What heparin‑free dialysis regimen should be used for a patient requiring hemodialysis who has contraindications to systemic heparin (e.g., active bleeding, recent major surgery, severe thrombocytopenia, heparin‑induced thrombocytopenia, or high risk of hemorrhage)?

Heparin-Free Hemodialysis: Recommended Regimens

For patients with contraindications to systemic heparin, regional citrate anticoagulation is the preferred first-line strategy, offering equivalent circuit patency to heparin with superior safety and no systemic anticoagulation effects. 1

Primary Recommendation: Regional Citrate Anticoagulation

Regional citrate should be used as the preferred alternative for patients at high bleeding risk or those who cannot receive heparin, as it provides anticoagulation limited to the extracorporeal circuit without systemic effects. 1 This approach demonstrates similar efficacy to heparin with reduced bleeding risk and eliminates the risk of heparin-induced thrombocytopenia (HIT). 1

Key Advantages of Regional Citrate:

• Provides circuit anticoagulation without systemic effects, eliminating bleeding risk while maintaining dialysis efficacy 2
• More cost-effective than alternative non-heparin anticoagulants 1
• Reduced risk of HIT compared to heparin 1

Critical Limitation:

• Citrate is NOT appropriate for patients with acute HIT who require systemic (rather than regional) anticoagulation 1

Alternative Strategies When Citrate is Contraindicated

For Acute Heparin-Induced Thrombocytopenia (HIT):

Argatroban is the first-line alternative anticoagulant for acute HIT requiring dialysis, with standard therapeutic doses requiring no adjustment for renal failure. 1, 3

Argatroban Advantages:

• Lacks renal clearance, making it ideal for dialysis patients 1
• Clinically insignificant dialytic removal by high-flux membranes 1
• Low complication rates: new thrombosis in 0-4% and major bleeding in 0-6% of patients 1

Alternative Agents for Acute HIT:

• Danaparoid or bivalirudin can be used but have more limitations 3, 1
• Danaparoid requires bolus dosing of 3750 units (2500 units if weight <55 kg) before first two sessions, then 3000 units (2000 units if weight <55 kg) for subsequent sessions 3
• Avoid fondaparinux and rivaroxaban in acute HIT with dialysis due to their dependence on renal clearance 3, 4

For Subacute or Remote HIT:

Regional citrate is preferred over heparin or other non-heparin anticoagulants for patients with subacute HIT A, subacute HIT B, or remote HIT who require anticoagulation only for the dialysis circuit. 3, 1

Heparin-Free Hemodialysis (No Anticoagulation)

When neither citrate nor alternative anticoagulants are feasible, heparin-free hemodialysis with saline flushes is an appropriate alternative that achieves adequate clearance (Kt/V >1.2) without increasing bleeding complications. 2

Optimizing Heparin-Free Dialysis:

Heparin-coated dialysis membranes (AN69ST with pre-dialysis heparin coating) significantly reduce clotting events compared to intermittent saline flushes alone (odds ratio 0.3, p<0.001). 5 This approach:

• Increases odds of completing >3 hour dialysis sessions 5
• Improves complete blood restitution 5
• Is safe and effective for patients with contraindication to systemic anticoagulation 5

Important caveat: Results are not generalizable to patients with active bleeding, since weak heparinemia may occur with coated membranes. 5

Conventional HD vs. Predilution HDF:

Standard hemodialysis with polysulfone membrane is superior to predilution hemodiafiltration for heparin-free dialysis, with only 12% premature termination versus 23% with HDF (p=0.04). 6 Conventional heparin-free hemodialysis can safely achieve 4-hour sessions in most high bleeding-risk patients. 6

Clinical Algorithm for Selection

1. First-line: Regional citrate anticoagulation (unless acute HIT requiring systemic anticoagulation) 1, 2

2. For acute HIT: Argatroban → danaparoid or bivalirudin as alternatives 3, 1

3. For subacute/remote HIT: Regional citrate preferred 3, 1

4. When citrate and systemic anticoagulants contraindicated:

   • Heparin-coated membrane (AN69ST) with saline flushes 5
   • Standard HD preferred over predilution HDF 6

5. Last resort: Heparin-free HD with intermittent saline flushes alone 2

Common Pitfalls to Avoid

• Never use low-molecular-weight heparin as an alternative when heparin is contraindicated – both are heparin products sharing the same contraindications 4
• Do not use regional citrate for acute HIT requiring systemic anticoagulation 3, 1
• Avoid rivaroxaban as first-line alternative due to limited data and high renal dependence 4
• Do not use "regional heparinization with protamine reversal" – this outdated approach has higher bleeding complications (19%) compared to other methods 7

Monitoring Requirements

• For argatroban: Monitor activated clotting times or systemic aPTT to guide dosing 4
• Avoid argatroban in severe liver failure due to hepatic metabolism 4
• Have protamine sulfate immediately available if any heparin exposure occurs 2