What is the recommended unfractionated heparin regimen for routine intermittent hemodialysis in adult patients without high bleeding risk or heparin‑induced thrombocytopenia, and how should the dosing be adjusted for patients with increased bleeding risk or suspected/confirmed HIT?

Heparin Use in Dialysis

Standard Anticoagulation for Routine Hemodialysis

For adult patients without high bleeding risk or HIT undergoing routine intermittent hemodialysis, unfractionated heparin (UFH) remains the recommended first-line anticoagulant, administered as an initial bolus of 25-50 units/kg followed by continuous infusion of 500-1500 units/hour. 1

Rationale for UFH as Standard of Care

• UFH does not require dose adjustment for renal impairment and is not cleared by dialysis, making it ideal for patients with complete renal failure 1, 2
• The short half-life (1-2 hours after IV injection) allows rapid reversal if bleeding occurs 1
• UFH is the most cost-effective option with decades of proven safety and efficacy in outpatient hemodialysis 3, 4
• Most centers adjust dosing pragmatically by visual inspection of the dialyzer for clots and monitoring time to hemostasis after needle removal, rather than routine laboratory monitoring 4, 5

Practical Administration Details

• Administer the bolus dose a few minutes before connecting the patient to the circuit to ensure adequate mixing with blood 4
• Stop the heparin infusion 30-60 minutes before the end of the dialysis session, adjusting based on time required for needle puncture sites to stop bleeding 4
• Routine aPTT monitoring is not necessary for standard outpatient hemodialysis unless bleeding complications arise 4, 5

Low Molecular Weight Heparin as Alternative

LMWH can be used as an alternative to UFH and has become the anticoagulant of choice in Europe due to ease of administration and reliability, though it requires careful consideration in dialysis patients. 6, 3

Advantages of LMWH

• More predictable pharmacokinetics and pharmacodynamics compared to UFH 3, 5
• Lower rates of bleeding episodes and heparin-induced thrombocytopenia than UFH 3, 5
• Does not require routine laboratory monitoring in most cases 5

Critical Caveats for LMWH Use

• LMWH accumulates in severe renal impairment (CrCl <30 mL/min) with bleeding risk up to twice as high 1
• Anti-Xa level monitoring is recommended when using LMWH in dialysis patients to avoid accumulation 1
• The National Comprehensive Cancer Network recommends avoiding standard LMWH doses in dialysis patients without anti-Xa monitoring due to severe bleeding risk from accumulation 1

Patients with Increased Bleeding Risk

For patients with increased bleeding risk who are not receiving systemic anticoagulation, regional citrate anticoagulation is the preferred alternative over heparin or other anticoagulants. 6

Regional Citrate Advantages

• Provides anticoagulation limited to the extracorporeal circuit without systemic effects 1
• Demonstrates similar efficacy to heparin with superior safety profile, including reduced bleeding and reduced HIT risk 6, 1
• More cost-effective than alternative non-heparin anticoagulants 1
• Familiar to clinicians and widely available 6

When to Avoid Citrate

• Citrate is not appropriate for patients requiring systemic anticoagulation (only for circuit anticoagulation) 6, 1
• Contraindicated in patients with severe liver failure or metabolic complications 1

Patients with Suspected or Confirmed HIT

For patients with acute HIT requiring hemodialysis, all heparin must be stopped immediately and argatroban should be initiated as first-line alternative anticoagulant. 6

Argatroban Dosing for Acute HIT

• Standard dosing: 250 μg/kg bolus for intermittent hemodialysis or 100 μg/kg for continuous hemodialysis, followed by continuous infusion 2
• Optimal dosing based on clinical experience: 5 mg bolus with 0.15 mg/kg/hour infusion, adjusted based on aPTT monitoring 2, 7
• Target aPTT of 1.5-3 times baseline, checking 2 hours after starting infusion and after any dose adjustment 8

Why Argatroban is Preferred in HIT

• Argatroban undergoes hepatic metabolism rather than renal clearance, making it ideal for dialysis patients 6, 8
• Dialytic clearance by high-flux membranes is clinically insignificant 6
• Prospective studies show low rates of new thrombosis (0-4%) and major bleeding (0-6%) 6, 1
• Does not require dose adjustment for renal impairment (though reduce dose by 50% if severe liver disease present) 8

Alternative Agents for Acute HIT

Danaparoid can be used when argatroban is unavailable, though it has more limitations in renal failure. 6

• Dosing: 3,750 units bolus (2,500 units if weight <55 kg) before first two sessions, then 3,000 units (2,000 units if weight <55 kg) for subsequent sessions 6, 2
• Critical limitation: Danaparoid is renally cleared and accumulates in renal failure, making it less ideal than argatroban 6, 2
• Thrombosis occurred in 7% and major bleeding in 6% in retrospective studies 6

Bivalirudin is an acceptable third-line alternative with dose reduction required: 1.0 mg/kg/hour for CrCl <30 mL/min and 0.25 mg/kg/hour for patients on hemodialysis 1

Subacute or Remote HIT (Circuit-Only Anticoagulation)

For patients with subacute HIT A, subacute HIT B, or remote HIT who require anticoagulation only for the dialysis circuit (not systemic anticoagulation), regional citrate is preferred over heparin or other non-heparin anticoagulants. 6, 1

• This recommendation applies when the prothrombotic state of HIT appears to have resolved (platelet count normalized) 6
• If citrate is contraindicated, use argatroban or danaparoid 6

Special Situations and Pitfalls

Inflammatory States (COVID-19, Sepsis)

• Higher heparin doses or therapeutic anticoagulation may be required due to heparin resistance from elevated acute phase reactants (fibrinogen, C-reactive protein) 6, 1
• Heparin resistance is defined as requiring >35,000 units/day to achieve therapeutic range 6
• Consider switching to alternative anticoagulants if standard doses prove inadequate 6

Critical Pitfalls to Avoid

• Never withhold therapeutic anticoagulation in HIT due to thrombocytopenia - the thrombotic risk (30-50%) far exceeds bleeding risk 8
• All forms of heparin must be discontinued in HIT, as LMWH cross-reacts with HIT antibodies in 80-90% of cases 8
• Do not start warfarin until platelet count recovers to >150,000/μL in HIT patients, as vitamin K antagonists can cause venous limb gangrene in acute HIT 6, 8
• Avoid lepirudin in dialysis patients due to renal clearance, prolonged half-life, and increased bleeding risk 6
• Fondaparinux and rivaroxaban should be avoided in acute HIT requiring dialysis because their anticoagulant effect depends on renal clearance 1

Monitoring Recommendations

• For UFH in inflammatory states where aPTT may be unreliable, use anti-Xa assay with target 0.5-0.7 IU/mL for therapeutic dosing 1
• Monitor platelet count once or twice weekly if standard-dose UFH is used to detect HIT 1
• For argatroban, check aPTT every 2 hours initially until stable 8