Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st Year, 2nd Year, 3rd Year and Final year Transfusion Medicine and Blood Bank 5 Irradiation Of Blood Components PPT-Powerpoint Presentations and lecture notes
Irradiation of Blood and Blood
Components
Contents
Why to Irradiate blood
Transfusion Associated Graft versus Host Disease
(TAGVHD)
Indications of Irradiated Components
Shelf Life of Irradiated products
Methods of Irradiation
Background
For Prevention of Transfusion Associated Graft versus
Host Disease (TAGvHD )
Irradiation: induces DNA crosslinks, prevents (dividing)
lymphocyte proliferation
Transfusion Associated Graft versus Host
Disease (TAGvHD)
Delayed Immune transfusion reaction.
Results from engraftment of foreign T cells.
Clinically similar to Graft versus Host Disease (GvHD)
except pancytopenia is a prominent feature.
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
Predisposing conditions-
HLA antigen difference between donor & recipient
Presence of donor immunocompetent cells in blood
component
A recipient incapable of rejecting donor immunocompetent
cells
The number of lymphocytes in a bag is determined by the age
of the blood component and the irradiation status.
Fresher blood components contain more viable T lymphocytes.
Pathophysiology
Immuno-compromised host ?
Congenital/Acquired- lack the ability to reject
the donor T cells
Immuno-competent host ? When donor is
Homozygous and recipient is heterozygous for
HLA haplotype (sp Class I) ? Host does not
recognize donor lymphocytes as foreign
Uneventful Transfusion
Uneventful Transfusion
Host is Immuno-compromised
Host is Immuno-compromised
Host is Immuno-competent
Directed Donation ( One way HLA match)-
Most Common
Recipients of fresh blood with lot of viable T-
lymphocytes ( granulocytes, fresh whole
blood)
Cardiac bypass surgery ( In Japan)
Host is Immuno-competent
Host is Immuno-competent
Host is Immuno-competent
Host is Immuno-competent
Clinical Presentation
Signs and symptoms usually begin 3-30 days
after transfusion.
Initially fever with skin manifestations
Gastro Intestinal manifestations
Hepatic dysfunction
BM failure with pancytopenia
Death often occurs with infection or bleeding
manifestations
Skin Manifestations
Erythematous maculopapular
rash
Pruritic
Involves palms and soles and
spreads throughout the body
Blisters and ulcers - in severe
cases.
GIT - Manifestations
Diarrhoea ? secretory, voluminous (>2L/day)
Bleeding - life threatening intestinal
hemorrhage.
Nausea, vomiting.
Anorexia
Abdominal pain
Liver
Jaundice and hepatomegaly
Mainly cholestatic hepatitis
? lymphocytic infiltration of portal tracts
? damage to bile duct epithelium
? consequent destruction of bile ducts.
Increased liver enzymes
Increased serum billirubin
Diagnosis
TA-GVHD is probably underdiagnosed since it may be
wrongly attributed to
- Intercurrent infection
- Severe drug reaction
- Auto immune diseases
Histopathological/hematological features and
detection of donor lymphocytes or DNA (mixed
chimerism)
Diagnostic testing
Skin biopsy
superficial perivascular lymphocyte infiltrate
necrotic keratinocytes
bullae formation
Bone marrow examination
Hypocel ular/aplastic marrow
Only macrophages present
Liver biopsy
Smal bile duct degeneration & eosinophilic necrosis
Intense periportal inflammation
Lymphocytic infiltration
Definitive diagnosis-
Identification of donor derived lymphocytes in recipient
circulation/tissues+ presence of clinical symptoms
Differential diagnosis
Acute viral hepatitis
Severe drug reaction
Dengue fever and leptospirosis
Acute sero-conversion illness due to HIV
infection
Prognosis
Fatality
Profound marrow aplasia
Mortality>90%(1-3weeks)
Management of Suspected/proven
disease
Must be treated in a specialized unit
High dose steroids ?First line - antilymphocyte and
antiinflammatory activity
Methotrexate & Cyclosporine-A ? to prevent the disease
Steroid refractory GvHD
? Anti-thymocyte globulin (ATG)
? Azathioprine
? Intravenous immunoglobulins
Supportive therapy ? Antibiotics
Stem cell transplantation
Prevention
Prevention is better than cure
Gamma Irradiation of cellular Blood
component
- 25Gy- centre of blood bag
- 15Gy-peripheral part of blood bag
Photochemical treatment of platelets &
plasma
When to Irradiate
At a minimum, cellular components shall be irradiated
when:
1.A patient is identified as being at risk for TAGVHD
2.The donor of the component is a blood relative of the
recipient
3.The donor is selected for HLA compatability, by typing or
crossmatching.
AABB Technical Manual
Clinical Indications for Irradiated Components
Well-documented indications
? Intrauterine transfusions
? Premature, low-birthweight infants
? Newborns with erythroblastosis fetalis
? Congenital immunodeficiencies
? Hematologic malignancies or solid tumors (neuroblastoma,
sarcoma, Hodgkin disease)
? Components that are crossmatched, HLA matched, or
directed donations
? Fludarabine therapy
? Granulocyte components
Potential indications
? Other malignancies, including those treated with
cytotoxic agents
? Donor-recipient pairs from genetically homogenous
populations
Usual y not indicated
? Patients with human immunodeficiency virus
? Term infants
? Non-immunosuppressed patients
General aspects about Irradiation of Blood
components
Lymphocyte viability is retained in stored red cel s for at
least 3 weeks
TA-GvHD has been reported after transfusion of whole
blood, red cel s, platelets and granulocytes
TA-GvHD has not been described fol owing transfusion
- frozen deglycerolized red cells, which are thoroughly washed
free of leucocytes after thawing.
- cryoprecipitate
- fresh frozen plasma or
- fractionated plasma products
Shelf Life of Irradiated Products
Irradiated Red Blood Cel s
Red cells can be irradiated up to 14 d after collection
and stored for at least a further 14 d without
significant loss of viability
Shortened to 28 days after irradiation or until original
expiration date, whichever comes first
Where the patient is at particular risk from
hyperkalaemia, e.g. intrauterine or neonatal
exchange transfusion, it is recommended that red
cells be transfused within 24 h of irradiation or that
the cells are washed.
Platelets
No effect of Gamma irradiation below 50 Gy on
platelet function
Platelets can be irradiated at any stage during storage
and can thereafter be stored up to their normal shelf
life after collection.
Granulocytes
The evidence for irradiation damage to granulocyte
function is conflicting
But in any case granulocyte products should be
transfused as soon as possible after irradiation
All granulocytes should be irradiated before issue and
transfused with minimum delay.
Methods for Irradiation
Gamma Irradiators
X-ray Irradiators
(Gamma rays and X-rays are similar in their ability to
inactivate T lymphocytes in blood components at a given
absorbed dose)
Gamma Irradiators
Both cesium and cobalt irradiators are available
Expensive
Disposal present significant difficulties
These highly radioactive cores may present a security risk
in hospital settings
As the source decays, regular recalibration is required and
irradiation time progressively increases
Strict regulatory requirements are required
Cel Irradiator
X-ray Irradiators
Less Expensive
Absence of a radioactive source
Fewer regulatory requirements
Effective Dose of Radiation
Dose to the center of the irradiation field must be at
least 25 Gy
Minimum delivered dose delivered to any other portion
must be 15 Gy
No more than 50 Gy should be delivered to the product.
Special labels (radiochromic film labels which change
color upon being irradiated) are affixed to units to
confirm irradiation of an adequate dosage
Process takes 5minutes.
Cons of Irradiated Products
Reduced shelf life 35->28 days
Leakage of potassium
Theoretical risks
?Malignant change? Reactivation of latent virus?
Plastic leakage?
Practical issues
?Cost/upkeep/validation/security of irradiators
Non-irradiation Prevention Strategies?
Leukocyte reduction has been shown to
reduce the risk of TAGVHD, especially in a
genetically diverse population, but is not a
substitute for irradiation in at-risk populations.
Psoralen (S59) + ultra-violet A ? used for
pathogen inactivation
Conclusions
Prevention is only the key for this deadly disease.
Al donor blood and blood products for immuno
compromised, suspected or potential y immuno-
compromised patients should be irradiated.
As new potent immunosupressive drugs and biological
agents are introduced into practice, there is a need for
regular review of recommendations regarding irradiated
blood components.
References
1. Transfusion-Associated Graft-VersusHost Disease in Severe Combined
Immunodeficiency; S Sebnem Kilic, S Kavurt,S Balaban Adim: J Investig
Allergol Clin Immunol2010; Vol. 20(2): 153-156
2. Transfusion-associated graft-versus-host disease; D. M. Dwyre & P. V.
Holland :Vox Sanguinis, 2008 95;85?93
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
blood components prepared by the British Committee for Standards in
Haematology blood transfusion task force. British Journal of Haematology,
152: 35?51. doi:10.1111/j.1365-2141.2010.08444.x
4. Review - Transfusion-associated graft-versus-host disease, BJH
2002;117:275?287
References
5. Denise M. Harmening. Modern Blood Banking & Transfusion Practices. 6th
Edition.
6. http://www.bbguy.org/education/videos/whyirradiate/
7. Rossi's Principles of Transfusion Medicine
8. TA-GvHD management guidelines ?NHS
ThankYou
This post was last modified on 08 April 2022