Short review of vWD for medical student and resident

1. von Willebrand
disease
Kaipol Takpradit

2. ● Introduction to von Willebrand factor
● von Willebrand disease
● ​Type of von Willebrand disease
● ​Management of von Willebrand disease
Topic

3. ● Named after Dr. Erik von Willebrand who
describe hereditary bleeding disorder
distinguished from hemophilia in 1924
● ​The protein was purified in 1970s
● ​Produced in megakaryocyte, endothelium,
subendothelial CNT
● ​Size 250 kDa for monomer and up to
more than 20,000 kDa for multimer
von Willebrand factor

4. ● Has functions of binding for platelet, FVIII,
and collagen
● Bind platelet to exposed collagen
● Chaperone of FVIII
● 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
● Manifestation of platelet binding problem or
severely decrease FVIII half life
● Present with mucocutaneous bleeding
● Or hemophilia-like in type 2N and type 3
● History of bleeding diathesis in first-degree
relatives
● Significant bleeding may be determined by
bleeding score of 3 in male and 5 in female

7. Bleeding score
Bowman M, et al. J Thromb Haemost. 2008:6(12);2062-66.

8. ●​Type 1: vary degree of decrease, vWF:
Rco/vWF:Ag > 0.6
●​Type 1 Vicenza: normal production and
secretion of vWF but has increase
excretion
●​A person with blood group O has lower
vWF level than other ABO blood group​
Type of von Willebrand disease

9. ●​Type 2: abnormal function
○ ​ 2A: decreased larger multimer, vWF:
Rco/vWF:Ag < 0.6
○ ​2B: increase affinity to platelet, hyper-
response to RIPA
○ ​2M: decrease affinity to platelet GPIb
○ ​2N: decrease affinity to FVIII, FVIII:
c/vWF:Ag< 0.5
●​Type 3: severe or totally absence of vWF
Type of von Willebrand disease

10. ●​The goal is to prevent bleeding
●​Identify patients with increased bleeding
risk
●​Patients with vWF level > 40 UI/dL or
without history of bleeding are not at risk
of bleeding
●Desmopressin is the first line of treatment
Management of vWD

11. Management of vWD
●​Desmopressin infusion trial can determine
response of the patient
●If vWF:Rco/Ag near normal and level > 30
UI/dL with low bleeding risk usually
response to desmopressin
●​For patients with type 2b or type 3 and
patients who do not respond to
desmopressin factor replacement is
required​

12. ●​Increase vWF secretion from endothelial
Weibel-Palade bodies or from platelet α-
granule
●Dose 0.3 mcg/kg IV or SC
●​150-300 mcg intranasal
●​Check for level at 1 and 4 hr to access the
response
●​​Repeat at 12-24 hr up to 3-4 doses
●​Tachyphylaxis after continuous dose
●​Fluid pretension must be aware off
Desmopressin infusion trial

13. Replacement therapy
● vWF hemostat level 20-50%,half life 20-40
hr
● Use FVIII conc. that contain vWF 40-60 U/kg
then 40-50 U/kg q 12-24 hr up to 7 days
● Cryoprecipitate 1 U/ 10 kg OD

14. Antifibrinolytic
● Tranexamic acid may help in case of minor
bleeding for hypermenorrhea
● Dose 25 MKDose for oral and 10 MKDose
for IV 3-4 times/day
● Renal impairment require dose reduction
● Should be avoid in patient with high
cardiovascular risk

15. For pregnancy
● vWF usually increase in near-term period
● Serial checking in the last trimester is
recommended
● Desmopressin can be administered right
after an umbilical cord is cut
● Replacement immediately (40-50 U/kg)
before delivery and at 24 and 72 hr later (20-
30 U/kg)
● Antifibrinolytic can relieve excessive lochia

16. Inheritance
● Autosomal Dominant
● Except type 2n, 3 -> autosomal recessive

17. Question?
FIN