Haematology - Von Willebrand Disease Flashcards
Definition
Hereditary bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor (vWF) = a clotting protein for platelet adhesion and aggregation.
What is vWF role in body
Produced in endothelial cells and megakaryocytes . vWF acts as a cofactor for platelet adhesion by binding to Gp1b and causing platelet activation.
VWF also serves as a carrier for factor VIII , another essential clotting protein, and its deficiency can additionally cause a mild form of haemophilia.
Types of VWD
Type 1: Partial quantitative deficiency of VWF (heterozygous patients = 80% )
Type 2: Qualitative deficiency with four subtypes (2A, 2B, 2M, 2N)
Type 3: severe or total quantitative defect, which arises through an autosomal recessive pattern
Epidemiology
MC inherited bleeding disorder
FHx
Women
Blood type O
Signs
Petechiae < 4mm bleed into the skin
Purpura: 4-10mm bleed into the skin
Ecchymosis: > 10mm bleed into the skin
Symptoms
Epistaxis
Menorrhagia
Prolonged bleeding after surgery or dental procedures
Diagnosis
Exclude alternative diagnoses:
- FBC,
- PT (extrinsic clotting pathways)
aPTT: Intrinsic clotting pathway = prolonged due to an associated factor VIII deficiency
vWF antigen level
GOLD STANDARD: vWF activity levels = for qualitative deficiencies:
- vWF factor <0.3iu/ml is diagnostic
- vWF factor 0.3-0.5iu/ml with bleeding is also diagnostic
Factor VIII activity: given the role of VWF as a carrier for factor VIII, there is increased degradation of this factor in VWD
Treatment
FIRST LINE: Desmopressin = stimulates release of stored VWF from endothelial cells via cAMP-mediated mechanism
- if unresponsive to FL + type 3 VWD = IV VWF
Avoid anti-platelets and NSAIDS
Complication
Severe or life-threatening haemorrhage: particularly postoperatively or after head trauma
Haemarthrosis : this describes bleeding into the joints, which can lead to joint damage over time
