Perioperative Management of Bleeding in Patients with von Willebrand Disease Using Coagulation Factors

Introduction

Von Willebrand disease (VWD) is the most common congenital bleeding disorder, caused by a quantitative (type 1 and 3) or qualitative (type 2) deficiency of von Willebrand factor. Bleeding manifestations vary in intensity, often being mild, and most affected individuals do not seek medical attention. However, even these patients are at risk of severe bleeding in case of injuries, surgeries, and invasive procedures. Therefore, perioperative management of potential bleeding is crucial for them.

Current therapy for VWD focuses on normalizing the levels of von Willebrand factor (VWF) and coagulation factor VIII (FVIII) in cases of acute bleeding, post-surgical intervention, or trauma. The administration of coagulation factors is the treatment of choice for perioperative care in patients with type 2A, 2B, and 3. In patients with types 1, 2M, and 2N, administration is indicated in case of inadequate therapeutic response to desmopressin or as an adjunctive therapy.

Study Results

Commonly used plasma derivatives containing VWF and FVIII include Haemate P, which is considered the gold standard for preventing and treating bleeding events. The safety and efficacy of the product have been verified in numerous studies. Dobrkovska et al. demonstrated a good to excellent therapeutic response to the product in 99% of surgical procedures (n = 73) and 97% of bleeding episodes (n = 344) in a retrospective evaluation.

Lillicrap et al., in an extensive retrospective study organized by Canadian hemophilia centers, evaluated the efficacy of product administration based on ristocetin cofactor level. For the treatment of 437 bleeding episodes, a good to excellent clinical response was observed in 97% of total cases, 99% of surgical procedures, and 97% of bleeding episodes. Prophylactic administration showed a good to excellent clinical response in 100% of cases. No serious adverse events related to the treatment were observed in the study.

Recommended Perioperative Dosing

For patients unresponsive to desmopressin, the following doses of anticoagulant factors are recommended:

• For major surgical procedures, a minimum dose of 50 IU/kg RiCo activity VWF with repeated doses of 20–40 IU/kg every 8–24 hours to maintain specific activity of minimum plasma FVIII concentration > 50 IU/dl for at least 7–14 days is recommended.
• For minor surgical procedures, an initial dose of at least 30 IU/kg with repeated doses every 12–24 hours to maintain specific activity of minimum plasma FVIII concentration > 30 IU/dl for at least 5–7 days is recommended.
• For tooth extraction or traumatic or spontaneous bleeding, a single dose of 20–40 IU/kg is recommended.

Conclusion

The administration of anticoagulant factors represents an effective and safe modality for preventing and treating bleeding in patients undergoing surgical procedures or invasive examinations when desmopressin response is insufficient or when contraindicated.

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Sources:
1. Frederici A. B. Management of von Willebrand disease with factor VIII/von Willebrand factor concentrates: results from current studies and surveys. Blood Coagul Fibrinolysis 2005; 16 (Suppl. 1): S17–S21.
2. Dobrkovska A., Krzensk U., Chediak J. R. Pharmacokinetics, efficacy and safety of Humate-P in von Willebrand disease. Haemophilia 1998; 4 (Suppl. 3): 33–39, doi: 10.1046/j.1365-2516.1998.0040s3033.x.
3. Lillicrap D., Poon M. C., Walker I. et al.; Association of Hemophilia Clinic Directors of Canada. Efficacy and safety of the factor VIII/von Willebrand factor concentrate, haemate-P/humate-P: ristocetin cofactor unit dosing in patients with von Willebrand disease. Thromb Haemost 2002; 87 (2): 224–230.