Abstract
A tendency toward thrombosis (particularly of the arterovenous shunt) is a frequent complication of uremic patients on hemodialysis. It is well known that uremia is associated with complex coagulation abnormalities (1–4) which include both bleeding diathesis (for a review see chapter by Winchester JF) and hypercoagulability. Table 1 shows the factors involved in the latter disturbance. The results of the global coagulation screening tests in uremic patients are generally normal. Most consistent findings are an increased level of fibrinogen (5) and decreased protein C anticoagulant activity with normal amidolytic activity and antigen (6, 7). Recently, it has been documented that the reduced protein C anticoagulant activity is due to the presence of a soluble plasma inhibitor that interferes specifically with the anticoagulant activity of activated protein C (8). Given the role of fibrinogen and protein C in coagulation homeostasis, it is not surprising that these abnormalities contribute to the increased risk of thrombosis episodes in these patients. In vivo studies have also demonstrated enhanced platelet activity in this population (9–11).
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References
Remuzzi G: Bleeding in renal failure. Lancet 1: 1205, 1988
Llach F: Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 28: 429, 1985
Hocking WG: Hematologic abnormalities in patients with renal disease. Hematol Oncol ClinNorth Am 1: 229, 1987
Viganò G, Remuzzi G: Disorders of hemostasis in dialysis patients, in The Principles and Practice of Dialysis, edited by Henrich WL, Baltimore, Williams & Wilkins, 1994, p 287
Koppensteiner R, Stockenhuber F, Derfler K et al.: Fibrinogen in kidney disease, in Fibrinogen: A New Cardiovascular Risk Factor, edited by Ernest E, Koening W, Lowe GDO, Meade TW, Wien, Blackwell-MZV, 1992, p 301
Sorensen PJ, Knudsen F, Nielsen AH et al.: Protein C assay in uremia. Thromb Res 301, 1989
Sorensen PJ, Nielsen AH, Knudsen E, Dyerberg J: Defective protein C in uremia. Blood Purif 5: 29, 1987
Faioni EM, Franchi F, Krachmalnicoff A et al.: Lowlevels of the anticoagulant activity of Protein C in patients with chronic renal insufficiency: an inhibitor of Protein C is present in uremic plasma. Thromb Haemostas 66: 420, 1991
Viener A, Aviram M, Better OS, Brook JG: Enhanced in vitro platelet aggregation in hemodialysis patients. Nephron 43: 139, 1986
Lindsay RM, Prentice CRM, Davidson JF et al.: Haemostatic changes during dialysis associated with thrombus formation on dialysis membranes. Br Med J 4: 454, 1972
George CPR, Slichter SJ, Quadracci LJ et al.: A kinetic evaluation of hemostasis in renal disease. N Engl J Med 293: 1111, 1974
Smith MC, Dunn MJ: Impaired platelet thromboxane production in renal failure. Nephron 29: 133, 1981
Jorgenson KA, Ingeborg S: Platelets and platelet function in patients with chronic uremia on maintenance hemodialysis. Nephron 23: 233, 1979
Nenci GG, Berrettini M, Agnelli G et al.: Effects of peritonela dialysis, hemodialysis and kidney transplantation on blood platelet function. Nephron 23: 287, 1979
Lindsay RM, Moorthy AV, Koens F, Linton AL: Platelet function in dialyzed and non-dialyzed patients with chronic renal failure. Clin Nephrol 4: 52, 1975
Bemis J, Rigney J, Sosin A, Deane N: Enhanced platelet aggregation in chronic renal failure patients receiveing hemodialysis treatment. Trans Am Soc Artif Intern Organs 23: 48, 1977
Garcia-Martin F, De Arriba G, Carrascosa T et al.: Anti-cardiolipin antibodies and lupus anticoagulant in end-stage renal disease. Nephrol Dial Transplant 6: 543, 1991
Quereda C, Pardo A, Lamas S et al.: Lupus-like in vitro anticoagulant activity in end-stage renal disease. Nephron 49: 39, 1988
Freyssinet JM, Ravanat C, Grunebaum L et al.: Anti-phospholipid autoantibodies in thrombosis: cause and/or consequence of the disruption of the protein C-dependent hemostatic balance, in Phospholipid-binding Antibodies, edited by Harris EN, Exner T, Hughes GRV, Asherson TA, Boca Raton, CRC Press, 1991, p 255
Forbes CD, Prentice CRM: Thrombus formation and artificial surfaces. Br Med Bull 34: 201, 1978
Lindsay RM, Mason RG, Kim SW, Andrade JD, Hakim RM: Blood surface interactions — report of ASAIO panel conference. Trans Am Soc Artif Intern Organs 26: 603, 1980
Fan P, Schwab SJ: Hemodialysis vascular access, in The Principles and Practice of Dialysis, edited by Henrich WL, Williams & Wilkins, Baltimore, 1994, p 22
Galbraith S, Fan P, Collins D, Schawb S: Hemodialysis fistula thrombosis: a prospective evaluation of anatomic vs nonanatomic causes. J Am Soc Nephrol 3: 365, 1992
Feldman HI, Held PJ, Stoiber E et al.: Dialysis vascular access morbidity in the USA. J Am Soc Nephrol 1: 356, 1991
Del Greco F, Soper WS, Krumlovsky FA et al.: Thrombosis of vascular access for hemodialysis. in Haemostasis and the Kidney, edited by Remuzzi G, Rossi EC, Butterworths, London, 1989, p 303
Kirschbaum B, Mullinax F, Curry N, Mallory J: Association between anticardiolipin antibody and frequent clotting problems in hemodialysis patients. J Am Soc Nephrol 2: 232, 1991
Alegre A, Vicente V, Gonzales R, Alberca I: Effect of hemodialysis on Protein C. Nephron 46: 386, 1987
Lai KN, Yin JA, Yuen PMP, Li PKT: Effect of hemodialysis on protein C, protein S, and antithrombin III levels. Am J Kidney Dis 17: 38, 1991
Palder SB, Kirkman RL, Wittermore AD, Hakim RM, Lazarus JM, Tilney NL: Vascular access for hemodialysis. Ann Surg 202: 235, 1985
Zibari GB, Rohr MS, Landreneau MD et al.: Complications from permanent hemodialysis vascular access. Surgery 104:681, 1988
Raju S: PTFE grafts for hemodialysis access. Ann Surg 206: 666, 1987
Winearls CG, Pippard MJ, Dowing MR et al.: Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 2: 1175, 1986
Ad Hoc Committee for the National Kidney Foundation: Statement on the clinical use of recombinant erythropoietin in anemia of end-stage renal disease. Am J Kidney Dis 14: 163, 1989
Viganò G, Benigni A, Mendogni D, Mingardi G, Mecca G, Remuzzi G: Recombinant human erythropoietin to correct uremic bleeding. Am J Kidney Dis 18: 44, 1991
Eschbach JW: Erythropoietin 1991 — an overview. Am J Kidney Dis 18(Suppl I): 3, 1991
Eschbach JW, Adamson JW: Guidelines for recombinant human erythropoietin therapy. Am J Kidney Dis 14(Suppl 1): 2, 1989
Eschbach JW, Adamson JW: Recombinant human erythropoietin: implication for nephrology. Am J Kidney Dis 11:203, 1988
Taylor JE, Belch JJ, McLaren M, Henderson IS, Stewart WK: Effect of erythropoietin therapy and withdrawal on blood coagulation and fibrynolysis in hemodialysis patients. Kidney Int 44: 182, 1993
MacDougall IC, Davies ME, Hallett I, Cichlin DL, Hutton RD, Coles GA, Williams JD: Coagulation studies and fistula blood flow during erythropoietin therapy in haemodialysis patients. Nephrol Dial Transplant 6: 862, 1991
Muirhead N, Laupacis A, Wong C: Erythropoietin for anaemia in haemodialysis patients: results of a maintenance study. Nephrol Dial Transplant 7: 811, 1992
Shand BI, Buttimore AL, Hurrell MA et al.: Hemorheology and fistula function in home hemodialysis patients following erythropoietin treatment: a placebo-controlled study. Nephron 64: 53, 1993
Standage BA, Schuman ES, Ackerman D, Gross GF, Rangsdale JW: Does the use of erythropoietin in hemodialysis patients increase dialysis graft thrombosis rates? Am J Surg 165: 650, 1993
Zeit RM, Cope C: Failed hemodialysis shunts. Radiology 154: 353, 1985
Young AT, Hunter DW, Castaneda-Zuniga WP et al.: Thrombosed synthetic hemodialysis access fistulas: failure of thrombolytic therapy. Radiology 154: 639, 1985
Mangiarotti G, Canavese C, Thea A et al.: Urokinase treatment for arteriovenous fistulae declotting in dialyzed patients. Nephron 36: 60, 1984
Schilling JJ, Eiser AR, Slifkin RF, Withney JT, Neff MS: The role of thrombolysis in hemodialysis access occlusion. Am J Kidney Dis 10: 92, 1987
Rodkin RS, Bookstein JJ, Heeney DJ, Davis GB: Strep-tokinase and transluminal angioplasty in the treatment of acutelythrombosed hemodialysis access fistulas. Radiology 149: 425, 1983
Tordoir JHM, Herman JMMPH, Kwan TS, Diderich PM: Long-term follow-up of the polytetrafluoroethylene (PFTE) prosthesis as an arteriovenous fistula for haemodialysis. Eur J Vase Surg 2: 3, 1987
Brunner MC, Matalon TA, Patel SK, McDonald V, Jensik SC: Ultrarapid urokinase in hemodialysis access occlusion. J Vasc Intervent Radiol 2: 503, 1991
Valji K, Bookstein JJ, Roberts AC, Davis GB: Pharma-comechanical thrombolysis and angioplasty in the management of clotted hemodialysis grafts: early and late clinical results. Radiology 178: 243, 1991
Matuszkiewicz-Rowinska J, Billip T, Omecka Z, Rowinski W, Sicinski A: Systemic streptokinase infusion for declotting of hemodialysis arteriovenous fistulas. Nephron 66: 67, 1994
Ahmed A, Shapiro WB, Porush JG: The use of tissue plasminogen activator to declot arteriovenous accesses in hemodialysis patients. Am J Kidney Dis 21: 38, 1993
Sreedhara R, Himmelfarb J, Lazarus JM, Hakim RM: Antiplatelet therapy in expanded polytetrafluoroethylene (ePTFE) graft thrombosis: results of a randomized double-blind study. J Am Soc Nephrol 4: 388 (Abstract 9P), 1993
Michie DD, Wombolt DG: Use of sulfilnpyrazone to prevent thrombus formation in arteriovenous fistulas and bovine grafts of patients on chronic hemodialysis. Ther Res 22: 196, 1977
Kobayashi K, Maeda K, Koshikawa S et al.: Antithrombotic therapy with ticlopidine in chronic renal failure patients on maintenance hemodialysis — a multicenter collaborative double blind study. Thromb Res 20: 255, 1980
Domoto DT, Bauman JE, Joist JH: Combined aspirin sulfynpirazone in the prevention of recurrent hemodialysis vascular access thrombosis. Thromb Res 82: 737, 1991
Harter HR, Burch JW, Majerus PW et al.: Prevention of thrombosis in patients on hemodialysis by low dose aspirin. N Engl J Med 301: 577, 1979
Livio M, Benigni A, Viganò G, Mecca G, Remuzzi G: Moderate doses of aspirin and risk of bleeding in renal failure. Lancet 1: 414, 1986
Gaspari F, Viganò G, Orisio S, Bonati M, Livio M, Remuzzi G: Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition. J Clin invest 79: 1788, 1987
Steiner RW, Coggins C, Carvalho ACA: Bleeding time in uremia. Am J Hematol 7: 107, 1979
Viganò G, Remuzzi G: Low-dose aspirin and bleeding in uremia. Am J Hematol 42: 235, 1993
Antiplatelet Trialists’ Collaboration: Collaborative overview of randomized trials of antipylatelet therapy. II: Maintenance of vascular graft of arterial patency by antiplatelet therapy. Br Med J 308: 159, 1994
Sreedhara R, Himmelfarb J, Lazarus JM, Hakim RM: Antiplatelet therapy in graft thrombosis: results of a prospective, randomized double-blind study. Kidney Int 45: 1477, 1994
Tollefaen DM, Majerus DW, Blank MK: Heparin cofactor II. J Biol Chem 257: 2162, 1982
Salzman EW, Rosenberg RD, Smith MH, Lindon JN, Favreau L: Effect of heparin and fractions on platelet aggregation. J Clin Invest 65: 64, 1980
Hirsh J, Ofosu F, Buchanan M: The rationale behind the development of low molecular weight heparin derivatives. Semin Thromb Haemostas 11, 13, 1985
Koch KM, Bechstein PB, Fassbinder W, Kaltwasser P, Schoeppe W: Occult blood loss and iron balance in chronic renal failure. Proc Eur Dial Transplant Assoc 12: 681, 1975
Larsson SO: On coagulation and fibrinolysis in uraemic patients on maintenance hemodialysis. Acta Med Scand 189: 453, 1971
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, 1984
Schrader J, Stibbe W, Armstrong VW et al.: Comparison of low molecular weight heparin to standard heparin in hemodialysis/hemofiltration. Kidney Int 33: 890, 1988
Adelman B, Sobel M, Fuhimura Y, Ruggero ZM, Zimmerman TS: Heparin-associated trombocytopenia: observations on the mechanism of platelet aggregation. J Lab Clin Med 113: 204, 1989
Chong BH, Grace CS, Rozenberg MC: Heparin-induced trombocytopenia: effect of heparin platelet antibody on platelets. Br J Haematol 49: 531, 1981
Chong BH, Pitney WR, Castaldi PA: Heparin-induced thrombocytopenia: association of thrombotic complications with heparin-dependent IgG antibody that induces thromboxane synthesis in platelet aggregation. Lancet 2: 1246, 1982
Stead RB, Schafer AI, Rosenberg RD et al.: Heterogeneity of heparin lots associated with thrombocytopenia and thromboembolism. Am J Med 77: 185, 1984
Matzsch T, Bergqvist D, Hedner U, Nilsson B, Ostergaard P: Heparin-induced osteoporosis in rats. Thromb Haemost 56: 293, 1986
Ringe JD, Becker K: Osteoporoseentwicklung bei Heparinlangzeit Therapie. Med Mo Pharm 8: 80, 1955
Majdalani G, Chomat J, Kanchko A, Yanai M, Man NK: Kinetics of technetium-labeled heparin in hemodialyzed patients. Kidney Int 41(Suppl): 5131, 1993
Salzman EW: Low molecular weight heparin. Is small beautiful? N Engl J Med 315: 957, 1986
Thomas DR, Barrowwcliffe TW, Curtis AD. Low molecular weight heparin: a better drug? Haemostasis 16: 87, 1986
Ireland H, Lane DA, Curtis JR: Objective assessment of heparin requirements for hemodialysis in humans. J Lab Clin Med 103: 643, 1984
Schrader J, Stibbe W, Kandt M, Warneke G, Armstrong V, Muller HJ, Scxheler F: Low molecular weight heparin versus standard heparin. A long term study in hemodialysis and hemofiltration patients. Trans Am Soc Artif Intern Organs 36: 28, 1990
Nurmohamed MT, Ten Cate J, Stevens P, Hoeh JA, Lins RL, Ten Cate JW: Long term efficacy and safety of a low molecular weight heparin in chronic hemodialysis patients. A comparison with standard heparin. Trans Am Soc Artif Intern Organs 37: M459, 1991
Lindholm DD, Murray JS: A simplified method of regional heparinization during hemodialysis according to a pre-determined dosage formula. Trans Am Soc Artif Intern Organs 10: 92, 1964
Spencer P, Cozzi E, Easterling RE, Penner JA: Regional heparinization with hollow fiber artificial kidney. Proc AANNT 4: 69, 1977
Gordon LA, Somon ER, Rukes JM, Richards V, Perkins HA: Studies in regional heparinization. N AE J Med 255: 1063, 1956
Blaufox MD, Hampers CL, Merril JP: Heparinization for hemodialysis. Trans Am Soc Artif Intern Organs 12: 207, 1966
Hampers CL, Blaufox MD, Merrill JP: Anticoagulation rebound after hemodialysis. N Engl J Med 275: 776, 1966
Pinnick E, Wiegmanson TE, Diederick DA: Regional citrate anticoagulation for hemodialysis in the patient at high risk for bleeding. N Engl J Med 308: 258, 1983
Lohr JW, Slusher S, Diederich D: Safety of regional citrate hemodialysis in acute renal failure. Am J Kidney Dis 13: 104, 1989
Collart F, Tielemans C, Wens R, Drawta M: Local experience of regional anticoagulation with sodium citrate for hemodialysis in patients at risk of bleeding. Proc Eur Dial Transplant Assoc-Eur Renal Assoc 22: 325, 1985
Morita Y, Johnson RW, Dorn RE, Hall DS: Regional anticoagulation during hemodialysis using citrate. Am J Med Sci 242: 32, 1961
Von Brecht JH, Flanigan MJ, Freeman RM et al.: Regional anticoagulation. Hemodialysis with hypertonic trisodium citrate. Am J Kidney Dis 8: 196, 1986
MacDougall M, Seaton R, Diederich D, Wiegmann T: Effects of both composition and dialyzer membrane on leukocytes and oxygenation during hemodialysis with citrate anticoagulation. Kidney Int 25: 188, 1984
Flanigan MJ, Von Brecht J, Freeman RM, Lim VS: Reducing the hemorrhagic complications of dialysis. A controlled comparison of low dose heparin and citrate anticoagulation. Am J Kidney Dis 9: 147, 1987
Kelleher SP, Schulman G: Severe metabolic alkalosis complicating regional citrate hemodialysis. Am J Kidney Dis 9: 235, 1987
Turney JH, Fewell MR, Williams LC, Parsons V, Weston MJ: Platelet protection and heparin sparing with prot-sacyclin during regular dialysis therapy. Lancet 2: 219, 1980
Turney JH, Woods HF, Weston MJ: The use of prostacyclin in extracorporeal circuits. in Hemostasis, Prostaglandins and Renal Disease, edited by Remuzzi G, Mecca G, de Gaetano G, New York, Raven Press, 1980, p 353
Swartz RD, Flamenbaum W, Dubrow A, Hall JC, Crow JW, Cato A: Epoprostenol during high risk hemodialyis-preventing further bleeding complications. J Clin Pharmacol 28: 818, 1988
Zussman RM, Rubin RH, Cato AE, Cocchetto DM, Crow JW, Tolkoff-Rubin N: Hemodialysis using prostacyclin instead of heparin as the sole antithrombotic agent. N Engl J Med 304: 934, 1981
Hory B, Saint-Hiller Y, Perol JC: Prostacyclin as the sole anti-thrombotic agent for acute renal failure hemodialysis. Nephron 33: 71, 1983
Davies SJ, Hobson SM, Young GA, Turney JH: Acute changes in plasma free fatty acid concentratioon during hemodialysis comparing heparin with epoprostenol as anticoagulant. Proc Eur Dial Transplant Assoc-Eur Renal Assoc 22: 321, 1985
Smith MC, Danviriyasup K, Crow JW, Cato AE, Park GD, Hassid A, Dunn MJ: Prostacyclin substitution for heparin in long-term hemodialysis. Am J Med 73: 669, 1982
Dubrow A, Flamenbaum W, Mittman N, Hall J, Zinn T: Safety and efficacy of epoprostenol (PGI2) versus heparin in hemodialysis. Trans Am Soc Artif Intern Organs 30: 52, 1984
Addonizio VP, Fisher CA, Bowen JC, Palatianos GC, Colman RW, Edmunds LH: Prostacyclin in lieu of anti-coagulation with heparin for extracorporeal circulation. Trans Am Soc Artif Intern Organs 27: 304, 1981
Glaser P, Guesde R, Rouby JJ, Eurin B: Hemodialysis without heparin is possible. Lancet 2: 579, 1980
Sanders PW, Taylor H, Curtis JJ: Hemodialysis without anticoagulation. Am J Kidney Dis 5: 32, 1985
Casati S, Moia, Graziani G et al.: Hemodialysis without anticoagulants: efficiency and hemostatic aspects. Clin Nephrol 21: 102, 1984
Schwab SJ, Omorato JJ, Sharar LR, Dennis PA: Hemodialysis without anticoagulation. One year prospective trial in hospitalized patients at risk of bleeding. Am J Med 83: 405, 1987
Raja RM, Kramer M, Rosenbaum JL et al.: Haemodialysis without heparin infusion using CORDIS DOW 3500 hollow filter. Proc Dial Transplant Forum 10: 39, 1980
Caruana RJ, Raja RM, Bush JV, Kramer MS, Goldsmith SJ: Heparin free dialysis: comparative data and results in high risk patients. Kidney Int 31: 1351, 1987
Ryan KE, Lane DA, Flynn A et al.: antithrombotic properties of dermatan sulphate (MF 701) in haemodialyis for chronic renal failure. Thromb Haemost 68: 563, 1992
Nurmohamed MT, Roggekamp M, Buller HR, Erkamp R, Stevens P, Ten Cate JW: A randomized cross-over study of dermatan sulphate and combination with heparin as anticoagulant in chronic haemodialysis patients. Thromb Haemost 65 (Abstract): 925, 1991
Fernandez F, Van Ryn J, Ofosu FA, Hirsh J, Buchanan MR: The haemorrhagic and antithrombotic effects of dermatan sulphate. Br J Haematol 64: 309, 1986
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Viganò, G., Schieppati, A., Remuzzi, G. (1996). Thrombogenesis and Anticoagulation in Patients Undergoing Chronic Hemodialysis. In: Jacobs, C., Kjellstrand, C.M., Koch, K.M., Winchester, J.F. (eds) Replacement of Renal Function by Dialysis. Springer, Dordrecht. https://doi.org/10.1007/978-0-585-36947-1_13
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