What is the recommended dose of factor 8 (FVIII) for a major surgery in a patient with hemophilia?

Factor VIII Dosing for Major Surgery in Hemophilia A

For major surgery in hemophilia A patients without inhibitors, administer a preoperative bolus of Factor VIII to achieve levels of 80-100 IU/dL (approximately 40-50 IU/kg for adults), followed by either continuous infusion or bolus dosing to maintain trough levels ≥50 IU/dL for 7-14 days postoperatively. 1

Preoperative Dosing

• Initial bolus dose: Calculate using the formula: Dose (IU) = body weight (kg) × desired Factor VIII rise (IU/dL) × 0.5 for patients ≥12 years 1
• For children <12 years: Use the formula: Dose (IU) = body weight (kg) × desired Factor VIII rise (IU/dL) × 0.6 1
• Target preoperative levels: Achieve 70-90 IU/dL (some sources recommend 80-100 IU/dL) measured 30-60 minutes before surgery 1, 2
• Confirm target achievement: Measure Factor VIII levels preoperatively to verify levels ≥80 IU/dL before proceeding 1

Postoperative Maintenance: Bolus vs. Continuous Infusion

Either approach is acceptable, as both have similar efficacy for hemostasis. 3, 1

Bolus Infusion Approach

• Administer Factor VIII every 8-12 hours to maintain trough levels ≥50 IU/dL 1
• Standard practice for Extended Half-Life (EHL) Factor VIII products, as continuous infusion is not validated for EHL concentrates 3, 1
• Easier to implement in settings without infusion pumps 3

Continuous Infusion Approach

• Initial rate: Start at approximately 4 IU/kg/hour after the loading bolus 4, 5
• Dose adjustment: Calculate clearance daily and adjust infusion rate based on actual Factor VIII levels to maintain target range 3, 5
• Resource advantage: Consumes 30-40% less Factor VIII concentrate compared to bolus dosing, which is relevant in resource-limited settings 3, 1
• Requirements: Requires validated Factor VIII concentrate suitable for continuous infusion per manufacturer instructions, availability of infusion pumps, and regular Factor VIII level monitoring 3
• Clearance changes: Expect progressive decrease in Factor VIII clearance over the first 5 days (from approximately 3.2 to 1.7 mL/kg/hour), allowing for dose reduction 5

Postoperative Target Levels and Duration

• Days 1-3 postoperatively: Maintain Factor VIII trough levels ≥50 IU/dL (some protocols use 50-80 IU/dL) 1, 6
• Days 4-7: Continue replacement to maintain levels ≥50 IU/dL 1
• Total duration: Continue Factor VIII replacement for 7-14 days total or until wound healing is complete 1
• Daily monitoring: Measure Factor VIII levels daily for the first 7-14 days postoperatively 1

Critical Safety Considerations

• Avoid excessive peaks: Do not exceed Factor VIII levels of 120 IU/dL to minimize thrombotic risk 1
• Surgery location: Perform surgery only at centers with expertise in hemophilia management 1
• Inhibitor screening: Ensure inhibitor testing is completed preoperatively; this recommendation applies only to patients without inhibitors 3

Special Population: Patients on Emicizumab

• For hemophilia A patients on emicizumab prophylaxis undergoing surgery: Use bolus infusions of Factor VIII only, as this is the only approach with published safety data in this population 1
• Continuous infusion is not validated for patients on emicizumab 3

Common Pitfalls to Avoid

• Inadequate preoperative level confirmation: Always measure Factor VIII levels before surgery rather than relying solely on dose calculations, as recovery can vary (expected recovery approximately 1.7 IU/mL per IU/kg for FVIII) 4
• Using continuous infusion with EHL products: This is not validated and should be avoided 3, 1
• Premature discontinuation: Continue replacement until wound healing is complete, typically 7-14 days, not just until hospital discharge 1
• Inadequate monitoring with continuous infusion: Requires daily Factor VIII level measurements and clearance calculations for dose adjustment 3, 5