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      Dalteparin Dosing in High-Flux Haemodialysis and Haemodiafiltration

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          Abstract

          Background: Low-molecular-weight heparins are being increasingly used as an alternative to unfractionated heparin for anticoagulation of the haemodialysis (HD) circuit. Data on dalteparin use in high-flux HD and haemodiafiltration (HDF) are limited. We examined the safety and efficacy of dalteparin in this setting to enable recommendations on the optimal dose range. Methods: This prospective study was conducted in a single dialysis unit. Subjects who had been receiving dalteparin for at least 10 HD sessions were studied. Anti-Xa activity was measured for all subjects at the start of the HD session, at 60 min into HD and at the end of dialysis. Results: 55 subjects were studied. None had detectable anti-Xa activity at the start of the session. Using adequacy criteria based on target anti-Xa activity >0.4 IU/ml at 1 h and <0.4 IU/ml at the end of dialysis, 39 (71%) patients had adequate anticoagulation, 12 (22%) patients were under-anticoagulated and 4 (7%) were over-anticoagulated. The mean dose in the adequately anticoagulated group was 60.7 ± 11.7 IU/kg, in the under-anticoagulated group 39.3 ± 9.6 IU/kg and in the over-anticoagulated group 70.1 ± 14.6 IU/kg. The optimal dose of dalteparin appears to be 60 ± 10 IU/kg, which facilitates the achievement of the target anti-Xa activity in the range of 0.4-0.75 IU/ml at 1 h and <0.4 IU/ml at the session end. Conclusion: Dalteparin is a safe and effective anticoagulant for patients on high-flux HD and HDF. The optimal dose appears to be 60 ± 10 IU/kg. The desirable target range of anti-Xa activity is 0.4-0.75 at 1 h and <0.4 IU/ml at the session end.

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          Effect of anticoagulation on blood membrane interactions during hemodialysis.

          Adequate anticoagulation is a precondition to prevent extracorporeal blood clotting and to improve biocompatibility during hemodialysis. In this study, we performed a morphologic analysis by using scanning electron microscopy to compare three modes of anticoagulation-conventional unfractionated heparin (UFH), low molecular weight heparin (LMWH; dalteparin sodium), or sodium citrate during hemodialysis-on membrane-associated coagulation activation. Fifteen patients on regular hemodialysis therapy were investigated. Five patients received UFH, five patients LMWH, and five patients sodium citrate as an anticoagulant during a standardized hemodialysis protocol using a single-use polysulfone capillary dialyzer. Membrane-associated clotting was evaluated using a scanning electron microscope. A dialyzer clotting score was used for quantitative description of coagulation activation on membrane segments. Using UFH as an anticoagulant revealed the most pronounced cell adhesion and thrombus formation and the highest dialyzer clotting score (11.5 +/- 1.3 of a maximal 20 points). LMWH had a lower dialyzer clotting score than UFH (10.4 +/- 1.2 of 20 points). During the use of sodium citrate, a negligible thrombus formation and the lowest dialyzer clotting score (1.6 +/- 0.6 of 20 points, P < 0.05) were observed. The results of this investigation indicate that using sodium citrate as an anticoagulant during hemodialysis induces a lower activation of coagulation than both conventional and fractionated heparin, which might contribute to an improvement of biocompatibility of hemodialysis extracorporeal circulation.
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            Unfractionated heparin for hemodialysis: still the best option.

            Unfractionated heparin (UFH) is the anticoagulant of choice for most maintenance hemodialysis units in the United States. Low molecular weight heparin (LMWH) is the norm in Western Europe, but is not approved for this indication in the United States. UFH is likely to remain the agent of choice in the United States because of its relative ease of use, safety, and low cost. Coating tubing and dialyzers with heparin is now possible, but systemic anticoagulation with heparin is usually still required. The additional cost of this innovation does not yet justify its use. Side effects of both UFH and LMWH include heparin-induced thrombocytopenia, hypertriglyceridemia, and hyperkalemia. It is uncertain whether osteoporosis is an important side effect, as vitamin D deficiency, secondary hyperparathyroidism, age, and debility are confounding factors. When UFH poses a risk or its use is contraindicated, e.g., after development of heparin-induced thrombocytopenia, the use of direct thrombin inhibitors, regional citrate anticoagulation, citrate dialysate, and heparin-free dialysis may be appropriate. © 2010 Wiley Periodicals, Inc.
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              A single dose of dalteparin effectively prevents clotting during haemodialysis.

              A single bolus dose of LMW heparin at the start of haemodialysis effectively prevents clot formation in the dialyser and bubble trap. However, there are few studies on the appropriate dosage of LMW heparins in haemodialysis. Therefore we examined the relationship between the anticoagulant effect of dalteparin and clinical clotting during haemodialysis. We performed an open, prospective study on the effect of decreasing doses of dalteparin in 12 haemodialysis patients during a total of 84 sessions (4-4.5 h). The normally applied dose of dalteparin in each patient was reduced by 25% for each session down to 50% of initial dose if no clotting was observed. Clinical clotting (grade 1-4) was evaluated by visual inspection after blood draining of the air trap every hour and by inspection of the dialyser after each session and compared to corresponding values for anti-FXa activity and dialysis time. Blood flow and ultrafiltration rate were kept within narrow limits throughout the study. No episodes of grade 4 clotting occurred, and no session was interrupted. Eighteen episodes of grade 3 clinical clotting (11%) were observed in patients without warfarin treatment, none with an anti-FXa activity >0.43 IU/ml. Oral warfarin treatment reduced the clinical clotting, and only one grade 3 episode was observed in patients on warfarin therapy. Anti-FXa activity and haemodialysis time were the only factors independently correlated to clotting in a logistic regression model. An anti-FXa activity above 0.4 IU/ml after 4 h of dialysis inhibits significant clotting during haemodialysis. A bolus dose of dalteparin of 70 IU/kg usually seems appropriate, but may be reduced in patients on warfarin treatment. Dialysis time is an independent risk factor for clinical clotting.
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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2012
                April 2013
                21 March 2013
                : 122
                : 1-2
                : 53-57
                Affiliations
                Renal Unit, Lister Hospital, Stevenage, UK
                Author notes
                *Sivakumar Sridharan, Renal Unit, Lister Hospital, Corey's Mill Lane, Stevenage, SG1 4AB (UK), E-Mail sridharansivakumar@gmail.com
                Article
                348830 Nephron Clin Pract 2012;122:53-57
                10.1159/000348830
                23548465
                3702f094-262b-46d7-aa41-2ad48df51b97
                © 2013 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
                : 20 August 2012
                : 15 January 2013
                Page count
                Figures: 4, Tables: 3, Pages: 5
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Anticoagulation,Haemodiafiltration,Haemodialysis,Dalteparin
                Cardiovascular Medicine, Nephrology
                Anticoagulation, Haemodiafiltration, Haemodialysis, Dalteparin

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