Von Willebrands Disease

Question 1

Definition

Answer 1

Most common inherited bleeding disorder due to either quantitative or qualitative abnormality of VWF
= decreased endothelial collagen attachment, platelet adhesion, and binding + carrying of factor VIII.

Question 2

Aetiology : Types of Von Willebrands Disease

Answer 2

Inherited:
Type 1 - Autosomal dominant
Type 2 - bad quality = A, B, M, N
Type 3 - Autosomal recessive = MOST SEVERE
Acquired:
Normal genes but present with symptoms
Background condition: SLE, meds: Ciprofloxacin

Question 3

Normal physiology

Answer 3

Synthesised + endothelial cells + megakayrocytes
Synthesis regulated by gene on short arm of chromosome 12
1. Injury
2. Histamine + thrombin stimulate endothelial cells + megakaryocytes to secrete VWF
3. VWF attaches to exposed collagen fibres in injured BV wall = acts as glue for platelet receptors GP1b = mesh
4. Fibrin fibres deposit form clot
Also binds and carries factor VIII = involved in coagulation cascade of intrinsic pathway = prevent early degradation from protein C + S.

Question 4

Risk factors

Answer 4

Family history
Consanguineous relationships
Lymphoproliferative disorders
Aortic stenosis
Myeloproliferative disorders
Hypothyroidism

Question 5

Signs and symptoms

Answer 5

Bleeding from mucosa
- epistaxis (nose bleeds)
- menorrhagia
- bruising
- gum bleeding
Can be severe if on: anticoagulation, anti platelets (aspirin), NSAIDS: celecoxib
Severe bleeding in joints, muscle, and GI

Question 6

Diagnosis

Answer 6

NORMAL PROTHROMBIN TIME
INCREASED ACTIVATED PARTIAL THROMBOPLASTIN
Decreased VWF
Normal F8/9 assays

Question 7

Treatment

Answer 7

Non curable
Desmopressin = increased release of VWF from endothelial WEIBEL-PALADE BODIES
Severe: exogenous VWF