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Introduction

Inhibitor in VWD Dr Bijan Keikhaei Professor of Pediatric Hematology and Oncology Research Center for Thalassemia and Hemoglobinopathy, Health Institute, Ahvaz Jundishapur University of Medical Sciences. Introduction.

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Introduction

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  1. Inhibitor in VWDDr Bijan Keikhaei Professor of Pediatric Hematology and OncologyResearch Center for Thalassemia and Hemoglobinopathy, Health Institute, Ahvaz Jundishapur University of Medical Sciences

  2. Introduction • In 1974, Sarji et al first reported a case of an alloantibody against VWF in a multitransfused patient. This was followed quickly by additional reports from Sweden and Italy.

  3. Introduction The development of alloantibodies against VWF represents a rare but serious complication of treatment of VWD, occurring in ∼5% to 1o% of type 3VWD patients.

  4. Introduction In 1984, a cross-sectional study was published describing the results of a survey of severe VWD in Western Europe and Israel, with all laboratory results confirmed in a centralized laboratory. One hundred and six patients were included from 21 countries; of those, 8 were found to have alloantibodies, resulting in a prevalence of 7.5%.

  5. Introduction Type 3 VWD is the least common and most severe among the three types of VWD. The incidence was estimated at 3-5/million and the severity is thought to be similar to mild or moderate hemophilia A.

  6. CLINICAL MANIFESTATION Affected patients can present with a range of symptoms, including lack or loss of hemostaticresponse to infused VWF concentrates up to anaphylactic reactions in rare cases.

  7. Risk Factor for Inhibitor Development • A previous exposure to VWF , • extent of the exposure. • Partial or complete VWF gene deletions. • Positive family history of anti-VWF antibodies .

  8. Anti-VWF Antibodies Anti-VWF antibodies are mostly characterized as polyclonal IgG class alloantibodies . Target specificity has been demonstrated towards the GP1b-bindingA1 and the collagen binding A3 domain of VWF in selected cases . Some antibodies have been reported to partially inhibit factor VIII coagulation activity (FVIII:C).

  9. Comparison of Inhibitor in Hemophilia and VWD

  10. Case scenario A 26-year-old woman was previously diagnosed with type 3 VWD in Shafa hospital in AJUMS. Blood and Factor analysis revealed Hb11.5g/dl,RBC:6,MCV:65,MCH:19.1,Blood Group:A+, PTT:75sec,BT:>20min,VWF Ag:4%,VWRCo:3%,VIII-C:3% . She had received cryoprecipitate and tranexamic acid at the time of diagnosis after adenoidectomy at 3 yr-old. She was taken occasional Haemate-p and tranexamic acid for gum bleeding and menorrhagia.

  11. Case scenario The patient showed allergic reaction in response to the administration of two vials of Haemate-p at 21 –yr-old. The allergic reaction marked by an breathless feeling, dropped blood pressure and cold extremities. The allergic reaction responded to the administration of epinephrine, Hydrocortisone and antihistamine. The bleeding ceased by Tranexamic acid. With the impression of Inhibitor development the patient’s blood was taken for CBC,BT,PTT,MIXED PTT,VWF Ag,VWF-Rco,VIII-C ,VWF Ab,VIII Ab.

  12. Case scenario Hb:9.5,RBC:5.5,MCV:52,MCH:18,RDW:24,Ferritin:10 BT:>20,PTT:75,Mixed PTT:55,VWF-Ag:2%,VWF-Rco:2%,VIII-C:2% VWF Ab:40 BU VIII Ab:1.5 BU

  13. Case scenario She got married at the age of 25. She is pregnant and candidate for cesarean section. What treatment should be administrated for the patient?

  14. Treatment Recombinant FVIII has been used successfully for hemostatic therapy in patients with anti-VWF antibodies. The resultant plasma FVIII half-life can be expected to be short (<2 hours), because of the lack of stabilization by VWF, but by using higher doses given by continuous infusion, use of rFVIII alternating with rFVIIa. platelet infusions

  15. Summary The frequency of alloantibody in VWD is 5-10%. Most alloantibodies occur in VWD Type3 The source of alloantigen in producing alloantibody is: -cryoprecipitate -PD-VWF -rVWF Alloantibody is IgG sub-class.

  16. Summary • Alloantibodies inhibitor show two different clinical courses: • -refractory to vwf concentrate replacement. • severe anaphylactic shock • Treatment is rVIII,alternating with rVII,platelet

  17. Thank You for your Attention

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