Investigation of transfusion reactions

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  • NO is believed to play major role in cardiovascular collapse
  • Vegf – vascular endothelial growth factor
  • GIFT: Paraformaldehyde-fixed PMNs are incubated with serum or plasma to allow PMN reactive Abs to bind to the antigenic epitopes  then washed and incubated with a reagent blend of fluorescence-labelled F(ab’)2 anti-human IgG, IgM and IgA (FITC-AHG)  analyzed by flow cytometry or by fluorescence microscopy.
  • PMN reactive IgG Abs bind to native antigens on unfixed PMNs, sensitizing the cells (2) Sensitized PMNs undergo chemotaxis & move toward other PMNs to form microscopic agglutinates which are viewed and graded microscopically
  • Investigation of transfusion reactions

    1. 1. Allergy, Anaphylaxis,TRALI Janejira Kittivorapart, MD. Department of Transfusion Medicine Faculty of Medicine Siriraj Hospital
    2. 2.  Allergic reaction : 1 – 3 /100 transfusions  Anaphylaxis :  1.7 – 4.3 /100,000 RBC & plasma transfusions  62.6 /100,000 platelets pools Roback J. Technical Manual. 17th ed.Bethesda(MD):AABB; 2011 Vassallo R.Immunohematology 2004;20:226-33
    3. 3.  Recipient IgE or non – IgE antibodies to proteins or other allergenic soluble substances in the donor plasma  Release of mast-cell mediators  Histamine, tryptase, leukotrienes, prostaglandins and platelet-activating factor
    4. 4. 1. Histamine generate from recipient’s mast cells and basophils 2. Histamine leakage into plasma during storage  ↑ reactions if ↑ storage time  Allergy of their own autologous products 1. Infusion of antibodies in donor plasma
    5. 5.  Retrospective single center review of all transfusion reaction  1991-1996  20 from 967 reactions (2.1%) from autologous units  4 from 20 were allergic reactions Domen RE.Transfusion.1998;38(3):296-300
    6. 6. Kay AB. Allergy and allergic disease s. New Eng J Med.2001;344(1):30-7
    7. 7. 1. Immediate hypersensitivity Release of mast-cell mediators Smooth muscles contraction, vasodilatation, ↑vascular permeability, hyper secretion of mucus 2. Late-phase reaction Peak at 6-9 hours after allergen exposure Edema, indurated swelling, blockage nose, wheezing lungs
    8. 8.  Localized or confluent itching wheal & flare  Clinically diagnosis
    9. 9.  First generation H1-blocking antihistamine  Combining H1 and H2 antagonists – better results in non-transfusion settings  Hold the transfused unit  Re-transfusion can be resumed in mild urticaria after all the lesions has cleared
    10. 10. Anaphylactic reactionsAnaphylactic reactions  Allergen in plasma  patient who previous sensitization has an IgE directed against that allergen  Histamine, leukotrienes, prostaglandins, PAF  Platelet-activating factor: induce production of “Nitric oxide” (NO)  NO as a potent vasodilator
    11. 11. Anaphylactoid reactionsAnaphylactoid reactions  Clinically identical to anaphylaxis  Mechanisms that do not involve IgE  Complement fixation and generation of anaphylatoxins : C3a, C4a, C5a  Cytokines secreted by monocytes  Activation of basophils and mast cells
    12. 12.  Recipient’s plasma protein deficiency - IgA - Haptoglobin - Complement (C3, C4) - Transferrin - HLA antigens  Food allergens – peanut, gluten  Medications  Passive transfer of antibodies
    13. 13.  6 yr old boy with ALL  Received LPPC  Developed rash, angioedema, hypotension  Tryptase 24 µg/L (<5 µg/L)  History of previous severe allergy to peanuts  Donors eating handful of peanuts shortly before donation  The digestion-resistant peptide from Ara h2 can be detected in serum for up to 24 hours after ingestion Jacobs J.N Eng J Med.2011;364(20):1981-2
    14. 14.  Base on clinical signs & symptoms SampsonH, J Allergy Clin Immunol.2006 Feb;117(2):391- 7
    15. 15.  Serum total tryptase  IgA level  Anti-IgA antibody
    16. 16.  A protein component of human mast cell secretory granules  Two genes on chromosome 16p13.3 encoded for α-tryptase and β-tryptase  α-tryptase would be negligible enzymatic activity  Mature β-tryptase is retained in secretory granules until these cells are activated to degranulate
    17. 17.  Selectively & abundantly produced by mast cells  Total tryptase = pro- and mature forms of α/β- tryptase Schwartz LB.Immunol Allergy Clin N Am.2006;26:451-
    18. 18.  T1/2 of 1.5 – 2.5 hours  ↑ β- tryptase in anaphylaxis of sufficient severity  Inversely correlate with mean arterial pressure during anaphylactic shock Schwartz LB.Immunol Allergy Clin N Am.2006;26:451-63 Van der Linden Wf, Hack CE, et al.J Allergy Clin Immunol.1992;90:110-8
    19. 19.  สาขาวิชาโรคภูมิแพ้และวิทยาภูมิคุ้มกัน ภาควิชา กุมารเวชศาสตร์  Clotted blood 5 ml  1st time: 1-2 ชั่วโมงหลังเกิดอาการสงสัย anaphylaxis  2nd time: > 1 วัน หรือ 1-2 เดือนหลังมีอาการ (Baseline)  Normal total tryptase levels 1 – 15 µg/L  Method – Fluorescence Enzyme Immuno Assay
    20. 20.  IgA deficiency: IgA level < 7 mg/dl (in age > 4 years old)  Donor IgA deficiency: IgA level < 0.05 mg/dl  Incidence of IgA deficiency varies with population studied and limitation of screening test  US 1: 328  Australia 1: 442  Japan 1: 18500
    21. 21.  ภาควิชาวิทยาภูมิคุ้มกัน  Clotted blood 3 – 5 ml นำาส่งภายใน 6 ชั่วโมง หลังเจาะเลือด  Turn around time 5 วัน  Nephelometer (BN Prospec)  Minimum value: 1.24 mg/dl
    22. 22.  Measure the light scattered through the sample at an angle from the incident beam  Compare results to the light-exiting dilutions of IgA standards  Determining the rate of change of light scattering rather than static value
    23. 23.  Anti-IgA is detected in approximately one third of IgA-deficient individuals (28 – 37%)  Class-specific antibodies  Limited-specific antibodies
    24. 24.  1:1000 epinephrine(1 mg/ml) IM 0.2-0.5 ml for adults (0.01 ml/kg in children) q 15 - 30 minutes as needed  Vigorous IV crystalloid  Pressors – dopamine  Antihistamine  Glucocorticoids  ↓late-phase inflammatory responses
    25. 25.  Remove plasma proteins;  IgA concentration in washed red blood cells  “6-washed” No. of wash cycles Total vol. of NSS used (L) Observed IgA content (mg/dL) Results of Hemagglutinat ion inhibition assay 3 1.0 0.11-0.27 Positive 4 1.3 0.01-0.04 Weakly positive 6 2.0 0.00 Negative
    26. 26.  TRALI was 1st reported in 1951  In 1970, it was postulated that leukoagglutinins to HLA and non-HLA Ag were etiologic in TRALI reactions
    27. 27.  51 years old male patient  Underlying disease: Cirrhosis, Child C  Diagnosis – pyomyositis at left thigh  Admit for intravenous antibiotics  Imaging study – soft tissue mass 22x6 cm Bleeding tumor at left thigh Coagulopathy, DIC
    28. 28.  Plan for drainage/biopsy PRC FFP 500 ml FFP 1000 ml PRC 11 12 13 14 15 16 17 18 19 20 Furosemide เหนื่ อย
    29. 29.  Off blood transfusion  Intubation & respiratory support  Diuretics  CXR  Access central line  no evidence of volume overload
    30. 30. Normal CXR
    31. 31.  Recipient’s HLA Ab – negative  FFP from 4 donors  2 from female donors  PRC from a male donor
    32. 32. Feature TRALI TACO Temperature Fever can be present Unchanged BP Hypotension Hypertension Respiratory symptoms Acute dyspnea Neck veins Unchanged Can be distended Auscultation Rales Rales, S3 may be present Chest radiograph Diffuse, bilateral infiltrates Ejection fraction Normal, decreased Decreased PA occlusion pressure ≤ 18 mmHg > 18 mmHg Fluid balance +/- + Response to diuretic Minimal Significant BNP < 200 pg/ml >1200 pg/ml Leukocyte antibodies Donor leukocyte antibodies +, crossmatch incompatibility between donor and recipient Donor leukocyte Ab ± If +, suggestion of TRALI
    33. 33.  Immunocompetent host  Single event  Two events model  Neutropenic patient  Infusion of Infusion of vascular endothelial growth factor (VEGF), an effective permeability factor or  Infusion of antibodies against HLA class II antigens Silliman C, Ambruso D, Boshkov.Blood.2005;105(6):2266-73
    34. 34. Silliman C, Ambruso D, Boshkov.Blood.2005;105(6):2266-73
    35. 35.  A case-control study: 2 patient groups were at risk forTRALI  In the induction phase of hematologic malignancies (p < 0.0004)  Cardiovascular disease who required bypass surgery (p < 0.0006) Silliman CC, et al. Blood.2003;101:454-62
    36. 36. Kleinman S, Caufield T, Chan P, et al. Transfusion. 2004
    37. 37. Bux J.Vox sang.2010;100:122-8
    38. 38. HLA & leukocyte Ab in donor plasma Established the diagnosis If positive HLA & granulocyte Ag typing of the recipient
    39. 39.  The International Granulocyte Immunology Workshops (IGIW) recommends to test both methods  The granulocyte immunofluorescence test (GIFT)  The granulocyte agglutination test (GAT)
    40. 40.  Para formaldehyde-fixed PMN  PFA fixation of cells before exposure to human test sera eliminated intracellular fluorescence ↓ non-specific membrane fluorescence
    41. 41. 1) PMN reactive antibodies bind to native antigens on unfixed PMNs, sensitizing the cells 2) Sensitized PMNs undergo chemotaxis & move towards other PMNs to form agglutinates
    42. 42.  The GAT is the most reliable technique for the detection of anti-HNA-3a  Requires viable cells, energy and an intact cytoskeleton
    43. 43.  Both the GIFT & GAT can detect antibodies to HLA on PMNs  Routinely taken to differentiate HLA from HNA antibodies  Testing samples with & without platelet absorption
    44. 44.  Monoclonal antibody immobilization of granulocyte antigens (MAIGA)  ELISA  Transfected cell lines  LABScreen Multi  White cell-IFT(WIFT)  Five cell lineage
    45. 45.  Respiratory support  No role of diuretics and corticosteroids  TRALI reactions should be reported to the blood supplier  To ascertain information about the donor of the transfused blood components  To allow the quarantine or recall of additional components from the donor
    46. 46.  Decreasing blood usage  Disqualifiation of donors implicated in TRALI reactions (AABB)  “male- only plasma” (UK)
    47. 47.  “male- only plasma”  High plasma-volume components from female donors ▪ Could be used if they were selected to minimize their risk of HLA or HNA alloimmunization ▪ Nulliparous donors ▪ Female donors with negative HLA/HNA antibody testing
    48. 48. Thank You

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