von Willebrand disease


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Short review of vWD for medical student and resident

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von Willebrand disease

  1. 1. von WillebranddiseaseKaipol Takpradit
  2. 2. ● Introduction to von Willebrand factor● von Willebrand disease● ​Type of von Willebrand disease● ​Management of von Willebrand diseaseTopic
  3. 3. ● Named after Dr. Erik von Willebrand whodescribe hereditary bleeding disorderdistinguished from hemophilia in 1924● ​The protein was purified in 1970s● ​Produced in megakaryocyte, endothelium,subendothelial CNT● ​Size 250 kDa for monomer and up tomore than 20,000 kDa for multimervon Willebrand factor
  4. 4. ● Has functions of binding for platelet, FVIII,and collagen● Bind platelet to exposed collagen● Chaperone of FVIII● Cleaved by ADAMTS-13 protein at A2domain and eliminated by liver and spleenvon Willebrand factor
  5. 5. von Willebrand factorFVIII chaperonePlatelet GPIb bindingADAMTS-13 cleavage siteCollagen binding GPIIbIIIa binding
  6. 6. von Willebrand disease● Manifestation of platelet binding problem orseverely decrease FVIII half life● Present with mucocutaneous bleeding● Or hemophilia-like in type 2N and type 3● History of bleeding diathesis in first-degreerelatives● Significant bleeding may be determined bybleeding score of 3 in male and 5 in female
  7. 7. Bleeding scoreBowman M, et al. J Thromb Haemost. 2008:6(12);2062-66.
  8. 8. ●​Type 1: vary degree of decrease, vWF:Rco/vWF:Ag > 0.6●​Type 1 Vicenza: normal production andsecretion of vWF but has increaseexcretion●​A person with blood group O has lowervWF level than other ABO blood group​Type of von Willebrand disease
  9. 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 vWFType of von Willebrand disease
  10. 10. ●​The goal is to prevent bleeding●​Identify patients with increased bleedingrisk●​Patients with vWF level > 40 UI/dL orwithout history of bleeding are not at riskof bleeding●Desmopressin is the first line of treatmentManagement of vWD
  11. 11. Management of vWD●​Desmopressin infusion trial can determineresponse of the patient●If vWF:Rco/Ag near normal and level > 30UI/dL with low bleeding risk usuallyresponse to desmopressin●​For patients with type 2b or type 3 andpatients who do not respond todesmopressin factor replacement isrequired​
  12. 12. ●​Increase vWF secretion from endothelialWeibel-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 theresponse●​​Repeat at 12-24 hr up to 3-4 doses●​Tachyphylaxis after continuous dose●​Fluid pretension must be aware offDesmopressin infusion trial
  13. 13. Replacement therapy● vWF hemostat level 20-50%,half life 20-40hr● Use FVIII conc. that contain vWF 40-60 U/kgthen 40-50 U/kg q 12-24 hr up to 7 days● Cryoprecipitate 1 U/ 10 kg OD
  14. 14. Antifibrinolytic● Tranexamic acid may help in case of minorbleeding for hypermenorrhea● Dose 25 MKDose for oral and 10 MKDosefor IV 3-4 times/day● Renal impairment require dose reduction● Should be avoid in patient with highcardiovascular risk
  15. 15. For pregnancy● vWF usually increase in near-term period● Serial checking in the last trimester isrecommended● Desmopressin can be administered rightafter 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. 16. Inheritance● Autosomal Dominant● Except type 2n, 3 -> autosomal recessive
  17. 17. Question?FIN