Why to Irradiate blood
Transfusion Associated Graft versus Host Disease
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(TAGVHD)Indications of Irradiated Components
Shelf Life of Irradiated products
Methods of Irradiation
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BackgroundFor Prevention of Transfusion Associated Graft versus
Host Disease (TAGvHD )
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Irradiation: induces DNA crosslinks, prevents (dividing)
lymphocyte proliferation
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Transfusion Associated Graft versus HostDisease (TAGvHD)
Delayed Immune transfusion reaction.
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Results from engraftment of foreign T cells.Clinically similar to Graft versus Host Disease (GvHD)
except pancytopenia is a prominent feature.
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Usually arises 3 to 30 days after transfusion.Onset of symptoms occur early with signs and
symptoms of bone marrow aplasia.
Factors for developing TA GvHD
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Predisposing conditions-
HLA antigen difference between donor & recipient
Presence of donor immunocompetent cells in blood
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component
A recipient incapable of rejecting donor immunocompetent
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cellsThe number of lymphocytes in a bag is determined by the age
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of the blood component and the irradiation status.
Fresher blood components contain more viable T lymphocytes.
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Pathophysiology
Immuno-compromised host ?
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Congenital/Acquired- lack the ability to reject
the donor T cells
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Immuno-competent host ? When donor isHomozygous and recipient is heterozygous for
HLA haplotype (sp Class I) ? Host does not
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recognize donor lymphocytes as foreign
Uneventful Transfusion
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Uneventful Transfusion
Host is Immuno-compromised
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Host is Immuno-compromised
Host is Immuno-competent
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Directed Donation ( One way HLA match)-
Most Common
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Recipients of fresh blood with lot of viable T-lymphocytes ( granulocytes, fresh whole
blood)
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Cardiac bypass surgery ( In Japan)
Host is Immuno-competent
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Host is Immuno-competent
Host is Immuno-competent
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Host is Immuno-competent
Clinical Presentation
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Signs and symptoms usually begin 3-30 daysafter transfusion.
Initially fever with skin manifestations
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Gastro Intestinal manifestationsHepatic dysfunction
BM failure with pancytopenia
Death often occurs with infection or bleeding
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manifestationsSkin Manifestations
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Erythematous maculopapularrash
Pruritic
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Involves palms and soles andspreads throughout the body
Blisters and ulcers - in severe
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cases.
GIT - Manifestations
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Diarrhoea ? secretory, voluminous (>2L/day)Bleeding - life threatening intestinal
hemorrhage.
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Nausea, vomiting.Anorexia
Abdominal pain
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LiverJaundice and hepatomegaly
Mainly cholestatic hepatitis
? lymphocytic infiltration of portal tracts
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? damage to bile duct epithelium? consequent destruction of bile ducts.
Increased liver enzymes
Increased serum billirubin
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DiagnosisTA-GVHD is probably underdiagnosed since it may be
wrongly attributed to
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- Intercurrent infection
- Severe drug reaction
- Auto immune diseases
Histopathological/hematological features and
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detection of donor lymphocytes or DNA (mixed
chimerism)
Diagnostic testing
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Skin biopsy
superficial perivascular lymphocyte infiltrate
necrotic keratinocytes
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bullae formationBone marrow examination
Hypocel ular/aplastic marrow
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Only macrophages presentLiver biopsy
Smal bile duct degeneration & eosinophilic necrosis
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Intense periportal inflammationLymphocytic infiltration
Definitive diagnosis-
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Identification of donor derived lymphocytes in recipientcirculation/tissues+ presence of clinical symptoms
Differential diagnosis
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Acute viral hepatitis
Severe drug reaction
Dengue fever and leptospirosis
Acute sero-conversion illness due to HIV
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infection
Prognosis
Fatality
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Profound marrow aplasiaMortality>90%(1-3weeks)
Management of Suspected/proven
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diseaseMust be treated in a specialized unit
High dose steroids ?First line - antilymphocyte and
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antiinflammatory activityMethotrexate & Cyclosporine-A ? to prevent the disease
Steroid refractory GvHD
? Anti-thymocyte globulin (ATG)
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? Azathioprine? Intravenous immunoglobulins
Supportive therapy ? Antibiotics
Stem cell transplantation
Prevention
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Prevention is better than cure
Gamma Irradiation of cellular Blood
component
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- 25Gy- centre of blood bag
- 15Gy-peripheral part of blood bag
Photochemical treatment of platelets &
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plasmaWhen to Irradiate
At a minimum, cellular components shall be irradiated
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when:
1.A patient is identified as being at risk for TAGVHD
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2.The donor of the component is a blood relative of therecipient
3.The donor is selected for HLA compatability, by typing or
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crossmatching.
AABB Technical Manual
Clinical Indications for Irradiated Components
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Well-documented indications
? Intrauterine transfusions
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? Premature, low-birthweight infants? Newborns with erythroblastosis fetalis
? Congenital immunodeficiencies
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? Hematologic malignancies or solid tumors (neuroblastoma,
sarcoma, Hodgkin disease)
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? Components that are crossmatched, HLA matched, ordirected donations
? Fludarabine therapy
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? Granulocyte components
Potential indications
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? Other malignancies, including those treated withcytotoxic agents
? Donor-recipient pairs from genetically homogenous
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populations
Usual y not indicated
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? Patients with human immunodeficiency virus? Term infants
? Non-immunosuppressed patients
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General aspects about Irradiation of Blood
components
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Lymphocyte viability is retained in stored red cel s for at
least 3 weeks
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TA-GvHD has been reported after transfusion of wholeblood, red cel s, platelets and granulocytes
TA-GvHD has not been described fol owing transfusion
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- frozen deglycerolized red cells, which are thoroughly washedfree of leucocytes after thawing.
- cryoprecipitate
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- fresh frozen plasma or- fractionated plasma products
Shelf Life of Irradiated Products
Irradiated Red Blood Cel s
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Red cells can be irradiated up to 14 d after collection
and stored for at least a further 14 d without
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significant loss of viabilityShortened to 28 days after irradiation or until original
expiration date, whichever comes first
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Where the patient is at particular risk from
hyperkalaemia, e.g. intrauterine or neonatal
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exchange transfusion, it is recommended that redcells be transfused within 24 h of irradiation or that
the cells are washed.
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Platelets
No effect of Gamma irradiation below 50 Gy on
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platelet functionPlatelets can be irradiated at any stage during storage
and can thereafter be stored up to their normal shelf
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life after collection.
Granulocytes
The evidence for irradiation damage to granulocyte
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function is conflicting
But in any case granulocyte products should be
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transfused as soon as possible after irradiationAll granulocytes should be irradiated before issue and
transfused with minimum delay.
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Methods for Irradiation
Gamma Irradiators
X-ray Irradiators
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(Gamma rays and X-rays are similar in their ability to
inactivate T lymphocytes in blood components at a given
absorbed dose)
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Gamma IrradiatorsBoth cesium and cobalt irradiators are available
Expensive
Disposal present significant difficulties
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These highly radioactive cores may present a security riskin hospital settings
As the source decays, regular recalibration is required and
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irradiation time progressively increases
Strict regulatory requirements are required
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Cel IrradiatorX-ray Irradiators
Less Expensive
Absence of a radioactive source
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Fewer regulatory requirementsEffective Dose of Radiation
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Dose to the center of the irradiation field must be at
least 25 Gy
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Minimum delivered dose delivered to any other portionmust be 15 Gy
No more than 50 Gy should be delivered to the product.
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Special labels (radiochromic film labels which changecolor upon being irradiated) are affixed to units to
confirm irradiation of an adequate dosage
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Process takes 5minutes.
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Cons of Irradiated ProductsReduced shelf life 35->28 days
Leakage of potassium
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Theoretical risks
?Malignant change? Reactivation of latent virus?
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Plastic leakage?Practical issues
?Cost/upkeep/validation/security of irradiators
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Non-irradiation Prevention Strategies?
Leukocyte reduction has been shown to
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reduce the risk of TAGVHD, especially in agenetically diverse population, but is not a
substitute for irradiation in at-risk populations.
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Psoralen (S59) + ultra-violet A ? used for
pathogen inactivation
Conclusions
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Prevention is only the key for this deadly disease.
Al donor blood and blood products for immuno
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compromised, suspected or potential y immuno-compromised patients should be irradiated.
As new potent immunosupressive drugs and biological
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agents are introduced into practice, there is a need forregular review of recommendations regarding irradiated
blood components.
References
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1. Transfusion-Associated Graft-VersusHost Disease in Severe Combined
Immunodeficiency; S Sebnem Kilic, S Kavurt,S Balaban Adim: J Investig
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Allergol Clin Immunol2010; Vol. 20(2): 153-1562. Transfusion-associated graft-versus-host disease; D. M. Dwyre & P. V.
Holland :Vox Sanguinis, 2008 95;85?93
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3. Treleaven, J., Gennery, A., Marsh, J., Norfolk, D., Page, L., Parker, A., Saran,
F., Thurston, J. and Webb, D. (2011), Guidelines on the use of irradiated
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blood components prepared by the British Committee for Standards inHaematology blood transfusion task force. British Journal of Haematology,
152: 35?51. doi:10.1111/j.1365-2141.2010.08444.x
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4. Review - Transfusion-associated graft-versus-host disease, BJH
2002;117:275?287
References
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5. Denise M. Harmening. Modern Blood Banking & Transfusion Practices. 6thEdition.
6. http://www.bbguy.org/education/videos/whyirradiate/
7. Rossi's Principles of Transfusion Medicine
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8. TA-GvHD management guidelines ?NHSThankYou