VWF, ADAMTS13 and VWD

Question 1

Which factors do NOT affect VWF levels?
A. ABO blood group
B. Pregnancy
C. Diet
D. Stress
E. Inflammation

Answer 1

C. Diet

Question 2

What are the laboratory methods used to quantify VWF levels?
A. Measure VWF antigen levels
B. Measure VWF antibody levels
C. Measure circulating VWF levels

Answer 2

A. Measure VWF antigen levels
Using
Laurell rocket (immunoelectrophoresis)
ELISA
Immunoturbidimetric

Question 3

What are the methods used to measure VWF function?

Answer 3

A. Ristocetin cofactor assay (VWF: RCo)
B. Collagen binding assay (VWF: CB)
C. FVIII binding (VWF: VIIIB)
D. Ristocetin induced platelet agglutination (RIPA)

Question 4

How does VWF: RCo help measure VWF function?

Answer 4

Ristocetin A is a glycopeptide antibiotic from Norcardia lurida which binds to VWF and platelets. It alters the VWF configuration to expose the A1 binding site (GpIb). A1 binding site is responsible for binding to platelets via GpIb receptor. In normal VWF, the more RCo, the more functioning A1 exposed, the more binding to platelets and more agglutiation. This decreases the turbidity of mixture.
There is an excess of Ristocetin and dilutions of plasma.
In VWD, there may be a loss in functioning VWF leading to a decrease in decreased turbidity of mixture.

Question 5

Explain how Ristocetin induced platelet agglutination (RIPA) measures VWF function

Answer 5

In Type 2B (platelet type) VWD, there is a gain of function of VWF leading to increased affinity for platelet GpIb.
VWF binds to platelets without the necessary unravelling to expose A2 domain.
There is limited Ristocetin concentration and platelet-rich plasma

Question 6

Explain how FVIII binding (VWF: FVIIIB) measures VWF function

Answer 6

Used to diagnose Type 2N VWD where there is decreased affinity for FVIII.
Endogenous VWF bound to recombinant FVIII with
added substrate and colour generation.
In T2N VWD there’d be smaller % of VWF: FVIII complex

Question 7

Describe the pathophysiology of Type 2A VWD

Answer 7

Mostly autosomal dominant with loss of platelet-dependent function of VWF

Question 8

Describe the pathophysiology of Type 2B VWD

Answer 8

Mostly AD with increased affinity of VWF to GpIb receptors of platelets
Can lead to thrombocytopenia and loss of HMWM

Question 9

Describe the pathophysiology of Type 2M VWD

Answer 9

Mostly AD with reduced platelet-dependent function OR collagen-dependent function

Question 10

Describe the pathophysiology of Type 2N VWD

Answer 10

Mostly AD with decreased affinity for FVIII binding