Download MBBS Transfusion Medicine and Blood Bank Presentations 5 Irradiation Of Blood Components Lecture Notes

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