What anticoagulant is recommended for patients undergoing hemodialysis?

Anticoagulation in Hemodialysis

Unfractionated heparin (UFH) is the recommended standard anticoagulant for hemodialysis procedures, administered as an initial bolus of 25-50 units/kg followed by continuous infusion of 500-1500 units/hour. 1

Standard Anticoagulation Protocol

First-Line: Unfractionated Heparin

• UFH remains the anticoagulant of choice due to its low cost, proven efficacy, reversibility, and lack of renal clearance 1, 2
• The National Kidney Foundation specifically endorses UFH as the preferred agent in patients with severe renal insufficiency (creatinine clearance <30 mL/min) because it requires no dose adjustment for renal function 3
• UFH is not cleared by dialysis and its metabolism is primarily hepatic, making it ideal for this population 1, 3
• When properly monitored, UFH provides a relatively safe and economical choice for long-term hemodialysis anticoagulation 2

Monitoring and Target Levels

• The American Society of Nephrology recommends monitoring with activated partial thromboplastin time (aPTT), targeting 1.5 to 2.5 times the normal value 3
• Anti-Xa activity levels of 0.3 to 0.7 IU/mL are considered sufficient for adequate anticoagulation during the procedure 4
• UFH has a terminal half-life of approximately 54 minutes, with anti-Xa activity dropping below 0.1 IU/mL within 90 minutes after the session ends 4

Alternative Anticoagulation Options

Low Molecular Weight Heparins (LMWHs)

• LMWHs can be used but require careful dosing and anti-Xa level monitoring due to renal clearance and accumulation risk 1
• Critical caveat: LMWHs are contraindicated or require dose adjustment when creatinine clearance <30 mL/min, with bleeding risk up to twice as high in severe renal impairment 1
• The National Comprehensive Cancer Network specifically recommends avoiding standard LMWH doses in dialysis patients without anti-Xa monitoring, as accumulation leads to severe bleeding 1
• Despite these concerns, some evidence suggests LMWH may be associated with fewer bleeding and clotting episodes compared to UFH when properly dosed 5

Regional Citrate Anticoagulation

• Regional citrate anticoagulation is the preferred alternative for patients with high bleeding risk or heparin-induced thrombocytopenia (HIT) 1
• The American Society of Hematology recommends citrate regional over heparin in patients with subacute, remote, or past HIT who are receiving renal replacement therapy 1
• Citrate is not appropriate for patients with acute HIT who require systemic anticoagulation instead of regional anticoagulation 1

Management of Heparin-Induced Thrombocytopenia

Acute HIT During Dialysis

• For acute HIT requiring dialysis, argatroban is the ideal choice due to its lack of renal clearance and clinically insignificant dialytic removal by high-flux membranes 1, 6
• The American Society of Hematology suggests treatment with argatroban, danaparoid, or bivalirudin over other non-heparin anticoagulants 1, 6
• Argatroban demonstrates low rates of new thrombosis (0%-4%) and major bleeding (0%-6%) in prospective studies 1, 6

Dosing for Alternative Agents

• Argatroban: Bolus dose of 100 μg/kg for continuous hemodialysis or 250 μg/kg for intermittent hemodialysis, followed by continuous infusion 3
• Danaparoid: Bolus dose of 3750 U (2500 U if weight <55 kg) before the first two sessions and 3000 U (2000 U if weight <55 kg) thereafter 3
• Bivalirudin: Requires dose reduction to 1.0 mg/kg/hour for CrCl <30 mL/min, and 0.25 mg/kg/hour for patients on hemodialysis 1

Special Clinical Situations

High-Risk Bleeding Patients

• Use regional citrate anticoagulation as first alternative 1
• Consider low-dose UFH protocols with careful monitoring 2
• Heparin-coated dialyzers may reduce systemic anticoagulation requirements, though systemic heparin is usually still needed 7

Inflammatory States (e.g., COVID-19)

• The International Society on Thrombosis and Haemostasis recommends higher heparin doses or therapeutic anticoagulation for inflammatory states that increase filter clotting despite standard anticoagulation 1

Patients with Liver Dysfunction

• Patient liver function should be considered when selecting anticoagulants, as hepatic dysfunction may affect bleeding risk and anticoagulant metabolism 1
• Argatroban's pharmacokinetic profile remains similar in patients with renal failure compared to those with normal renal function 6

Common Pitfalls to Avoid

• Never use standard LMWH doses without anti-Xa monitoring in dialysis patients due to accumulation risk 1
• Avoid rivaroxaban and dabigatran in hemodialysis patients, as they are associated with increased major bleeding risk compared to warfarin 1
• Do not use heparin or LMWH in patients with a history of HIT due to risk of recurrence 6
• Be cautious with lepirudin in dialysis patients due to its prolonged half-life and potential for accumulation between dialysis sessions 6