von Willebrand disease

Question 1

T/F: vWD is the most common inherited bleeding diathesis overall.

Answer 1

True

-Hemophilia A is considered the most common cause of SEVERE hemophila

Question 2

vWD is a simultaneous impairment of the coagulation cascade and platelet function.

• Coagulation effect?
• Platelet function effect?

Answer 2

• vWF maintains high levels of circulating factor 8 (VIII)

- vWF is operant in the formation of platelet thrombi

Question 3

Where does synthesis of vWF occur? (2)

Answer 3

• Endothelial cells

- Megakaryocytes

Question 4

Where in endothelial cells is vWF stored?

Answer 4

Weibel-Palade bodies

Question 5

Where in megakaryocytes is vWF stored?

Answer 5

alpha granules

Question 6

vWF is secreted by endothelial cells into underlying basement membrane. What happens when the basement is exposed?

Answer 6

vWF is bound by platelet GPIb

Question 7

How is GPIb activated?

• In vivo
• In vitro

Answer 7

• In vivo - shear stress
• In vitro - Ristocetin

*vWF is also referred to as ristocetin cofactor

Question 8

vWF is also secreted into circulation, what breaks it down?

Answer 8

ADAMTS-13

-variably sized multimers, most commonly dimers

Question 9

What does vWF do in circulation?

Answer 9

Complexes with F8 (VIII) and protects it from degradation

*vWF is sometimes called F8 related antigen

Question 10

What is the most common type of vWD?

-Second MC

Answer 10

Type I (70%)
-Type IIa (10-15%)

Question 11

Type I vWD severity?

Answer 11

Mild QUANTITATIVE defect

Question 12

Type I vWD lab findings:

• Platelet count
• PT
• aPTT
• Bleeding time
• PFA-100

Answer 12

Type I vWD lab findings:

• Platelet count - Normal
• PT - Normal
• aPTT - Prolonged
• Bleeding time - Prolonged
• PFA-100 - Prolonged

Question 13

What are the levels in Type I vWD?

• Factor 8
• vWF Ag
• vWF activity

Answer 13

• Factor 8 - Decreased
• vWF antigen - Decreased
• vWF activity - Decreased

*Ratio of vWF activity to vWF antigen approaches 1 (always >0.7)

Question 14

Type IIa vWD severity?

Answer 14

Moderate to severe bleeding

Question 15

Type IIa vWD mutation.

Answer 15

vWF gene on exon 28

-Missense mutation

Question 16

What is the abnormality in Type IIa vWD?

Answer 16

Absence of large multimers (abnormal multimer pattern)

Prolonged aPTT

Question 17

What are the levels in Type IIa vWD?

• Factor 8
• vWF Ag
• vWF activity

Answer 17

• Factor 8 - Normal/-
• vWF Ag - Normal/-
• vWF activity - Decreased (Markedly; <50%)

Question 18

What is the ratio of vWF antigen to vWF activity in Type IIa vWD?

Answer 18

<0.7

Question 19

Type I vWD:

• Multimer pattern
• Genetics

Answer 19

• Normal

- Unknown genetics

Question 20

Type IIb vWD mutation.

Answer 20

Gain-of-Function mutation in GPIb binding domain of vWF

Question 21

What is the abnormality in type IIb vWD?

Answer 21

Decreased large multimers

Question 22

How is Type IIb vWD unique? (3)

Answer 22

• Enhanced Ristocetin induced platelet aggregation
• DDAVP causes profound thrombocytopenia and bleeding
• Spontaneous binding of vWF to platelets

Question 23

What must Type IIb vWD be distinguished from?

Answer 23

Platelet type vWD

Question 24

what is the mutation in Platelet type vWD?

Answer 24

Gain of function mutation in the gene that encodes he platelet GPIb receptor

Question 25

What are the characteristic lab features for Type IIb and Platelet type vWD?

Answer 25

- Thrombocytopenia - Decreased HMW Multimers *Enchanced binding is selective for HMW multimers and results in clearance of both platelets and HMW multimers from the blood

Question 26

Type IIM vWD is caused by what? | -What does this prevent

Answer 26

Loss of Function in GPIb binding domain | -Prevents binding of vWF to GPIb

Question 27

How can you distinguish between Type IIa/IIb from IIm vWD?

Answer 27

Type IIM multimer analysis appears normal | *Type IIa/IIb have Decreased Large multimers

Question 28

Type IIN (Normandy) vWD is caused by what?

Answer 28

Mutation in the domain that binds factor VIII (8)

Question 29

``` Type IIN (Normandy) vWD lab findings. -What does this mimic? ```

Answer 29

Decreased circulating F8 -Mimics Hemophilia A *distinguished by autosomal inheritance pattern

Question 30

what is the vWF quantity and function in Type IIN vWD?

Answer 30

vWF quanitity and function are unaffected

Question 31

What is the most severe type of vWD?

Answer 31

Type III vWD | -virtually NO vWF

Question 32

What genetics in Type III vWD?

Answer 32

Frameshift mutations, Nonsense mutations, and Deletions in the vWF gene

Question 33

What are the laboratory findings in Type III vWD? - Factor 8 - vWF Ag - vWF activity - Multimers

Answer 33

- Factor 8 - Low - vWF Ag - Low - vWF activity - Low - Multimers - All sizes decreased/absent

Question 34

What type of vWD is caused by an abnormal GPIb, leading to increased avidity for vWF?

Answer 34

Pseudo or Platelet type vWD

Question 35

What ABO blood group has slightly lower vWF levels?

Answer 35

Type O

Question 36

T/F: Newborns have high vWF activity.

Answer 36

True | -Disease may not be detectable until 1 y/o

Question 37

What is the Ristocetin cofactor assay (vWF activity assay)?

Answer 37

- Pt plasma is added to formalin fixed normal platelets in the presence of Ristocetin - Plasma deficient in vWF does not fully aggregate *normal plasma will cause platelet agglutination

Question 38

What is the gold standard for classification of vWD?

Answer 38

Gel Electrophoresis

Question 39

In surgical and acute bleed settings, what is he best monitoring test for patient with vWD?

Answer 39

Factor 8 activity