Von Willebrand Factor Concentrate

Von Willebrand factor concentrate replaces von Willebrand factor in patients with von Willebrand disease who are unresponsive or unsuitable for desmopressin, or who need major surgery or have severe bleeding. Products are plasma-derived (von Willebrand factor with factor VIII) or recombinant (von Willebrand factor with little factor VIII).

Classification. Coagulation factor replacement.

Mechanism. Supplies von Willebrand factor, which mediates platelet adhesion at sites of vascular injury and carries and protects factor VIII.

Pharmacokinetics. One IU/kg of von Willebrand factor ristocetin cofactor activity raises plasma levels by about 1.5 to 2 IU/dL. Half-life is about 12 to 20 hours. Recombinant product contains little factor VIII, which rises endogenously over 6 to 24 hours.

Treatment of bleeding (doses in IU/kg of von Willebrand factor ristocetin cofactor).

• Minor or moderate bleed: 40 to 50 IU/kg, repeated every 8 to 24 hours for 2 to 3 days.
• Major bleed: 50 to 75 IU/kg, then 40 to 60 IU/kg every 8 to 12 hours for 3 days, then once or twice daily to 7 days.
• Maximum: 80 IU/kg for each dose; keep factor VIII under 150 IU/dL during repeated dosing of plasma-derived products.

Surgery. Major: before surgery, raise von Willebrand factor activity to 100 IU/dL and factor VIII to 80 to 100 IU/dL. Plasma-derived product 50 to 60 IU/kg; recombinant product 40 to 60 IU/kg, with factor VIII given 1 hour before if baseline is under 40 IU/dL. Maintain von Willebrand factor activity at 50 IU/dL or more for 3 to 7 days. Minor: 30 to 50 IU/kg.

Prophylaxis (frequent bleeding in type 3 and severe type 2). 40 to 60 IU/kg two to three times weekly, product-specific.

Adjustments. Kidney and liver: none. Children: same dose by weight, with attention to factor VIII. Pregnancy: levels fall rapidly in the first 3 weeks after delivery, so cover is continued for 3 weeks postpartum.

Contraindications. Known hypersensitivity; type 3 patients with alloantibodies need specialist cover because of anaphylaxis risk.

Adverse effects. Allergic reactions, headache, nausea, injection-site reactions, thrombosis (rare, linked to repeated high factor VIII), alloantibodies in type 3.

Interactions. Tranexamic acid is a useful adjunct for mucosal bleeding. Avoid combining with desmopressin in patients with type 2B disease because of platelet clumping and thrombocytopenia.

Pregnancy and breastfeeding. Used when needed.

Regional points. Concentrate is rarely available in East Africa; cryoprecipitate is the common fallback, with infection and volume risks. Diagnosis is often delayed; measure von Willebrand factor activity and antigen and factor VIII before treatment.

Common errors. Unmonitored repeated dosing of plasma-derived product causing very high factor VIII; no factor VIII cover with recombinant product in surgery; stopping cover too early after delivery.

Administration. Reconstitute as labelled and give by slow intravenous injection at no more than the labelled rate. Store as labelled.

Baseline. Von Willebrand factor antigen and activity, factor VIII, blood group, platelet count and function, subtype.

Monitoring. Von Willebrand factor activity and factor VIII (peak and trough) in surgery or major bleeding; keep factor VIII under 150 IU/dL. Bleeding diary.

Referral and escalation. Refer major bleeding, surgery and pregnancy to a haemophilia centre.