Von Willebrand's disease

Question 1

Define Von Willebrand’s disease.

Answer 1

Bleeding disorder which may be present with mucocutaneous bleeding (mouth, epistaxis, menorrhagia), increased bleeding after minor trauma or easy bruising.

Behaves like a platelet disorder.

Question 2

How common is vWD? Who is usually affected?

Answer 2

Most common hereditary coagulopathy

1-2% affected

More common in females

More severe with blood type O

Question 3

What is the aetiology of Von Willebrand’s disease?

Answer 3

Abnormalities in expression or function of vWF (factor)

Usually autosomal dominant OR occasionally recessive OR acquired

Question 4

What are the types of Von Willebrand’s Disease?

Answer 4

vWD is a bleeding disorder due to:

• Type 1:reduced levels of normal vWF (AD)-60-80%
• Type 2: defective vWF (AD) - 20-30%
• Type 3: complete lack of vWF and highly reduced factor 8 (AR) - rare

Question 5

What is von Willebrand factor and what are its functions?(2)

Answer 5

vWF is plasma glycoprotein involved in bloof clotting -

1. acts as adhesive bridge between platelet receptos (GP-Ib) and damaged subendothelium collagen IV of vessels
2. also binds to factor VIII and prevents its degradation

Question 6

Where is vWF made and where is it stored?

Answer 6

It is made in the endothelium and stored in Weibel-Palade bodies.

Question 7

How does vWD present?

Answer 7

Varies according to degree of deficiency:

• Bleeding tendency from mucosa e.g. bleeding post tooth extraction
• Spontaneous bleeding (internal or joints)
• Blood clots during childbirth
• Death
• Type 3 is more severe and can cause bleeding into joints and soft tissues.

Question 8

How does VWD compare to haemophilias?

Answer 8

The bleeding is more superficial compared to haemophilias

Question 9

What investigations would you do for vWD?

Answer 9

Clotting profile - prolonged bleeding time, prolonged APTT, N PT

FBC - normal platelets

Factor VIII - reduced

vWF levels - reduced

Ristocetin cofactor assay - reduced platelet aggregation by vWF in the presence of ristocetin

Plasma levels of vWF - keep in mind that deficiency can be quantitative or qualitative:

• Quantitative deficiency - detected by vWF antigen assay.
• Qualitative deficiency - detected by a number of methods including glycoprotein binding assay, ristocetin cofactor activity, ristocetin-induced platelet agglutination

Question 10

How do you manage vWD?

Answer 10

1. Avoid NSAIDs
2. Give DDAVP
3. Tranexamic acid (fibrinolytic inhibitor) for mild bleeding and in minor surgery
4. Factor VIII concentrate (containing FVIII and vWF) or specific vWF may be another option

Question 11

How is type 3 vWD inherited?

Answer 11

Autosomal recessive

Question 12

What is the prognosis with vWD?

Answer 12

May require intermittent treatment for active bleeding but respond well to treatment each time