Clinical Investigation

Kidney International (1988) 33, 890–896; doi:10.1038/ki.1988.81

Comparison of low molecular weight heparin to standard heparin in hemodialysis/hemofiltration

Joachim Schrader1, Werner Stibbe1, Victor W Armstrong1, Michael Kandt1, Rainer Muche1, Heinz Köstering1, Dietrich Seidel1 and Fritz Scheler1

1Departments of Nephrology and Clinical Chemistry, Centre of Internal Medicine, University Clinic, Robert-Koch-Str. 40, D-3400 Göttingen, Federal Republic of Germany

Correspondence: Dr Joachim Schrader, Medizinische Klinik Goettingen, Abt. für Nephrologie, Robert-Koch-Strasse 40, D-3400 Goettingen, Federal Republic of Germany.

Received 27 May 1987; Revised 6 November 1987.

Top

Abstract

Comparison of low molecular weight heparin to standard heparin in hemodialysis/hemofiltration. Low molecular weight (LMW) heparin has been compared to standard unfractionated (UF) heparin in hemodialysis/hemofiltration in a 12 month, randomized study. Seventy patients with end-stage chronic renal failure starting dialysis treatment were randomly assigned to one of two groups treated with either LMW or UF heparin. The LMW and UF heparin doses used produced similar plasma anti-FXa levels, and comparable antithrombotic effectiveness was observed in the two groups as reflected in similar incidences of thrombus formation in the extracorporeal circulation: 1.59% and 1.33% for LMW and UF heparin, respectively. No bleeding complications were seen with either heparin, but significantly (P < 0.05) fewer erythryocyte concentrates were needed in the LMW heparin patients. Mean factor VIII activities had risen significantly (P < 0.001) after 12 months in the UF heparin group, whereas they were unchanged in the LMW heparin group. A significant (P < 0.05) increase in plasma triglycerides was observed in the UF heparin group which was attributable to six (18.8%) of the patients in this group. Triglyceride concentrations remained relatively constant in the LMW heparin group. Post-heparin lipolytic activity, and in particular hepatic lipase activity, was not stimulated to the same extent in the LMW heparin-treated patients as compared to the UF heparin group. We conclude that LMW heparin is a suitable alternative to standard UF heparin for anticoagulation in hemodialysis/hemofiltration therapy. It may offer potential advantages with regard to a lower requirement for erythrocyte concentrates and less derangement of certain metabolic parameters, such as factor VIII, triglycerides and plasma lipase activity.

Top

References

  1. Koch KM, Bechstein PB, Fassbinder W, Kaltwasser P, Schoeppe W: Occult blood loss and iron balance in chronic renal failure. Proc EDTA 12:681–684, 1975
  2. Larsson SO: On coagulation and fibrinolysis in uraemic patients on maintenance haemodialysis. Acta Med Scand 189:453–462, 1971
  3. Turney JH, Woods HF, Frewell MR, Weston MJ: Factor VIII complex in uremia and effects on hemodialysis. Br Med J 282:1653–1656, 1981
  4. Wessel-Aas T, Blomhoff JP, Wirum E, Nilson T: Hemodialysis and cell toxicity in vitro related to plasma triglycerides, post-heparin lipolytic activity and free fatty acids. Acta Med Scand 216:75–83, 1984
  5. Avioli LV: Heparin-induced osteoperia: An appraisal. Adv Exp Med Biol 52:375–379, 1975
  6. Crawford GA, Savdie E, Stewart JH: Heparin-released plasma lipases in chronic renal failure and after renal transplantation. Clin Sci 57:155–165, 1979 | PubMed | ISI | ChemPort |
  7. Salzman EW: Low-molecular-weight heparin: Is small beautiful? N Engl J Med 315:957–959, 1986
  8. Holmer E: Anticoagulant properties of heparin and heparin fractions. Scand J Haematol (Suppl) 25:25–39, 1980
  9. Kakkar VV, Djazaeri B, Fok J, Flechter M, Scully MF, Westwick J: Low-molecular-weight heparin and prevention of postoperative deep vein thrombosis. Br Med J 284:375–379, 1982
  10. Schrader J, Valentin R, Tönnis JH, Hildebrand U, Stibbe W, Armstrong VW, Kandt M, Köstering H, Quellhorst E: Low molecular weight heparin in hemodialysis and hemofiltration patients. Kidney Int 28:823–829, 1985
  11. Holmer E, Mattson C, Nilsson S: Anticoagulant and antithrombotic effects of heparin and low molecular weight heparin fragments in rabbits. Thromb Res 25:475–485, 1982
  12. Carter CJ, Kelton JG, Hirsh J, Cerskus A, Santos AV, Gent M: The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits. Blood 59:1239–1245, 1982 | PubMed | ChemPort |
  13. Cade JF, Buchanan MR, Boneu B, Ockelford P, Carter CJ, Cerskus AL, Hirsh J: A comparison of the antithrombotic and haemorrhagic effects of low molecular weight heparin fractions: The influence of the method of preparation. Thromb Res 35:613–625, 1984
  14. Hirsh J: Heparin induced bleeding. Nouv Rev Fr Haematol 26:261–264, 1984
  15. Hirsh J: In vivo effects of low molecular weight heparins on experimental thrombosis and bleeding. Haemostasis 16:82–86, 1986
  16. Persson E, Nordenström J, Nilsson-Ehle P, Hagenfeldt L: Lipolytic and anticoagulant activities of a low molecular weight fragment of heparin. Eur J Clin Invest 15:215–220, 1985
  17. Schrader J, Kandt M, Züchner C, Köstering H, Scheler F: Comparison of unfractionated heparin and low molecular weight heparin during long-term use in chronic haemodialysis and hemofiltration patients. Haemostasis 16(Suppl 2):48–58, 1986
  18. Teien AN, Lie M, Abilgaard U: Assay of heaprin in plasma using a chromogenic substrate for activated factor X. Thromb Res 8:413–416, 1976
  19. Lipinski B, Worowski K: Detection of soluble fibrin monomer complexes by means of protamine-sulfate-test. Thromb Diathes Haemorrh 20:44–49, 1968
  20. Friberger P: Chromogenic peptide substrates. Scand J Clin Lab Invest 42 (Suppl 162) 1–298, 1982
  21. Krauss RM, Lew y RI, Fredrickson DS: Selective measurement of two lipase activities in postheparin plasma from normal subjects and patients with hyperlipoproteinemia. J Clin Invest 54:1107–1124, 1974 | PubMed | ISI | ChemPort |
  22. Bolzano K, Krempler F, Sandhofer F: Hepatic and extrahe-patic triglyceride lipase activity in post-heparin plasma of normals and patients with cirrhosis of the liver. Horm Metab Res 7:238–241, 1975
  23. Lane DA, Flynn A, Ireland H, Anastassiades E, Curtis JR: On the evaluation of heparin and low molecular weight heparin in haemodialysis for chronic renal failure. Haemostasis 16 (Suppl 2):38–47, 1986
  24. Ockelford PA, Carter CJ, Mitchell L, Hirsh J: Discordance between the anti-Xa-activity and the antithrombotic activity of an ultra-low-molecular-weight heparin fraction. Thrombin Res 28:401–409, 1982
  25. Turney JH, Fewell M, Williams LC, Dodd N, Weston MJ: Paradoxial behaviour of antithrombin III during hemodialysis and its prevention with prostacyclin. Clin Nephrol 17:31–35, 1982
  26. Zahorsky R, Proppe D, Wronski R, Loose G, Thomas R, Niedermayer W: Niedermolekulares (NM) Heparin im Vergleich mit unfraktioniertem Heparin auf den chronischen Blutverlust bei Hämodialysepatienten. Nieren- und Hochdruckkrankheiten 15:402, 1986
  27. Salzman EW, Rosenberg RD, Smith MH, Lindon JN, Favreau L: Effect of heparin and heparin fractions on platelet aggregation. J Clin Invest 65:64–73, 1980
  28. Holmer E, Lindahl U, Backström G, Thumberg L, Sandberg H, Söderström G, Andersson L-O: Anticoagulant activities and effects on platelets of a heparin fragment with high affinity for antithrombin. Thromb Res 18:861–869, 1980
  29. Borm JJJ, Kredict R, Sturk A, TenCate JW: Heparin versus low molecular weight heparin K 2165 in chronic hemodialysis patients: A randomized cross-over study. Haemostasis 16 (Suppl 2):59–68, 1986
  30. Barzu T, Moklo P, Tobelem G, Petitou M, Caen JP: Binding of heparin and low molecular weight heparin fragments to human vascular endothelial cells in culture. Nouv Rev Fr Hematol 26:243–247, 1984
  31. Huttunen JK, Pasternack A, Vänttinen T, Ehnholm C, Nikkilä EA: Lipoprotein metabolism in patients with chronic uremia. Acta Med Scand 204:211–218, 1978
  32. Chan MK, Varghese Z, Moorhead JF: Lipid abnormalities in uremia, dialysis and transplantation. Kidney Int 19:625–637, 1981 | PubMed | ISI | ChemPort |
  33. Nestel PJ, Fidge NH, Tan MH: Increased lipoprotein remnant formation in chronic renal failure. N Engl J Med 307:329–333, 1982 | PubMed | ISI | ChemPort |
  34. Murase T, Cattran DC, Rubenstein B, Steiner G: Inhibition of lipoprotein lipase by uraemic plasma: A possible cause of hypertriglyceridemia. Metabolism 24:1279–1286, 1975
  35. Ibels LS, Reardon MF, Nestel PJ: Plasma post-heparin lipolytic activity and triglyceride clearance in uremic and hemodialysis patients and renal allograft recipients. J Lab Clin Med 87:648–658, 1976 | PubMed | ISI | ChemPort |
  36. Stibbe W, Walli AK, Schrader J, Seidel D: Differences in lipolytic activities of a low molecular weight heparin and of unfractionated heparin in haemodialysis patients, in Drugs Affecting Lipid Metabolism, Florenz, 1986, p. 77
  37. Lindner A, Chara B, Sherrard DJ, Scribner BH: Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 290:697–701, 1974 | PubMed | ISI | ChemPort |
  38. Lowrie EG, Lazarus JM, Hampers CL, Merrill JP: Cardiovascular disease in hemodialysis patients. N Engl J Med 290:737–738, 1974 | PubMed | ISI | ChemPort |
  39. Green D, Stone NJ, Krumlovsky FA: Putative atherogenic factors in patients with chronic renal failure. Prog Cardiovasc Dis 26:133–144, 1983 | PubMed | ISI | ChemPort |

Extra navigation

.
ADVERTISEMENT