What is the role of heparin (unfractionated heparin) in hemodialysis?

Heparin in Hemodialysis

Unfractionated heparin (UFH) is the standard anticoagulant for hemodialysis, administered as an initial bolus of 25-50 units/kg followed by continuous infusion of 500-1500 units/hour, and it remains the preferred choice due to its low cost, proven efficacy, reversibility, and lack of need for dose adjustment in renal impairment. 1, 2

Standard Heparin Protocol for Routine Hemodialysis

Dosing regimen:

• Initial bolus: 25-50 units/kg administered a few minutes before connecting the patient to the extracorporeal circuit 1, 3
• Continuous infusion: 500-1500 units/hour during the dialysis session 1
• Timing: Stop the heparin infusion 30-60 minutes before the end of dialysis to minimize bleeding at needle puncture sites 3

Key advantages of UFH:

• Does not require dose adjustment for renal impairment as metabolism is primarily hepatic 4
• Not cleared by dialysis itself 1
• Can be reversed with protamine sulfate if bleeding occurs 5
• Decades of clinical experience demonstrating safety and effectiveness 3, 6

Monitoring Anticoagulation

For routine outpatient hemodialysis, laboratory monitoring is NOT routinely indicated and most centers use a pragmatic approach based on visual inspection 7, 3:

• Inspect the dialyzer header and venous air detector chamber for clots during treatment 3
• Assess time to hemostasis at needle puncture sites after treatment 3
• Adjust doses based on these clinical observations rather than laboratory values 3

When laboratory monitoring IS indicated (select high-risk patients only) 7:

• Patients with extremes of body weight
• History of repeated circuit clotting
• History of bleeding complications
• Target aPTT: 1.5 to 2.5 times normal value 4, 5
• Alternative monitoring: activated clotting time (ACT) or anti-factor Xa levels 7

Alternative Anticoagulation Strategies

For Patients with High Bleeding Risk

Regional citrate anticoagulation is the preferred alternative for patients at high bleeding risk or those who cannot receive heparin 1, 8:

• Provides anticoagulation only within the extracorporeal circuit
• Avoids systemic anticoagulation of the patient 9
• Requires equipment that supports citrate protocols 4

Heparin-free dialysis may be performed in patients with active bleeding 6:

• Use saline flushes to maintain circuit patency 5
• Requires careful monitoring for circuit clotting 6
• Consider modifications to dialyzer membranes and dialysate composition 9

For Patients with Heparin-Induced Thrombocytopenia (HIT)

For acute HIT requiring dialysis, use argatroban as first-line alternative 5, 1, 4:

• Bolus dose: 250 μg/kg for intermittent hemodialysis or 100 μg/kg for continuous hemodialysis 1, 4
• Continuous infusion: Adjusted based on aPTT monitoring (target aPTT 50-60 seconds) 5
• Rationale: Argatroban is not renally cleared and dialytic clearance by high-flux membranes is clinically insignificant 5, 1
• Safety profile: Low rates of new thrombosis (0%-4%) and major bleeding (0%-6%) 1

Danaparoid is an acceptable alternative 5, 1, 4:

• Bolus dose: 3,750 units (2,500 units if weight <55 kg) before the first two sessions, then 3,000 units (2,000 units if weight <55 kg) for subsequent sessions 1, 4
• Caution: Accumulates in renal failure due to renal clearance, making it less ideal than argatroban 5, 1

For subacute, remote, or past HIT, regional citrate anticoagulation is preferred over argatroban or danaparoid 1:

• Citrate is not appropriate for acute HIT patients who require systemic anticoagulation 1

Low Molecular Weight Heparins (LMWHs)

LMWHs can be used but require careful consideration 1, 10:

• May be given as a single initial bolus injection, generally adequate 10
• Critical limitation: Contraindicated or require dose adjustment when creatinine clearance <30 mL/min 1
• Bleeding risk: Up to twice as high in severe renal impairment 1
• Monitoring required: Anti-Xa level monitoring recommended to avoid accumulation 1, 7
• Avoid standard LMWH doses in dialysis patients without anti-Xa monitoring due to severe bleeding risk from accumulation 1

Common Pitfalls and How to Avoid Them

Inadequate mixing of heparin with blood:

• Administer the bolus a few minutes BEFORE connecting the patient to the circuit 3
• Ensure thorough mixing of the heparin infusion with blood flow 3
• Heparin is negatively charged and binds to plasma proteins, leukocytes, and plastic, requiring adequate mixing for optimal anticoagulation 3

Dilution of blood samples:

• When drawing predialysis BUN samples from catheters, withdraw and discard 10 mL (adults) or 3-5 mL (pediatrics) before collecting the sample 5
• Prevents contamination with heparin or saline that would falsely lower measurements 5

Inappropriate use of warfarin or DOACs:

• For systemic anticoagulation needs (e.g., atrial fibrillation), apixaban is preferred over warfarin in dialysis patients 1
• Rivaroxaban and dabigatran should be avoided due to increased major bleeding risk 1
• Warfarin shows no stroke reduction benefit but increases bleeding risk in ESRD patients 1

Failure to stop heparin infusion early enough:

• Stop infusion 30-60 minutes before end of treatment to allow adequate hemostasis at access sites 3
• Adjust timing based on individual patient bleeding tendency 3