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חסר IgA ומתן מרכיבי דם

חסר IgA ומתן מרכיבי דם. דר' ורד יהלום ס' מנהלת שירותי הדם. IgA Deficiency (IgAD). Selective IgAD most common primary immunodeficiency Western World Average 1:700 1: 168 (Spain), 1:18,500 (Japan) IgA < 5-7 mg/dL (individuals > 4 years old) 80% develop symptoms within 20 years

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חסר IgA ומתן מרכיבי דם

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  1. חסר IgA ומתן מרכיבי דם דר' ורד יהלום ס' מנהלת שירותי הדם

  2. IgA Deficiency (IgAD) • Selective IgAD most common primary immunodeficiency Western World Average 1:700 1: 168 (Spain), 1:18,500 (Japan) • IgA < 5-7 mg/dL (individuals > 4 years old) • 80% develop symptoms within 20 years • Sinopulmunary infections, autoimmune disorders, allergies, GI disease, Gut & Lymphoid malignancies • 20% IgG subclass deficiency (IgG2/IgG4) • IgA subclass deficiency – low/normal IgA level lack IgA subclass (A1/A2) or allotype [IgA2M(1), IgA2M(2)] • Severe/Absolute/Total IgAD < 0.0016 – 0.05 mg/dL • IgAD blood donor < 0.05 mg/dL

  3. IgA quantitation Highly sensitive immunoassays limited to specialized laboratories – none in Israel

  4. Anaphylactic Transfusion Reaction • Incidence: ??? 1:20,000 – 1:60,000 Canada- 1.3 /106 blood products – Severe IgA anaphylaxis • Pathophysiology: Immediate generalized reaction IgE mediated,C3a, C4a, C5a, Tryptase, Cytokines, Leukotrienes, PAF • Signs & Symptoms • Circulatory – Hypotension to cardiac arrest • Pulmonary – laryngospasm, Bronchospasm, respiratory distress, • Gastrointestinal • Cutaneous AngioedemaUrticaria (0.4-1%) IgE + Histamine mediatedPruritus

  5. Severe Anaphylactic Transfusion reaction - DD • TRALI • TACO • Hemolytic Transfusion Reaction • Bacterial contamination • Underlying condition • Coincident clinical conditions (PE) • Infusion biological mediators • Administration of antigens to which the recipient is presensitized (medications, food, chemicals, atopens) • Transfer of donor IgE - Ab against substances in the recipient (Haptoglobin, α1-antitrypsin,Transferrin, Albumin) - Rare • Preformed anti- IgA (>75% reports prior to TRALI era - 1985)

  6. Anaphylactic Transfusion Reaction • Laboratory testing • Rule out other potential causes • IgA quantitative – Pre transfusion sample • Anti-IgA –usually anti-IgG (IgM/?IgE) • Therapeutic/Prophylactic Approach • Stop Transfusion • Trendelenburg & Fluids • Oxygen • Epinephrine, antihistamine, corticosteroids, ß2 agonists • IgA-deficient blood components WHICH PRODUCTS &TO WHOM ?

  7. Are anti-IgA Clinically relevant ? • 28-100% IgAD develop anti-IgA Isolated <combined < + RA < +SLE • * Sandler et al, 359 individuals major allergic reaction 18.1% had class specific anti-IgAIf IgA < 0.05mg/dL – 76.3% • ARC - 1978-1995, 395 cases suspected IgA anaphylaxis – 17.5 % anti-IgA • * 0.7% patients – limited specificity anti-IgA ??? Clinical significance Urticarial but not anaphylactic reactions * Blood 1994; 84 (9): 2031-5

  8. Are anti- IgA Clinically relevant ? • * UK – 1:30,000 - major allergic reaction 1:2700 - IgAD + anti- IgA 1~100 - IgAD + anti- IgA - reaction • Predictive value of anti-IgA for anaphylactic reaction is low • Major allergic reactions often associated high titer (>1:1000) IgG class specific Ab • ?? What defines the pathogenicity of the antibody • ??? Recommendations regarding safe transfusion of IgA containing plasma products * Munks R, Booth JR, Sokol RJ: Immunohamatology 1998; 14:155-60

  9. Available IgAD products • Washed RBC’s (x 2-5 liter)Deglycerolized RBC’s • Washed PLT’s • Plasma/ RBC/PLT IgAD donors (<0.05mg/dL)- RARE • IgA depleted IVIG (Gammagard S/D IGIV 5%, Baxter)

  10. Criteria for IgADblood donors • IgA < 0.05 mg/dLmeasured X2, High sensitivity assays • Some exclude IgAD + anti-IgA

  11. IgAD donor panel -MDA * 1 donor – Total IgAD,All Others < LOD testing laboratory, none tested for anti-IgA

  12. How do wetransfuseIgAD patient? • No evidence based clinical protocols • No guidelines • Practices vary widely

  13. How do I treat IgAD patient? • Just had anaphylactic/toid reaction – Tx requiredIdeally – Rapid IgA test/ anti-IgA IgA detected – Exclusion IgA mediated anaphylaxis Unit/donor related causeTransfuse carefully regular components, monitorIf screening unavailable/ IgA decreased (not absolute IgAD) Careful controlled Tx of regular componentsWashed RBC’s, PLT’sAttempt to obtain IgAD blood components – Limited availability Time for allocation Misuse of scarce resourceSolvent Detergent (S/D) treated plasmaIf Tx urgent – History equivocalTansfuse conventional blood products, monitor carefully Sandler SG: Transfusion 2006;(46) 10-13

  14. How do I treat IgAD patient? • History of Severe “ anaphylactic” reaction No further details available- Tx not urgentTest IgA – if not recently transfused If IgAD & unconfirmed anti- IgA Washed RBC’s, PLT’sIgAD Blood components • History of Severe “ anaphylactic” reaction, confirmed IgAD (+/- anti-IgA)IgAD Blood componentsIgA depleted IVIG Sandler SG: Transfusion 2006;(46) 10-13

  15. “New” technology for IgAD & anti-IgA * Transfusion 2008;48: 2057-9

  16. New technology for IgAD & anti-IgA • * Brown et report evaluation of Particle gel immunoassay ID –PaGIA (DiaMed AG) to detect IgAD & anti- IgA 24 samples previously tested • Correlation standard methods (Nephelometry & Hemaglutination) 6/6 – Severe IgAD +High titer anti-IgA 16/18 – negative, anti-IgA titer < 1:128 significance low titers?1 sample IgA< 0.067 mg/dL not detected • Advantages – Simple & readily available technology Fast screening (20 min) Inexpensive (? Cost) Reassurance IgAD products not available Better rare resource allocation * Transfusion 2008;48: 2057-9

  17. How can you help? • Refer IgAD for plasma donation (WB, Apheresis) • Test patients with history of anaphylaxis for IgA If IgA < LOD, confirm sensitive test Test for anti-IgA (ARC) Refer for donation • Test family members of IgAD • Notification / Tag identification

  18. Unresolved issues • Which investigations should be preformed in IgAD patients? • Should patients be monitored over the years? • Should we test IgA & anti-IgA in all patients about to receive blood components? • Which IgA Ab should we test for? • Should IgA titers be monitored? • What is the clinical relevance of IgA titer? • Should all IgAD & anti-IgA be given IgAD components? • Is the use of IgA depleted IVIG justified in all IgAD patients?

  19. תודות • לכל התורמים חסרי IgA שתורמים למאגר הנדיר ומסכימים שיעשה שימוש בפלסמה הנדירה שלהם • ד"ר ורוניקה גנדלמן • עובדי שירותי הדם מד"א • ד"ר מנחם רותם – יו"ר החברה הישראלית לאלרגיה ואימונולוגיה קלינית • לכם – על ההקשבה

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