Von Willebrand disease is caused by mutations in the von Willebrand factor gene and results in bleeding problems. There are several types of von Willebrand disease characterized by differences in von Willebrand factor amount and function. Treatment depends on disease severity and involves desmopressin, factor replacement therapy, or antifibrinolytics to prevent and control bleeding.

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