- Eugene C Kovalik, MD
Eugene C Kovalik, MD
- Associate Professor of Medicine
- Duke University Medical Center
Hemodialysis and continuous renal replacement therapies require extracorporeal blood flow. Some form of anticoagulation, usually with heparin, is required to prevent thrombosis in the blood circuit. Strategies to minimize the risk of bleeding include low-dose or "minimum heparin" as well as fast-flow "no-heparin" methods. Regional anticoagulation with citrate, prostacyclin, as well as heparin-protamine have also been used. The bleeding tendency induced by these regimens is additive to the commonly present platelet dysfunction associated with advanced renal failure. (See "Platelet dysfunction in uremia".)
Anticoagulation during hemodialysis can be monitored by the determination of activated clotting times (ACTs). However, although ACTs have advantages over whole blood clotting times in that they are interpreted by an automated method with rapid results, they are infrequently used because of quality assurance and regulatory issues.
In general, most outpatient dialysis units do not routinely measure anticoagulation parameters, unless there is an issue with dialyzer clotting or prolonged bleeding following dialysis. Usually, each dialysis unit has a protocol that is followed.
Anticoagulation in routine hemodialysis consists of a standard dose of heparin given as a bolus at the start of the dialysis treatment, with a mid-treatment dose to maintain suitable anticoagulation. Alternatively, heparin modeling can be performed using an initial bolus followed by a constant fixed infusion of heparin to maintain an activated clotting time (ACT) of 200 to 250 seconds (normal = 90 to 140 seconds).
The ACT (activated whole blood clotting time) is performed by addition of an activating agent (eg, celite, kaolin) to a sample of freshly drawn whole blood and measuring the time (in seconds) for formation of a clot (see "Clinical use of coagulation tests"). This therapy ensures systemic anticoagulation throughout the dialysis treatment. It is reliable and requires minimal staff intervention after a patient's heparin dose is determined (based on ACT goal).
- Ouseph R, Brier ME, Ward RA. Improved dialyzer reuse after use of a population pharmacodynamic model to determine heparin doses. Am J Kidney Dis 2000; 35:89.
- Lohr JW, Schwab SJ. Minimizing hemorrhagic complications in dialysis patients. J Am Soc Nephrol 1991; 2:961.
- Sanders PW, Taylor H, Curtis JJ. Hemodialysis without anticoagulation. Am J Kidney Dis 1985; 5:32.
- Stamatiadis DN, Helioti H, Mansour M, et al. Hemodialysis for patients bleeding or at risk for bleeding, can be simple, safe and efficient. Clin Nephrol 2004; 62:29.
- Schwab SJ, Onorato JJ, Sharar LR, Dennis PA. Hemodialysis without anticoagulation. One-year prospective trial in hospitalized patients at risk for bleeding. Am J Med 1987; 83:405.
- Sepulveda S, Davis L, Schwab SJ. Blood transfusion during heparin-free hemodialysis. Kidney Int 1997; 51:2018.
- Swartz RD, Port FK. Preventing hemorrhage in high-risk hemodialysis: regional versus low-dose heparin. Kidney Int 1979; 16:513.
- GORDON LA, PERKINS HA, RICHARDS V, et al. Studies in regional heparinization. II. Artificial-kidney hemodialysis without systemic heparinization; preliminary report of a method using simultaneous infusion of heparin and protamine. N Engl J Med 1956; 255:1063.
- Maher JF, Lapierre L, Schreiner GE, et al. Regional heparinization for hemodialysis. N Engl J Med 1963; 268:451.
- Lindholm DD, Murray JS. A simplified method of regional heparinization during hemodialysis according to a predetermined dosage formula. Trans Am Soc Artif Intern Organs 1964; 10:92.
- Spencer P, Cozzi E, Easterling RE, Penner JA. Regional heparinization with the hollow fiber artificial kidney. Proc Am Assoc Nephrol Nurses Technicians 1977; 4:69.
- Congdon JE, Kardinal CG, Wallin JD. Monitoring heparin therapy in hemodialysis. A report on the activated whole blood coagulation time tests. JAMA 1973; 226:1529.
- Blaufox MD, Hampers CL, Merrill JP. Rebound anticoagulation occurring after regional heparinization for hemodialysis. Trans Am Soc Artif Intern Organs 1966; 12:207.
- Pinnick RV, Wiegmann TB, Diederich DA. Regional citrate anticoagulation for hemodialysis in the patient at high risk for bleeding. N Engl J Med 1983; 308:258.
- von Brecht JH, Flanigan MJ, Freeman RM, Lim VS. Regional anticoagulation: hemodialysis with hypertonic trisodium citrate. Am J Kidney Dis 1986; 8:196.
- Janssen MJ, Huijgens PC, Bouman AA, et al. Citrate versus heparin anticoagulation in chronic haemodialysis patients. Nephrol Dial Transplant 1993; 8:1228.
- Flanigan MJ, Von Brecht J, Freeman RM, Lim VS. Reducing the hemorrhagic complications of hemodialysis: a controlled comparison of low-dose heparin and citrate anticoagulation. Am J Kidney Dis 1987; 9:147.
- Apsner R, Buchmayer H, Lang T, et al. Simplified citrate anticoagulation for high-flux hemodialysis. Am J Kidney Dis 2001; 38:979.
- Apsner R, Buchmayer H, Gruber D, Sunder-Plassmann G. Citrate for long-term hemodialysis: prospective study of 1,009 consecutive high-flux treatments in 59 patients. Am J Kidney Dis 2005; 45:557.
- Morgera S, Haase M, Ruckert M, et al. Regional citrate anticoagulation in continuous hemodialysis--acid-base and electrolyte balance at an increased dose of dialysis. Nephron Clin Pract 2005; 101:c211.
- Ahmad S, Callan R, Cole JJ, Blagg CR. Dialysate made from dry chemicals using citric acid increases dialysis dose. Am J Kidney Dis 2000; 35:493.
- Tu A, Ahmad S. Heparin-free hemodialysis with citrate-containing dialysate in intensive care patients. Dial Transplant 2000; 29:620.
- Swartz RD, Flamenbaum W, Dubrow A, et al. Epoprostenol (PGI2, prostacyclin) during high-risk hemodialysis: preventing further bleeding complications. J Clin Pharmacol 1988; 28:818.
- Caruana RJ, Smith MC, Clyne D, et al. Controlled study of heparin versus epoprostenol sodium (prostacyclin) as the sole anticoagulant for chronic hemodialysis. Blood Purif 1991; 9:296.
- Ota K, Kawaguchi H, Takahashi K, Ito K. A new prostacyclin analogue - an anticoagulant applicable to hemodialysis. Trans Am Soc Artif Intern Organs 1983; 29:419.
- Matsuo T, Kario K, Nakao K, et al. Anticoagulation with nafamostat mesilate, a synthetic protease inhibitor, in hemodialysis patients with a bleeding risk. Haemostasis 1993; 23:135.
- Lim W, Cook DJ, Crowther MA. Safety and efficacy of low molecular weight heparins for hemodialysis in patients with end-stage renal failure: a meta-analysis of randomized trials. J Am Soc Nephrol 2004; 15:3192.
- Vanuytsel JL, Lins RL, Zachée P, et al. Comparison of different routes of administration of nadroparin in hemodialysis. Clin Nephrol 1999; 52:322.
- Janssen MJ, Deegens JK, Kapinga TH, et al. Citrate compared to low molecular weight heparin anticoagulation in chronic hemodialysis patients. Kidney Int 1996; 49:806.
- Schrader J, Stibbe W, Kandt M, et al. Low molecular weight heparin versus standard heparin. A long-term study in hemodialysis and hemofiltration patients. ASAIO Trans 1990; 36:28.
- Polkinghorne KR, McMahon LP, Becker GJ. Pharmacokinetic studies of dalteparin (Fragmin), enoxaparin (Clexane), and danaparoid sodium (Orgaran) in stable chronic hemodialysis patients. Am J Kidney Dis 2002; 40:990.
- van Wyk V, Badenhorst PN, Luus HG, Kotzé HF. A comparison between the use of recombinant hirudin and heparin during hemodialysis. Kidney Int 1995; 48:1338.
- Fischer KG, van de Loo A, Böhler J. Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis. Kidney Int Suppl 1999; :S46.
- Evenepoel P, Dejagere T, Verhamme P, et al. Heparin-coated polyacrylonitrile membrane versus regional citrate anticoagulation: a prospective randomized study of 2 anticoagulation strategies in patients at risk of bleeding. Am J Kidney Dis 2007; 49:642.
- European Best Practice Guidelines Expert Group on Hemodialysis, European Renal Association. Section II. Haemodialysis adequacy. Nephrol Dial Transplant 2002; 17 Suppl 7:16.
- Murray PT, Reddy BV, Grossman EJ, et al. A prospective comparison of three argatroban treatment regimens during hemodialysis in end-stage renal disease. Kidney Int 2004; 66:2446.
- Henny CP, ten Cate H, Surachno S, et al. The effectiveness of a low molecular weight heparinoid in chronic intermittent haemodialysis. Thromb Haemost 1985; 54:460.
- Weijmer MC, van den Dorpel MA, Van de Ven PJ, et al. Randomized, clinical trial comparison of trisodium citrate 30% and heparin as catheter-locking solution in hemodialysis patients. J Am Soc Nephrol 2005; 16:2769.
- Farthing C, Krishnan M, Mayne T, et al. Tego Connectors Reduce Heparin Use Without Affecting Blood Flow Rate Compared to Traditional Central Venous Catheter Locks. American Nephrology Nurses' Association 43rd National Symposium. Orlando, FL. April 29-May 2, 2012.
- O'Shea SI, Ortel TL, Kovalik EC. Alternative methods of anticoagulation for dialysis-dependent patients with heparin-induced thrombocytopenia. Semin Dial 2003; 16:61.
- STANDARD ANTICOAGULATION
- ANTICOAGULATION IN HEMODIALYSIS PATIENTS AT RISK FOR BLEEDING
- No-heparin hemodialysis
- Minimum-dose heparin
- Regional anticoagulation with protamine reversal
- Regional citrate anticoagulation
- Citrate dialysate
- Prostacyclin regional anticoagulation
- - Low-molecular-weight heparin
- - Recombinant hirudin anticoagulation
- - Heparin-coated membranes
- CONTINUOUS HEMODIALYSIS MODALITIES
- HEPARIN-INDUCED THROMBOCYTOPENIA
- Non-warfarin oral anticoagulants
- Catheter lock issues
- SUMMARY AND RECOMMENDATIONS