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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Effects of Epoetin Alfa on Hemostasis in Chronic Renal Failure

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          Abstract

          Epoetin alfa is the cornerstone of anemia therapy in patients with end-stage renal disease. In addition to stimulating erythropoiesis, Epoetin alfa has been demonstrated to affect hemostasis. Such effects may be important because patients with chronic renal failure have a bleeding diathesis that is multifactorial in origin. Therefore, a computer literature search on the relationship between Epoetin alfa therapy for anemia in patients with end-stage renal disease and platelets, coagulation, coagulation inhibitors, and fibrinolysis was performed. All articles and abstracts reporting original data in the English language on Epoetin alfa and its effect on hemostasis were reviewed. The literature suggests that the effects of Epoetin alfa on the coagulation cascade are of minimal clinical importance. However, Epoetin alfa transiently increases the number of circulating platelets and improves platelet function, and these effects are associated with a return of the bleeding time towards normal.

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          Hemostasis in renal disease: pathophysiology and management.

          The hemostatic abnormalities commonly encountered in patients with renal disease can significantly threaten the well-being of the patient and pose difficult management issues for the clinician. In this review, we explore the pathophysiology underlying the bleeding diathesis and hypercoagulability that can occur. Current therapeutic interventions are also discussed.
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            A study of platelet functions, some hemostatic and fibrinolytic parameters in relation to serotonin in hemodialyzed patients under erythropoietin therapy.

            Erythropoietin corrects anemia and improves hemostasis, but on the other hand bears a risk of thrombotic complications. Therefore in the present study an attempt has been made to evaluate bleeding time, platelet functions and some hemostatic and fibrinolytic parameters in relation to blood and platelet serotonin before and after 1, 2, 4, 8 and 12 weeks of treatment. 22 chronically hemodialyzed patients were administered with human recombinant erythropoietin (rHuEPO) in a dose of 2000 IU s.c. 3 times a week. Bleeding time was shortened significantly as early as after 1 week of the therapy, whereas hematocrit and hemoglobin increased after 2 weeks. These changes lasted throughout the study. Only a transient rise in platelet count, collagen-induced platelet aggregation, beta-thromboglobulin and VIII:C activity were observed during therapy relative to baseline values. ADP- and arachidonic acid-induced platelet aggregation seemed to be unaffected by rHuEPO treatment, whereas a gradual and progressive enhancement in platelet aggregation in response to ristocetin was found, starting from the 2nd week of the therapy. It lasted throughout the study and correlated inversely with the bleeding time and positively with a rise in both blood and platelet serotonin. rHuEPO did not alter plasminogen, fibrinogen, platelet factor 4, alpha 2 macroglobulin levels, protein C activity and euglobulin clot lysis time. A decline in protein C and S concentrations and antithrombin III activity observed during the therapy were counterbalanced by a fall in the activity of alpha 2 antiplasmin, C1 esterase inhibitor and plasminogen activator inhibitor. It is concluded that rHuEPO may improve platelet/vessel wall interactions possibly by means of serotonergic mechanisms. A lowered activity of inhibitors of fibrinolysis may be regarded as a protection against a general tendency to thrombosis during rHuEPO therapy.
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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
              1998
              August 1998
              05 June 1998
              : 18
              : 4
              : 263-273
              Affiliations
              Department of Clinical Research, Amgen Inc., Thousand Oaks, Calif., USA
              Article
              13349 Am J Nephrol 1998;18:263–273
              10.1159/000013349
              9653828
              98f4a87a-c367-4f39-8818-96f1ed34c5d0
              © 1998 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
              Page count
              Tables: 5, References: 56, Pages: 11
              Categories
              Editorial Review

              Cardiovascular Medicine,Nephrology
              Antithrombin III,Coagulation,Dialysis,End-stage renal disease,Epoetin alfa,Fibrinolysis,Platelets,Protein C,Protein S

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