VWF

Question 1

What is VWF?

Answer 1

Protein made in endothelial cells and in megakaryocytes

Question 2

Where is VWF stored?

Answer 2

Alpha granules of platelets

Question 3

Where is VWF made?

Answer 3

ER

Question 4

How are VWF multimers made?

Answer 4

Disulphide bonds added at tubulation & dimerization generate multimers

Question 5

What is VWF processing influenced by?

Answer 5

Elongational forces in flowing blood

Question 6

What does elongational forces support?

Answer 6

enhances cleavage by ADAMTS13
facilitates platelet binding

Question 7

What four things does VWF interact with upon release?

Answer 7

Platelets
Clotting factors
Leukocytes
Collagen

Question 8

What does WPB exocytosis place on endothelial surfaces?

Answer 8

P-selectin

Question 9

What is P-selectin?

Answer 9

receptor for leukocytes -> decelerates them -> allows them to roll on vessel surface

Question 10

How does VWF bind to platelets?

Answer 10

VWF binds to collagen
Gets stuck
VWF is pulled by shear force of blood flow
Becomes unfolded at A1 domain
Platelets binding sites are exposed
Platelets can now bind via GPIb

Question 11

What is VWF release stimulated by?

Answer 11

ADH and epinpehrine

Question 12

What clotting factor does VWF bind to?

Answer 12

Factor VIII -> protects its degradation

Question 13

What domain does VWF bind to collagen at?

Answer 13

A3

Question 14

What domain do platelets bind via GPIb?

Answer 14

A1

Question 15

What is VWD?

Answer 15

Hereditary bleeding disorder that affects function of VWF (3 types)

Question 16

What are characteristics of type 1 VWD?

Answer 16

Partial quantitative deficiency (70%)
reduced FVIII & platelet function
autosomal dominant trait

Question 17

What are characteristics of type 2 VWD?

Answer 17

Qualitative deficiency (25%)
increased ADAMTS13-mediated proteolysis (2A)
increased binding to GPIb on platelets ->increased removal of platelet aggregates (2B)
impaired platelets binding (2M)
impaired factor VIII binding (2N)

Question 18

What are characteristics of type 3 VWD?

Answer 18

total deficiency (5%)

Question 19

What is ristocetin?

Answer 19

Drug that artificially unfolds VWF -> induces platelet aggregation

Question 20

How is type 1 VWD treated?

Answer 20

Stimulation of VWF release using vasopressin or desmopressin

Question 21

How is type 2 and 3 VWD treated?

Answer 21

Administration of VWF and/or factor VIII

Question 22

What is an example of indirect treatment?

Answer 22

anti-fibrinolytic agents which binds plasmin preventing interaction with fibrin