2. โ Introduction to von Willebrand factor
โ von Willebrand disease
โ โType of von Willebrand disease
โ โManagement of von Willebrand disease
Topic
3. โ Named after Dr. Erik von Willebrand who
describe hereditary bleeding disorder
distinguished from hemophilia in 1924
โ โThe protein was purified in 1970s
โ โProduced in megakaryocyte, endothelium,
subendothelial CNT
โ โSize 250 kDa for monomer and up to
more than 20,000 kDa for multimer
von Willebrand factor
4. โ Has functions of binding for platelet, FVIII,
and collagen
โ Bind platelet to exposed collagen
โ Chaperone of FVIII
โ Cleaved by ADAMTS-13 protein at A2
domain and eliminated by liver and spleen
von Willebrand factor
5. von Willebrand factor
FVIII chaperone
Platelet GPIb binding
ADAMTS-13 cleavage site
Collagen binding GPIIbIIIa binding
6. von Willebrand disease
โ Manifestation of platelet binding problem or
severely decrease FVIII half life
โ Present with mucocutaneous bleeding
โ Or hemophilia-like in type 2N and type 3
โ History of bleeding diathesis in first-degree
relatives
โ Significant bleeding may be determined by
bleeding score of 3 in male and 5 in female
8. โโType 1: vary degree of decrease, vWF:
Rco/vWF:Ag > 0.6
โโType 1 Vicenza: normal production and
secretion of vWF but has increase
excretion
โโA person with blood group O has lower
vWF level than other ABO blood groupโ
Type of von Willebrand disease
9. โโType 2: abnormal function
โ โ 2A: decreased larger multimer, vWF:
Rco/vWF:Ag < 0.6
โ โ2B: increase affinity to platelet, hyper-
response to RIPA
โ โ2M: decrease affinity to platelet GPIb
โ โ2N: decrease affinity to FVIII, FVIII:
c/vWF:Ag< 0.5
โโType 3: severe or totally absence of vWF
Type of von Willebrand disease
10. โโThe goal is to prevent bleeding
โโIdentify patients with increased bleeding
risk
โโPatients with vWF level > 40 UI/dL or
without history of bleeding are not at risk
of bleeding
โDesmopressin is the first line of treatment
Management of vWD
11. Management of vWD
โโDesmopressin infusion trial can determine
response of the patient
โIf vWF:Rco/Ag near normal and level > 30
UI/dL with low bleeding risk usually
response to desmopressin
โโFor patients with type 2b or type 3 and
patients who do not respond to
desmopressin factor replacement is
requiredโ
12. โโIncrease vWF secretion from endothelial
Weibel-Palade bodies or from platelet ฮฑ-
granule
โDose 0.3 mcg/kg IV or SC
โโ150-300 mcg intranasal
โโCheck for level at 1 and 4 hr to access the
response
โโโRepeat at 12-24 hr up to 3-4 doses
โโTachyphylaxis after continuous dose
โโFluid pretension must be aware off
Desmopressin infusion trial
13. Replacement therapy
โ vWF hemostat level 20-50%,half life 20-40
hr
โ Use FVIII conc. that contain vWF 40-60 U/kg
then 40-50 U/kg q 12-24 hr up to 7 days
โ Cryoprecipitate 1 U/ 10 kg OD
14. Antifibrinolytic
โ Tranexamic acid may help in case of minor
bleeding for hypermenorrhea
โ Dose 25 MKDose for oral and 10 MKDose
for IV 3-4 times/day
โ Renal impairment require dose reduction
โ Should be avoid in patient with high
cardiovascular risk
15. For pregnancy
โ vWF usually increase in near-term period
โ Serial checking in the last trimester is
recommended
โ Desmopressin can be administered right
after an umbilical cord is cut
โ Replacement immediately (40-50 U/kg)
before delivery and at 24 and 72 hr later (20-
30 U/kg)
โ Antifibrinolytic can relieve excessive lochia