause bleeding (HR = 1.21, 95 % CI 1.01–1.44), but not associated with major bleeding (HR = 1.18, 95 % CI 0.82–1.69) or gastrointestinal bleeding (HR = 1.19, 95 % CI 0.81–1.76) or any bleeding (HR = 1.21, 95 % CI 0.99–1.48). There was insufficient evidence to evaluate the association between warfarin use and mortality in this population (pooled risk estimate not calculated due to high heterogeneity). Results on DOACs were inconclusive due to limited relevant studies. Conclusions Given the absence of efficacy and an increased bleeding risk, these findings call into question the use of warfarin for AF treatment among patients with ESRD.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2021
                March 2021
                08 February 2021
                : 52
                : 1
                : 17-25
                Affiliations
                [_a] aDepartment of Medicine, Campbelltown Hospital, Campbelltown, New South Wales, Australia
                [_b] bRenal Department, Liverpool Hospital, Liverpool, New South Wales, Australia
                [_c] cHaematology Department, Liverpool Hospital, Liverpool, New South Wales, Australia
                Author notes
                *Theepika Rajkumar, Department of Medicine, Campbelltown Hospital, Therry Road, Campbelltown, NSW 2560 (Australia), theepika.rajkumar@gmail.com
                Article
                513094 Am J Nephrol 2021;52:17–25
                10.1159/000513094
                33556938
                c96af392-8da0-4e44-8d68-e936fb43a5a4
                © 2021 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 22 September 2020
                : 15 November 2020
                Page count
                Figures: 2, Tables: 3, Pages: 9
                Categories
                Patient-Oriented, Translational Research: Research Article

                Cardiovascular Medicine,Nephrology
                International normalized ratio,Warfarin,Haemodialysis,Sampling,Point-of-care

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