Allergy, Anaphylaxis, TRALIJanejira Kittivorapart, MD.Department of Transfusion Medicine Faculty of Medicine Siriraj Hospital

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; 2011Vassallo R.Immunohematology 2004;20:226-33

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

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

3. Infusion of antibodies in donor plasma

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

Kay AB. Allergy and allergic disease s. New Eng J Med.2001;344(1):30-7

1. Immediate hypersensitivityRelease 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 exposureEdema, indurated swelling, blockage nose, wheezing lungs

Localized or confluent itching wheal & flare

Clinically diagnosis

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

Anaphylactic reactions Anaphylactic 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

Anaphylactoid Anaphylactoid reactionsreactions 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

Recipient’s plasma protein deficiency- IgA - Haptoglobin- Complement (C3, C4) - Transferrin- HLA antigens

Food allergens – peanut, glutenMedications Passive transfer of antibodies

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

Base on clinical signs & symptoms

SampsonH, J Allergy Clin Immunol.2006 Feb;117(2):391-7

Serum total tryptase

IgA level

Anti-IgA antibody

A protein component of human mast cell secretory granules

Two genes on chromosome 16p13.3 encoded for -tryptase and -tryptase

-tryptase would be negligible enzymatic activity

Mature -tryptase is retained in secretory granules until these cells are activated to degranulate

Selectively & abundantly produced by mast cells

Total tryptase = pro- and mature forms of /- tryptase

Schwartz LB.Immunol Allergy Clin N Am.2006;26:451-63

T1/2 of 1.5 – 2.5 hours

↑ - tryptase in anaphylaxis of sufficient severity

Inversely correlate with mean arterial pressure during anaphylactic shock

Schwartz LB.Immunol Allergy Clin N Am.2006;26:451-63Van der Linden Wf, Hack CE, et al.J Allergy Clin Immunol.1992;90:110-8

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Clotted blood 5 ml 1st time: 1-2 ช��วิโมิงหล�งเกั�ดอากัารสงส�ย anaphylaxis 2nd time: > 1 วิ�น หร"อ - 12 เด"อนหล�งมิ$อากัาร

(Baseline) Normal total tryptase levels 1 – 15 µg/L Method – Fluorescence Enzyme Immuno

Assay

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

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Clotted blood 3 – 5 ml น%าส&งภูายใน 6ช��วิโมิงหล�งเจาะเล"อด

Turn around time 5 วิ�น Nephelometer (BN Prospec)Minimum value: 1.24 mg/dl

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

Anti-IgA is detected in approximately one third of IgA-deficient individuals (28 – 37%) Class-specific antibodies Limited-specific antibodies

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 – dopamineAntihistamine Glucocorticoids

↓late-phase inflammatory responses

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 Hemaggluti

nation 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

TRALI was 1st reported in 1951 In 1970, it was postulated that

leukoagglutinins to HLA and non-HLA Ag were etiologic in TRALI reactions

51 years old male patientUnderlying disease: Cirrhosis, Child C Diagnosis – pyomyositis at left thighAdmit for intravenous antibiotics

Imaging study – soft tissue mass 22x6 cm Bleeding tumor at left thigh

Coagulopathy, DIC

Plan for drainage/biopsy

PRC FFP 500 ml

FFP 1000 ml

PRC

11 12 13 14 15 16 17 18 19 20

Furosemide

เหน"�อย

Off blood transfusion Intubation & respiratory supportDiuretics CXR Access central line no evidence of

volume overload

Normal CXR

Recipient’s HLA Ab – negative

FFP from 4 donors 2 from female donors

PRC from a male donor

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

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

Silliman C, Ambruso D, Boshkov.Blood.2005;105(6):2266-73

A case-control study: 2 patient groups were at risk for TRALI 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

Kleinman S, Caufield T, Chan P, et al. Transfusion. 2004

Bux J.Vox sang.2010;100:122-8

HLA & leukocyte Ab in donor plasma

Established the diagnosis

If positive

HLA & granulocyte Ag typing of the recipient

The International Granulocyte Immunology Workshops (IGIW) recommends to test both methods

The granulocyte immunofluorescence test (GIFT)

The granulocyte agglutination test (GAT)

Para formaldehyde-fixed PMNPFA fixation of cells before exposure

to human test sera eliminated intracellular fluorescence↓ non-specific membrane

fluorescence

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

The GAT is the most reliable technique for the detection of anti-HNA-3a

Requires viable cells, energy and an intact cytoskeleton

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

Monoclonal antibody immobilization of granulocyte antigens (MAIGA)

ELISATransfected cell linesLABScreen MultiWhite cell-IFT(WIFT)Five cell lineage

Respiratory supportNo role of diuretics and

corticosteroidsTRALI 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

Decreasing blood usageDisqualifiation of donors implicated

in TRALI reactions (AABB)“male- only plasma” (UK)

“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

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