What is the recommended anticoagulation protocol for a patient with impaired renal function undergoing Continuous Renal Replacement Therapy (CRRT) who is at risk of thrombosis?

Anticoagulation Protocol for CRRT to Prevent Thrombosis in Patients with Impaired Renal Function

For patients with impaired renal function undergoing CRRT who are at risk of thrombosis, use regional citrate anticoagulation as first-line therapy unless contraindications exist, in which case use unfractionated or low-molecular-weight heparin. 1

Initial Risk Assessment

Assess bleeding risk and coagulation status before selecting anticoagulation strategy:

• Evaluate for increased bleeding risk, impaired coagulation, and existing systemic anticoagulation before initiating CRRT anticoagulation 1
• Check baseline platelet count, aPTT, INR, and hematocrit to guide anticoagulation selection 2
• Screen for contraindications to citrate including severe liver dysfunction, shock with muscle hypoperfusion, and baseline metabolic abnormalities 3, 4

Anticoagulation Algorithm for Standard Risk Patients

For patients WITHOUT increased bleeding risk or impaired coagulation:

• First-line: Regional citrate anticoagulation is preferred over heparin for CRRT (Grade 2B recommendation) 1
• Citrate provides longer filter lifespan (median 56 hours vs 36 hours with heparin) and reduces bleeding complications compared to heparin 5
• Citrate decreases major bleeding risk by 66% (RR 0.34,95% CI 0.17-0.65) compared to heparin 6

If citrate is contraindicated:

• Use unfractionated heparin or low-molecular-weight heparin as second-line agents 1
• Administer heparin prefilter at 25-30 units/kg bolus followed by 1,500-2,000 units/hour infusion 2
• Monitor aPTT every 4 hours initially, targeting 1.5-2 times normal (approximately 60-85 seconds) 2

Anticoagulation Algorithm for High Bleeding Risk Patients

For patients WITH increased bleeding risk (including thrombocytopenia):

• First-line: Regional citrate anticoagulation is still recommended if no contraindications to citrate exist (Grade 2C recommendation) 1, 3
• Avoid regional heparinization in patients with increased bleeding risk (Grade 2C recommendation) 1
• If citrate is contraindicated, consider running CRRT without anticoagulation rather than using heparin 3, 7
• Anticoagulation-free CRRT achieves similar azotemic control to heparin but with shorter filter lifespan (median 22 hours) 5, 7

Special Population: Heparin-Induced Thrombocytopenia (HIT)

For patients with confirmed or suspected HIT:

• Immediately stop all heparin products and use direct thrombin inhibitors (argatroban) or Factor Xa inhibitors (danaparoid, fondaparinux) (Grade 1A recommendation) 1, 3
• Argatroban is preferred in HIT patients without severe liver failure (Grade 2C recommendation) 1, 3
• Never use unfractionated or low-molecular-weight heparin in confirmed HIT 1

Regional Citrate Anticoagulation Protocol

Citrate administration and monitoring:

• Infuse 2% trisodium citrate at 250 mL/hour via prefilter port, adjusting to maintain post-filter ionized calcium <0.5 mmol/L 8
• Administer central calcium gluconate infusion to maintain systemic ionized calcium at 1.1 mmol/L 8
• Measure post-filter and systemic ionized calcium frequently (every 4-6 hours initially) to titrate citrate and calcium replacement 9, 4

Metabolic monitoring requirements:

• Monitor systemic acid-base balance regularly, particularly in high-risk patients (liver dysfunction, shock) 3, 4
• Check serum sodium levels to prevent hypernatremia associated with citrate anticoagulation 3, 4
• Track electrolytes including potassium, phosphate, and magnesium every 6-12 hours 4
• Monitor for metabolic alkalosis (occurs in 32.5% of patients on citrate) and adjust dialysate bicarbonate concentration accordingly 5

Signs of citrate accumulation (not toxicity):

• Widening gap between systemic and post-filter ionized calcium levels 4
• Rising lactate levels (baseline lactate >6 mmol/L predicts higher citrate accumulation risk) 10
• Citrate accumulation occurred in 52.25% of patients but resolved with protocol adjustments without requiring CRRT discontinuation 10

Contraindications to Citrate

Absolute contraindications:

• Severe liver failure with inability to metabolize citrate 1, 3
• Baseline severe metabolic alkalosis 4

Relative contraindications requiring close monitoring:

• Chronic liver disease (statistically significant increase in citrate accumulation, p≤0.001) 10
• Post-liver transplant recipients (increased citrate accumulation risk, p=0.004) 10
• Shock states with muscle hypoperfusion (not absolute contraindication but requires careful monitoring) 4

Practical Implementation Strategies

Protocol standardization:

• Implement strict written protocols for citrate anticoagulation with mandatory staff education to prevent prescription errors 3, 4
• Use commercial CRRT solutions enriched with phosphate, potassium, and magnesium when using regional citrate anticoagulation 4
• Use dialysate with increased magnesium concentration (magnesium lost as magnesium-citrate complexes in effluent) 3, 4

Filter life optimization:

• Regional citrate provides 61% filter survival at 48 hours compared to 36 hours with heparin 5, 8
• Filter clotting occurs in approximately 33% of patients despite anticoagulation 10
• Target CRRT dose of 25-30 mL/kg/hour for adequate therapy 10

Ongoing Safety Monitoring

Routine monitoring for all CRRT patients:

• Platelet counts daily to detect heparin-induced thrombocytopenia or thrombocytopenia from other causes 2
• Hematocrit and occult blood in stool throughout therapy regardless of anticoagulation method 2
• For citrate: ionized calcium (systemic and post-filter), acid-base status, sodium, and electrolytes every 4-6 hours 4, 8
• For heparin: aPTT or ACT every 4 hours initially, then at appropriate intervals 9, 2

Common pitfalls to avoid:

• Do not rely solely on conventional coagulation parameters (aPTT, PT) to predict filter failure or necessity of anticoagulation 7
• Prevent electrolyte derangements by modulating dialysate composition rather than relying on intravenous supplementation 4
• Avoid subclavian vein access (last choice) due to thrombosis risk; prefer right internal jugular vein 1