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      Comparison of Tinzaparin™ and Unfractionated Heparin as Anticoagulation on Haemodialysis: Equal Safety, Efficacy and Economical Parity

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          Abstract

          Background: The European Best Practice Guidelines on anticoagulation in chronic haemodialysis recommend the use of low-molecular-weight heparins (LMWH) over unfractionated heparin (UFH), based on previous small-scale studies and a meta-analysis which demonstrated equal efficacy of anticoagulation without an increase in hemorrhagic events. Method: We performed a prospective single-centre study where all stable patients on chronic in-hospital haemodialysis were converted from UFH to Tinzaparin™. Patients were monitored for 2 months before and 2 months after the switch. Access failures due to thrombosis, clotted circuits and hemorrhagic events were recorded. Results: 1,489 and 1,823 dialysis sessions took place on UFH and LMWH, respectively, in 108 patients (65 male). The total number of clotted circuits tended to decrease after the switch to LMWH (34 vs. 13) but was not statistically significant. There were four minor non-access-related episodes of haemorrhage while on treatment with UFH and none with Tinzaparin, and the length of bleeding time post needle removal was shorter with Tinzaparin than UFH. The cost-analysis demonstrated parity of Tinzaparin with UFH; using a median of 10,000 U of UFH versus 2,500 U of LMWH, each therapy cost GBP 10,783 (EUR 15,942; USD 20,446) per annum. Conclusion: Our findings suggest comparable safety and efficacy of Tinzaparin, parity of cost in comparison with UFH.

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          Most cited references25

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          Safety and efficacy of low molecular weight heparins for hemodialysis in patients with end-stage renal failure: a meta-analysis of randomized trials.

          Low molecular weight heparins (LWMH) are the preferred initial treatment for many thromboembolic disorders but are renally excreted and relatively contraindicated in patients with renal failure because of concerns of increased bleeding risks. The purpose of this study was to evaluate the safety and efficacy of LMWH compared with unfractionated heparin (UFH) for preventing thrombosis of the extracorporeal dialysis circuit. Studies were identified with the use of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and FirstSearch; reference lists were reviewed; and pharmaceutical companies were contacted. Randomized, controlled trials that compared an LMWH with another anticoagulant during hemodialysis in patients with ESRD and reported at least one of bleeding, extracorporeal circuit thrombosis, or anti-Xa levels were chosen. Two reviewers independently extracted data on methodologic quality, study design, clinical outcomes, and anti-Xa levels. Seventeen trials were included in this systematic review, 11 of which were included in the meta-analysis. It was found that LMWH did not significantly affect the number of bleeding events (relative risk, 0.96; 95% confidence interval [CI], 0.27 to 3.43), bleeding assessed by vascular access compression time (weighted mean difference, -0.87; 95% CI, -2.75 to 1.02), or extracorporeal circuit thrombosis (relative risk, 1.15; 95% CI, 0.70 to 1.91) as compared with UFH. LMWH seem to be as safe as UFH in terms of bleeding complications and as effective as UFH in preventing extracorporeal circuit thrombosis. However, inferences from these trials assessing anticoagulation for patients who undergo hemodialysis will continue to be weak until larger, more rigorous randomized trials are conducted.
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            Development of platelet contractile force as a research and clinical measure of platelet function.

            David Carr (2002)
            This article reviews work performed at the Medical College of Virginia of Virginia Commonwealth University during the development of a whole-blood assay of platelet function. The new assay is capable of assessing platelet function during clotting and thus allows measurement of the contribution of platelets to thrombin generation. Because platelets are monitored in the presence of thrombin, the test gages platelets under conditions of maximal activation. Three parameters are simultaneously assessed on one 700 microL sample of citrated whole blood. Platelet contractile force (PCF), the force produced by platelets during clot retraction, is directly measured as a function of time. This parameter is sensitive to platelet number, platelet metabolic status, glycoprotein IIb/IIIa status, and the presence of antithrombin activities. Clot elastic modulus (CEM), also measured as a function of time, is sensitive to fibrinogen concentration, platelet concentration, the rate of thrombin generation, the flexibility of red cells, and the production of force by platelets. The third parameter, the thrombin generation time (TGT) is determined from the PCF kinetics curve. Because PCF is absolutely thrombin dependent (no thrombin-no force), the initial upswing in PCF occurs at the moment of thrombin production. TGT is sensitive to clotting factor deficiencies, clotting factor inhibitors, and the presence of antithrombins, all of which prolong the TGT and are known to be hemophilic states. Treatment of hemophilic states with hemostatic agents shortens the TGT toward normal. TGT has been demonstrated to be shorter and PCF to be increased in coronary artery disease, diabetes mellitus, and several other thrombophilic states. Treatment of thrombophilic states with a variety of heparin and nonheparin anticoagulants prolongs the TGT toward normal. The combination of PCF, CEM, and TGT measured on the same sample may allow rapid assessment of global hemostasis and the response to a variety of procoagulant and anticoagulant medications.
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              Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency.

              To compare the frequency of bleeding complications from enoxaparin in patients with normal renal function versus patients with renal insufficiency. Retrospective chart review. University-based tertiary care center. One hundred six patients who received two or more doses of enoxaparin. Total bleeding complications occurred in 22% of patients with normal renal function and 51% with renal insufficiency (p<0.01). Major bleeds were also significantly different, 2% and 30%, respectively (p<0.001). No patients with normal renal function were given fresh-frozen plasma or packed red blood cells, whereas in those with renal insufficiency, 13% and 32%, respectively, received these products (p<0.01). Enoxaparin may have resulted in increased bleeding complications and use of blood products in patients with renal insufficiency. Prospective studies need to be conducted to define the drug's role and dosage adjustments in these patients.
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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
                2008
                November 2008
                30 September 2008
                : 110
                : 2
                : c107-c113
                Affiliations
                South West Thames Renal Unit, St Helier Hospital, London, UK
                Article
                158561 Nephron Clin Pract 2008;110:c107
                10.1159/000158561
                18824874
                121b8b1d-1ab6-4e80-ac70-f92b31766e0a
                © 2008 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 April 2007
                : 24 June 2008
                Page count
                Tables: 4, References: 44, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Low-molecular-weight heparin,Anticoagulation,Haemodialysis
                Cardiovascular Medicine, Nephrology
                Low-molecular-weight heparin, Anticoagulation, Haemodialysis

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