What is the recommended dose of factor VIII to administer before surgery in a patient with unknown type von Willebrand syndrome?

Factor VIII Dosing for Surgery in Unknown Type Von Willebrand Syndrome

For patients with unknown type von Willebrand syndrome undergoing surgery, a VWF/FVIII concentrate (such as Humate-P) should be administered at a loading dose of 40-60 IU VWF:RCo/kg to achieve target VWF activity levels of ≥80-100 IU/dL for major procedures.

Rationale for Treatment Selection

When managing patients with von Willebrand syndrome (VWD) of unknown type before surgery, the safest approach is to treat as if the patient has a more severe form of the disease. This is because:

• Human-derived medium-purity FVIII concentrates complexed to von Willebrand factor (Humate-P) are approved for pediatric patients with VWD for the prevention of excessive bleeding during and after surgery 1
• This applies to patients with severe VWD and patients with mild to moderate VWD in whom desmopressin is known or suspected to be inadequate 1
• Without knowing the specific VWD type, desmopressin response cannot be predicted, making VWF/FVIII concentrate the safer option

Dosing Recommendations

Initial Loading Dose:

• For major surgery: 60-61 IU VWF:RCo/kg 1, 2
• For minor surgery: 40-43 IU VWF:RCo/kg 1, 2

Target Levels:

• Aim for VWF:RCo levels of ≥80-100 IU/dL for major procedures 3
• Minimum VWF activity level of 50 IU/dL is required for adequate hemostasis 3
• For patients with history of severe bleeding, target VWF activity level of ≥80 IU/dL 3

Maintenance Dosing:

• Multiple doses may be required, with a median of 10 doses (range 2-55) typically administered per subject depending on the procedure 2
• Monitor FVIII levels closely as repeated doses of FVIII-VWF concentrate may lead to very high FVIII levels due to the combined effect of exogenous FVIII and endogenous FVIII release induced by the infused VWF 4

Monitoring Parameters

1. Pre-operative assessment:

   • VWF ristocetin cofactor (VWF:RCo) activity
   • VWF antigen (VWF:Ag)
   • Factor VIII coagulant activity (FVIII:C)

2. Post-infusion monitoring:

   • VWF:RCo levels (target ≥80-100 IU/dL for major surgery)
   • FVIII levels (to avoid excessive levels that might increase thrombotic risk)
   • Clinical assessment for bleeding

Important Considerations

• Pharmacokinetics: Median terminal VWF:RCo half-life is approximately 11.7 hours, and median incremental in vivo recovery is 2.4 IU/dL per IU/kg infused 2

• Duration of therapy: Continue treatment for 7-14 days for major surgery or until wound healing is complete

• Potential complications: Major hemorrhage can occur in approximately 10% of cases despite achieving target VWF and FVIII levels 2, 5, necessitating close monitoring

• Safety profile: Adverse events related to VWF/FVIII concentrate treatment are generally mild and of short duration 2

Special Situations

For patients with known VWD type:

• Type 1 VWD: Consider desmopressin (DDAVP) 0.3 μg/kg as first-line if responsive 3
• Type 2B VWD: VWF-containing factor concentrates are the treatment of choice 3
• Type 3 VWD: Always use VWF-containing factor concentrates 3

For emergency surgery without time for testing, treat as if the patient has a more severe form of VWD with VWF/FVIII concentrate at the higher end of the dosing range.