Von Willebrand Disease (vWD) is caused by qualitative and quantitative deficiencies in von Willebrand factor. It is characterised by mucocutaneous haemorrhage.
Subtypes of von Willebrand Disease
| Subtype | Description |
|---|---|
| Type 1 von Willebrand disease (75%) | Autosomal dominant quantitative defect of vWF. May have low levels of factor VII. Presents with mild to moderate bleeding following haemoastatic challenge (e.g., surgery and dental procedures), and menorrhagia in women. |
| Type 2 von Willebrand disease (20%) | Qualitative defect of vWF. Type 2A is the most common form. Type 2B has a shortage of both vWF and platelets. |
| Type 3 von Willebrand disease (1 – 5%) | Autosomal recessive inheritance with virtually complete deficiency of vWF. It may present with more serious bleeding, e.g. haemarthrosis and gastrointestinal bleeding. |
| Acquired von Willebrand syndrome | Due to underlying conditions that affect the function of vWF, e.g., lymphoproliferative and myeloproliferative diseases, malignancy, and autoimmune conditions |
- Sites of synthesis of vWF
- Cytoplasmic Weibel-Palade bodies of endothelial cells
- Alpha granules of platelets
- Functions of vWF
- Platelet adhesion
- Platelet aggregation
- Carries factor VIII in its inactive form, preventing it from being degraded
- Pathophysiology
- Release of vWF in response to haemostatic
- Qualitative and quantitative defect of vwf → decreased binding of platelet Gp1B/IX/X and GpIIa/IIIa at shear stress → platelet-type bleeding
- Qualitative and quantitative defects of vWF → rapid proteolysis of factor VIII → impaired complex with IXa and activation of Xa in the intrinsic factor → coagulpathy
- Signs and symptoms
- Menorrhagia in women
- May lead to iron deficiency anaemia
- Epistaxis
- Frequent and prolonged
- Excessive bruising
- Prolonged bleeding post-surgery
- Bleeding gums
- Haemarthrosis and gastrointestinal bleeding in type 3 von Willebrand disease
- Menorrhagia in women
- Differentials
- Purpura simplex
- Medication-induced cagulopathy
- Liver cirrhosis
- Malignancy with bone marrow involvement
- Haemophilia
- Disseminated intravascular coagulopathy
- Investigations
- Complete blood cunt
- Normal
- Thrombocytopaenia may be present in type 2B von Willebrand disease
- aPTT
- Normal or prolonged if factor VIII is sufficiently reduced (vWF carries factor VIII)
- PT
- Normal
- Firbinogen
- Normal
- Factor VIII assay
- Normal or decreased
- vWF antigen (Ag)
- Low
- Undetectable in type 3
- vWF activity by measuring ristocetin cofactor (RCo) and collagen binding (CB) as ratios of vWF antigen levels
- RCo/Ag and CB/Ag > 0.6 in type 1
- RCo/Ag or CB/Ag < 0.6 in type 2
- Complete blood cunt
- Treatment
- Inform the doctor or dentists before procedures that may cause bleeding
- Avoid aspirin, NSAIDs and anticoagulants unless prescribed
- Desmopressin is first-line
- Stimulates the release of vWF from Weibel-Palade bodies
- Tranexamic acid and desmopressin for bleeding episodes
- Can be used as prophylaxis before surgery
- vWF-FVIII concentrate for patients who do not respond to desmopressin
- Can also be used as prophylaxis before surgery
- Hormonal management and intrauterine device for menorrhagia