Von Willebrand Disease

Question 1

What’s the role of vWF?

Answer 1

• contributes to forming 1 haemostatic plug
  > sticks to collagen (subendothelial) & multimers elongates exposing its binding sites for plts to bind onto (glycoprotein 1b-V-IX)

Question 2

Pathophysiology of VWD (disease)

Answer 2

• ## quantitative / qualitative abnormality of vWF (low # vWF OR dysfunctional vWF)

Question 3

whats the risk factr (like dx): if Patient with an appropriate bleeding history and VWF
activity 0.30–0.50 iu/ml (N: 0.40 - 2.40 iu/ml)

Answer 3

primary haemostatic bleeding with reduced VWF

Question 4

• Males and females inherit mutant alleles (of VWD) with [a] frequency
• However, clinical signs more common in [b]

Answer 4

a) equal
b) females (2F:1M)

Question 5

whats the clinical signs (symptoms) that would make you want to Ix if its VWD
*some clinical signs similar to plt disorders

Answer 5

• excessive bleeding after dentral extraction etc.
• Epistaxis (nose bleed) & menorrhagia (excess period bleeding)
• easy bruising

Question 6

What is measured in the initial Ix of VWD (determine primary classification)

Answer 6

• FVIII
• VWF:Ag (quantity)
• VWF activity to bind to both GpIb & Collagen

Question 7

What are the 3 primary classification of VWD (T1-3)

Answer 7

T1: partial deficiency of VWF (function normal)
T2: Poorly functioning VWF
T3: Complete deficiency of VWF

Question 8

What is meassured at the secondary classification of VWD (2-3)

Answer 8

• Multimer analysis (electrophorhesis)
• Plt aggregometry: Ristocetin (cofactor) induced plt agglutinatioin > ability for vWF to agglutinate plt
• (vWF- FVIII binding assay)

Question 9

What are the 4 secondary classification of Type 2 VWD (T2A, B, M, N)*****.

Answer 9

• T2A: loss/dec of HMW multimers (dec plt adhesion)
• T2B: inc VWF binding => loss of lrg VWF multimers (converted to sml pieces by ADAMTS13) & can cover plts (dysfunctional = thrombocytpenia)
• T2M: dysfunctional plt adhesion to GPIb or collagen (but normal HMW multimer)
• T2N: impaired FVIII binding site on VWF (can be mistaken for mild Haem A)

Question 10

the molecular pathology underlying VWD

Answer 10

Many exons mutated in VWF gene
e.g. large deletions = inhibit

Question 11

What is plt-type VWD (PT-VWD)

Answer 11

• pseudo VWD
• mutation in GP1Ba gene => excessive binding of GPIba (plt) & VWF => removal of HMW VWF multimers & plt (similar to Type 2B)

Question 12

Lab features of PT-VWD

Answer 12

• vary lvls of thrombocytopenia
• loss of HMW VWF multimers
• VWF:RCo/VWF:Ag ratio <0.6
• enhanced ristocetin-induced plt aggregation (RIPA)

Question 13

PT-VWD & Type 2B present similar features (loss of VWF multimers) but how can you differentiate b/w the 2 (tests)

Answer 13

• Cryop.ppt. challenge: Add of Cryo. (has VWF) to pt w/ PT-VWD = aggregate spontaneously
• Genetic analysis
• Flow cyto: assess VWF binding to plt w/ Ristoc.

Question 14

What is acquired VWD

Answer 14

• dec [VWF], not by mutation
• 40+ yo w/ no bleeding history
• usually result from range of disorders e.g. AI disorders, drugs