Von Willebrand Disease Flashcards
What are the factors that affect vwf level?
ABO blood group - o has the lowest vwf
age, stress, exercise, pregnancy, OCP/HRT, thyroid disease, venepuncture and inflammation
What tests are used to assess the vwf level and its functions?
Vwf antigen is used to quantify the vwf to test the function: ristocetin cofactor assays collagen binding assay FVIII binding multimeric structure ristocetin induced platelet aggregation
What are the abnormalities of vwd…?
Type 2A: Abnormality in the A2 domain which leads to exposure of the scissile cleavage bond in the globular conformation
Type 2B: there is increased platelet binding which leads to increased tethering and inappropriate unravelling of VWF
There is also a 2M - decreased platelet dependent function
2N - decreased affinity for binding to fviii
What is the basis of vwd inheritance? 2A
2A - autosomal dominant
can be due to enhanced ADAMTS13 mediated proteolysis - loss of large multimers or retention of vwf in er, defects in formation
CK domain
What are the main treatments available for vwd?
DDAVP
VWF replacement
Adjunctive therapy - antifibrinolytics - tranexamic acid/mirena coil
How does collagen-binding activity work?
Vwf is allowed to bind to a layer of collagen
an ELISA is then completed with anti-vwf antibody, this sows the amount that is bound to collagen
How is Factor VIII binding capacity of vwf tested?
FVIII is removed from vwd, then is readded and elisa done to look at how much fviii is bound
What is the basis of inheritance for 2M?
platelet/collagen dependent function lost
autosomal dominant
mutations in a1 domain fo a3
A1/A3
inheritence for 2b?
autosomal dominant
spontaneous platelet interaction in vivo
A1
Inheritance for 2n?
autosomal recessive
loss of FVIII binding function
mutations on FVIII binding site of vwf - D’ -D3
T3 inheritance?
Autosomal recessive - heterozygous null mutations do not cause significant bleeding
How is the ristocetin cofactor assay completed? What is ristocetin?
Ristocetin is an antibiotic which unravels vwf
Excessive ristocetin and platelets are added to a sample of vwf, as the vwf unravels platelets should bind giving a rate of agglutination
How does the RIPA test work?
A low dose of ristocetin is added, not enough for normal platelets to bind
this is a test for vwd 2B as there is excessive interactions with platelets in this disease
How does the vwf antigen assay work?
latex microbeads coated with anti-vwf are added and binding increases the optical density and this is compared with known values
The value is the compared with the function expected for that level
What is the multimeric structure test used for, what does it show?
It is used to identify the multimeric size and quantity of each size
