Von Willebrand Disease

From Ganfyd

A congenital bleeding disorder due to deficiency in von Willebrand factor.

Aetiology

von Willebrand factor is a protein with 2 major functions:

1. binds platelets in plug formation
2. carrier for Factor VIII

Deficiency is usually autosomal dominant. Subtypes are:

• Type 1 - simple deficiency. Commonest, mildest subtype.
• Type 2 - mutant protein. In Type 2b, platelet binding is unregulated, causing thrombocytopenia in addition to bleeding disorder.
• Type 3 - total absence. Severe, very rare. Factor VIII levels are very low (3-5% of normal).

Clinical presentation

Variable, usually mucosal bleeding eg nose bleeds, ecchymoses. VWF levels vary with age, stress and other factors. Hence bleeding during an acute illness eg ruptured appendix may be essentially normal, whereas elective dental extraction may result in severe bleeding. Women tend to present earlier as menorrhagia is a common symptom.

Haematomas are not often seen, compared with haemophilia. Petechiae are not usually seen, except in Type 2b disease where there is thrombocytopenia. Use of NSAIDs however may cause petechiae.

Diagnosis

Bleeding time is not particularly sensitive or specific. Prothrombin time is normal. APTT may be prolonged, depending on the impact on factor VIII.

Ristocetin stimulates platelet aggregation in presence of vWF so is a more sensitive and specific test.

Treatment

Minor bleeding may be treated with:

• Desmopressin (DDAVP) - increases vWF levels 2-5x. Can be given by intranasal route or intravenously. Not the same dose/preparation as for enuresis! Responsiveness is pretty consistent over time and within families. Side effects are headache and flushing (slow down infusion), else seizures (related to hyponatraemia).
• Tranexamic acid - antifibrinolytic, useful for mucosal bleeding. Given orally, or topically eg mouthwash.

For major bleeding, or for covering surgery, various vWF concentrates exist with different ratios of vWF and Factor VIII that can be given iv. These increase levels maximally within 30-60 minutes so should be given close to time of procedure. Ideally, vWF levels should be at least 40% normal, which may require 2-3 days of infusions. Cryopreciptate was used before these preparations became available.

Also consider:

• Platelet count, esp in type 2b.
• Factor VIII level, esp in severe types. Give factor concentrate as for haemophilia.
• Tachyphylaxis - phenomenon of reduced effectiveness with repeated doses.