Von Willebrands Disease

Question 1

VWD is synthesized in the ___ cells and ____. Storage granules in the endothelial cells known as the ____-___ bodies contain large VWF multimers. When released from storage, the VWF are “ultra large” and have the potential to stimulate significant clot formation. Instead, they are rapidly cleaved by protease _______ to the “normal sized” multimer required for normal hemostasis. Within platelets, VWF is stored in ___ ____.

Answer 1

VWD is synthesized in the ENDOTHELIAL cells and MEGAKARYOCYTES. Storage granules in the endothelial cells known as the WEIBEL-PALADE bodies contain large VWF multimers. When released from storage, the VWF are “ultra large” and have the potential to stimulate significant clot formation. Instead, they are rapidly cleaved by protease ADAMTS13 to the “normal sized” multimer required for normal hemostasis. Within platelets, VWF is stored in ALPHA GRANULES.

Question 2

within platelets, VWF is stored in ___ ___

within the endothelial cells, they are stored in ____-____ bodies.

Answer 2

within platelets, VWF is stored in ALPHA GRANULES

within the endothelial cells, they are stored in WEIBLE-PALADE bodies.

Question 3

2 functions of vwf

Answer 3

to form an adhesive bridge between platelets and vascular subenedothelial structures at sites of endothelial injury

carrier protein for factor VIII, which has a shortened half-life unless it is bound to VWF.

Question 4

most common inherited bleeding disorder

Answer 4

vonwillebrand factor disease.

Question 5

typical bleeding history in a patient with VWD

Answer 5

excessive mucocutaneous bleeding, life long easy bruising, menorrahia, bleeding following dental extractions etc.

Question 6

three types of inherited von willebrand disease

Answer 6

1; autosomal dominant disease– partial quantitative deficiency of vwf

2; autosomal dominant disease. Qualitative abrnormalities of vwf

3; autosomal recessive disorder; total deficiency of vwf, leads to severe disease with undetectable levels of vwf. more similar to hemophilia

Question 7

T/F people with vwf disease have a lower platelet count because of the bleeding.

Answer 7

false. usually have a normal platelet count. the platelets function fine, but the coagulation system itself is compromised because factor 8 of the intrinsic pathway cannot be stabilized.

Question 8

T/F VWF disease has a normal PT and elevated PTT

Answer 8

true– normal PT (because factor 8 does not affect the extrinsic pathway activity) but elevated PTT which measures the intrinsic pathway.

Question 9

how to diagnose vwd

Answer 9

measurement of the vwf antigen, vwf activity and factor 8 activity levels.

Question 10

how to tell the difference between types 1 ,2, 3 of vwd

Answer 10

type 1; autosomal dominant. has proportional reductions in vwf antigen, activity and factor 8 – quantitative deficiency

type 2. also autosomal dominant. QUALITATIVE DEFICIENCY. associated with vwf activity being lower than expected for the amount of antigen (not functioning properly). activity <30%

type 3. autosomal recessive. vwd undetectable or super low, also super low activity. factor 8<10% of normal.

Question 11

the most common medication to prevent and stop vwd bleeding

Answer 11

1. DDVAP/desmopressin.
   - promotes release of vwf from weibel-palade bodies. with this, vwf increases 3-5 fold.
2. replacement therapy with vwf concentrate
   - not super common because it involves IV plasma administration– choosing wisely recommends only if there’s they’re unresponsive to ddvap or for type 3, where ddvap doesn’t work.
3. antifibrinolytic drugs.
   - prevents dissolution of the hemostatic plug that is formed.
   - tranexamic

Question 12

tachyphylaxis

Answer 12

progressive decrease in response to diva because he body cannot replenish the vwf stores fast enough to keep up with the release stimulated by ddvap

Question 13

does VWF play a role in primary or secondary hemostasis?

Answer 13

plays role in primary hemostasis. binds to platelets and endothelial structures, forming an adhesive bridge between platelets and sub endothelial structures as well as between platelets themselves at the site of injury.

also helps with secondary hemostasis with final fibrin formation clotting cascade because its a carrier protein for factor 8, which has a shortened half life without vwf.

Question 14

t/f diva would help with type 3 vwd

Answer 14

false. ddvap helps promote vwf release from alpha granule and weibel-palade bodies, but won’t do anything if there’s no store at all.

Question 15

who would you give vwf/f8 concentrates to?

Answer 15

patients with type 3 vwd, or severe tapr 1 who do not respond to ddvap.
- typically used when other measures have failed, if prolonged treatment is required (post surgery), or prophylactically to prevent bleeding.

Question 16

name a common antifibrinolytic medication, and its contraindication

Answer 16

tranexamic. contraindicated in the presence of gross hematuria since clots may lead to ureteral obstruction.