Background: To compare standard heparin (SH) and low molecular weight heparin (LMWH) in terms of anticoagulation, platelet activation and lipid metabolism, we selected 54 patients who had been on 4-hour hemodialysis three times weekly for at least 12 months, without bleeding disorders or dyslipidemic diseases. 28 were on hemodialysis with Polysulfone low-flux, 26 were on hemodiafiltration with Polysulfone high-flux. All patients underwent EPO. Methods: During the first 18 months, we administered SH 1,500 IU on starting dialysis and 1,500 ± 500 IU in continuous intradialytic infusion per session. In the following 18 months, we administered LMWH 64.6 IU/kg on starting dialysis in a single arterious bolus. We assessed aPTT, anti-factor Xa activity, TAT and FPA, β-TG and PF4. Blood samples were taken monthly at times 0, 30, 60, 180 and 240 min, as well as 1, 4 and 20 h after dialysis end. Predialysis cholesterol, HDL, LDL, triglycerides and lipoprotein(a) were checked monthly. Results: During both LMWH and SH sessions no clotting or major bleeding complications were observed. APTT with LMWH was lower than that found with SH (p < 0.001); aFXa using LMWH was higher than when using SH (p < 0.001); TAT and FPA were lower in LMWH sessions (p < 0.01) than in SH sessions. We also detected lower β-TG (p < 0.05) and PF4 levels (p < 0.05) using LMWH than using SH. As regards lipids, we only observed a significant decrease in triglycerides after 18 months of LMWH treatment. Conclusions: Routine use of LMWH during hemodialysis affords a safe and effective alternative to SH, and causes reduced platelet activation.

Keywords:
Anticoagulation, Low-molecular-weight heparin, Lipid metabolism, Platelet activation, Standard heparin
1.
Lindsay RM, Mason RG, Kim SW, Andrade JD, Hakim RM: Panel conference: Blood surface interactions. Trans Am Soc Artif Intern Organs 1980;26:603–610.
2.
Buscaroli A, Colì L, Cianciolo G, Grossi G, Bonetti M, Nanni Costa A, Borgnino LC, Stefoni S, Bonomini V: Biocompatibility of artificial membranes: Platelet function evaluation. Biocyber Biomed Eng 1991;11:5–12.
3.
Notohamiprodjo M, Andrassy K, Bommer J, Ritz E: Dialysis membranes and coagulation system. Blood Purif 1986;4:130–141.
4.
Von Sengbusch G: Membranes in dialysis – performance and hemocompatibility; in Falkenagen D, Klinkmann H, Piskin E, Opätrny K (eds): Blood-Material Interaction: A Basic Guide from Polymer Science to Clinical Application. Glasgow, INFA, 1998, pp 79–89.
5.
Sagripanti A, Cupisti A, Baicchi U, Federghini, Morelli E, Barsotti G: Plasma parameters of the prothombotic state in chronic uremia. Nephron 1993:63:273–278.
6.
Lai KN: Protein C, protein S, and antithrombin III metabolism in dialysis patients. Int J Artif Organs 1993;16:4–6.
7.
Callander N, Rapaport SI: Trousseau’s syndrome. West J Med 1993;158:364–371.
8.
Opatrny K, Opatrna S, Vit L, Opatrny K, Blaha J, Valek A: Plasma concentrations of the thrombin-antithrombin III complex in dialysis patients during erythropoietin therapy. Nephrol Dial Transplant 1992;7:1072–1073.
9.
Engbers G, Feijen J: Current techniques to improve the blood compatibility of biomaterials surfaces. Int J Artif Organs 1991;14:199–215.
10.
Lin JY, Okano T, Dost L, Feijen J, Kim SW: Prevention of platelet contact activation by prostaglandin E1 released from polyurethane surfaces. Trans Am Soc Artif Intern Organs 1985;31:468–473.
11.
Hory B, Saint-Hillier Y, Perol JC: Prostacyclin as the sole antithrombotic agent for acute renal failure hemodialysis. Nephron 1983;33:71.
12.
Janssen MJ, Deegens JK, Kapinga TH, Beukhof JR, Hujgens PC, van Loenen AC, van der Meulen J: Citrate compared to low molecular weight heparin anticoagulation in chronic hemodialysis patients. Kidney Int 1996;49:806–813.
13.
Maurin N, Ballmann M: Prevention of coagulation during hemodialysis by a combination of the stable prostacyclin analogue CG 4203 and low-dose heparin. Clin Nephrol 1988;5:125–130.
14.
Ouseph R, Ward RA: Anticoagulation for intermittent hemodialysis. Semin Dialysis 2000;13:181–187.
15.
Stiekema JCJ: Heparin and its biocompatibility. Clin Nephrol 1986;26:3–8.
16.
Hofbauer R, Moser D, Frass M, Oberbauer R, Kaye A, Wagner O, Kapiotis S, Druml W: Effect of anticoagulation on blood membrane interactions during hemodialysis. Kidney Int 1999;56:1578–1583.
17.
Goudable C, Saivin S, Houin G, Sie P, Boneu B, Tonthat H, Suc JM: Pharmacokinetics of a low molecular weight heparin (Fraxiparine) in various stages of chronic renal failure. Nephron 1991;59:543–545.
18.
Holmer E, Kurachi K, Sönderström G: The molecular-weight dependence of the rate-enhancing effect of heparin on the inhibition of thrombin, factor Xa, factor IXa, factor XIa, factor XIIa and kallikrein by antithrombin. Biochem J 1981;193:395–400.
19.
Schrader J, Stibbe W, Armstrong VW, Kandt M, Muche R, Kostering H, Seidel D, Scheler F: Comparison of low molecular weight heparin vs. standard heparin in hemodialysis/hemofiltration. Kidney Int 1988;33:890–896.
20.
Lai KN, Wang AYM, Ho K, Szeto CC, Li M, Wong, LKS, Yu AWY: Use of low-dose low molecular weight heparin in hemodialysis. Am J Kidney Dis 1996;28:721–726.
21.
Finazzi G, Remuzzi G: Heparin-induced thrombocytopenia – background and implications for haemodialysis. Nephrol Dial Transplant 1996;11:2120–2122.
22.
Aster RH: Heparin-induced thrombocytopenia and thrombosis. N Engl J Med 1995;332:1374–1376.
23.
Bartelè V, Roncaglioni MC, Donati MB, De Gaetano G: Heparin counteracts the antiaggregating effect of prostacyclin by potentiating platelet aggregation. Thromb Haemostas 1983;49:81–83.
24.
Ward RA: Effects of haemodialysis on coagulation and platelets: are we measuring membrane biocompatibility? Nephrol Dial Transplant 1995;10(suppl 10):12–17.
25.
Stenvinkel P: Low molecular weight heparin – does it favourably affect lipid levels? Nephrol Dial Transplant 1995;10:16–18.
26.
Ishii Y, Yano K, Kanai I, Maezawa I, Tsuchida I, Wakamatsu R, Naruse T: Evaluation of the blood coagulation-fibrinolysis system in patients receiving chronic hemodialysis. Nephron 1996;73:407–412.
27.
Wilhelmsson S, Asaba S, Gunnarsson B, Kudryk B, Robinson D, Bergström J: Measurement of fibrinopeptide A in the evaluation of heparin activity and fibrin formation during haemodialysis. Clin Nephrol 1981;15:252–258.
28.
Simpson HKL, Baird J, Allison M, Briggs JD, Rowe PA, Welsh M, Macdougall AI, Grant AC, Lowe GDO, Runley A, Wallace M, Menday AP: Long-term use of low molecular weight heparin tinzaparin in haemodialysis. Haemostasis 1996;26:90–97.
29.
Reach I, Luong N, Chastang C, Chakroun M, Mirshahi S., Mirsahahi MC, Soria J, Desmichelis D, Baumelou A: Dose effect relationship of reviparin in chronic hemodialysis: A crossover study vs. nadroparin. Artificial Organs 2001;27:591–595.
30.
Ljunberg B, Jacobson SH, Lins LE, Pejler G: Effective anticoagulation by a low molecular weight heparin (fragmin) in haemodialysis with a highly permeable polysulfone membrane. Clin Nephrol 1992;38:97–100.
31.
Sagedal S, Hartmann A, Sundstrøm K, Bjørnsen S, Fauchald P, Brosstad F: A single dose of deltaparin effectively prevents clotting during haemodialysis. Nephrol Dial Transplant 1999;14:1943–1947.
32.
Saltissi D, Morgan C, Westhuyzen J, Healy H: Comparison of low-molecular-weight heparin (enoxaparin sodium) and standard unfractioned heparin for haemodialysis anticoagulation. Nephrol Dial Transplant 1999;14:2698–2703.
33.
Nurmohamed MT, ten Cate J, Stevens P, Hoek JA, Lins RL, ten Cate JW: Long term efficacy and safety of a low molecular weight heparin in chronic hemodialysis patients. ASAIO Trans 1991;37:M459–461.
34.
Leu JG, Chiang SS, Lin SM, Pai JK, Jiang WW: Low molecular weight heparin in hemodialysis patients with a bleeding tendency. Nephron 2000;86:499–501.
35.
Mohr R, Golan M, Martinowitz U, Rosner E, Goor DA, Ramot B: Effect of cardiac operation on platelets. J Thoracic Cardiovasc Surg 1986;92:434–441.
36.
Remuzzi G: Bleeding disorders in uremia: Pathophysiology and treatment. Adv Nephrol 1989:18:171–186.
37.
Matsuda T: Biological responses at non-physiological interfaces and molecular design of biocompatible surfaces. Nephrol Dial Transplant 1989;4(suppl 3):60–66.
38.
Cianciolo G, Stefoni S, Donati G, De Pascalis A, Iannelli S, Manna C, Colì L, Bertuzzi V, La Manna G, Raimondi C, Boni P, Stefoni V: Intra- and postdialytic platelet activation and PDGF-AB release: Cellulose diacetate vs. polysulfone membranes. Nephrol Dial Transplant 2001;16:1222–1229.
39.
Sueishi K, Ichikawa K, Kato K, Nakagawa K, Chen Y: Atherosclerosis: Coagulation and fibrinolysis. Semin Thromb Hemost 1998;24:255–260.
40.
Elisaf MS, Germanos NP, Bairaktari HT, Pappas MB, Koulouroudis EI, Siamopoulos KC: Effects of conventional vs. low-molecular-weight heparin on lipid profile in hemodialysis patients. Am J Nephrol 1997;17:153–157.
41.
Liu G, Hultin M, Ostergaard P, Olivecrona T: Interaction of size-fractioned heparins with lipoprotein lipase and hepatic lipase in the rat. Biochem J 1992;285:731–736.
42.
Williams KJ, Petrie KA, Brocia RM, Swenson TL: Lipoprotein lipase modulates net secretory output of apolipoprotein B in vitro. J Clin Invest 1991;88:1300–1306.
43.
Schmitt Y, Schenider H: The application of low molecular weight heparin during dialysis in chronic hemodialysis patients and its influence on lipoprotein metabolism; in Gotto AM Jr, Mancini M, Richter WO, Swandt P (eds): Treatment of Severe Dyslipoproteinemia in the Prevention of Coronary Heart Disease. 3rd Int Symp, Munich 1990. Basel, Karger, 1992, pp 314–318.
44.
Kronenberg F, König P, Lhotta K, Steinmetz A, Dieplinger H: Low molecular weight heparin does not necessarily reduce lipids and lipoproteins in hemodialysis patients. Clin Nephrol 1995;43:399–404.
45.
Kronenberg F, König P, Neyer U, Auinger M, Pribasnig A, Meisl T, Pinter G, Dieplinger H: Influence of various heparin preparations on lipoproteins in hemodialysis patients: A multicentre study. Thromb Haemost 1995;74:1025–1028.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.