Irradiated and CMV negative Blood / Blood Components in Transfusion - Guideline for the Use of

Publication: 20/11/2012  --
Last review: 26/03/2019  
Next review: 01/03/2022  
Clinical Guideline
CURRENT 
ID: 3157 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2019  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for the Use of Irradiated and CMV negative Blood / Blood Components in Transfusion

Summary of Guideline/Protocol

TA-GvHD and CMV can cause potentially life threatening complications; therefore prevention is key to patient well-being. This guideline details the situations for which irradiated and/or CMV negative blood components must be used and for how long. It also details how to obtain patient informed consent in these special circumstances and how to request, prescribe irradiated and/or CMV negative blood components. This guideline also details how to perform the pre-administration bedside check of these special transfusion requirements so as to help ensure the correct blood component is selected and transfused to the correct patient, therefore preventing potentially serious health complications and/or death of patients. Also detailed is how to recognize signs/symptoms of TA-GvHD and/or CMV and to then diagnose these conditions.

Treatment / Management

1. Introduction

Transfusion Associated Graft versus Host Disease:
TA-GvHD (Transfusion Associated Graft versus Host Disease) is a very rare but usually fatal complication following transfusion of lymphocyte containing blood components (red cells, platelets and granulocytes)

The risk associated with an individual transfusion depends on the number and viability of contaminating T-lymphocytes, susceptibility of the recipient’s immune system to their engraftment and degree of immunological (HLA) disparity between donor and patient.

TA-GvHD has been reported in children with severe primary T lymphocyte immunodeficiencies characterized by an absence of T lymphocytes or a severe defect of T cell function.

In the newborn infant the presenting features of immunodeficiency syndromes may be unrelated to the immune defect (e.g. cardiac disease, hypocalcaemia, thrombocytopenia, eczema) and a high index of suspicion is required, particularly in infants less than 6 months old with recurrent or persistent respiratory or gastro-intestinal infections.

In older patients, a severe T lymphocyte deficiency can be induced by certain acquired conditions (e.g. Hodgkin’s disease) or certain immunosuppressive or cytotoxic treatments.

All severe T lymphocyte immunodeficiency syndromes should be considered as indications for irradiation of cellular blood components. Once a diagnosis of immunodeficiency has been suspected, irradiated components should be given while further diagnostic tests are being undertaken.

Transfusion transmission of CMV:
Transmission of CMV (cytomegalovirus) present in blood components can give rise to primary infection in CMV naïve recipients (transfusion-transmitted CMV) or to re-infection in previously infected individuals. CMV can be transmitted from blood donors with active (primary/reactivated) or latent infection; CMV may be present in circulating monocytes, or free in plasma as a result of primary infection or perhaps reactivation.

Cytomegalovirus is a herpes virus that gives rise to chronic, persistent and, for the most part, asymptomatic infection in a majority of adults. More severe disease may occur in certain groups, such as foetuses, neonates and severely immunosuppressed patients

The risk of transmission in multiply-transfused CMV negative recipients is greatly reduced by the provision of leucodepleted blood components and this is now viewed as sufficient to prevent CMV transmission in the majority of patients (Department of Health, 2012).

DH / SaBTO have reviewed the evidence around the replacement of CMV seronegative cellular blood components (both red cells and platelets) with leucodepleted blood components. The following conclusions were reached:

i. CMV seronegative red cell and platelet components should be provided for intra-uterine transfusions and for neonates (i.e. up to 28 days post expected date of delivery), and therefore all small sized blood packs and other cellular blood components intended for neonates should be provided as CMV seronegative. For ease, LTHT blood bank will provide CMV negative blood components up to 6 months of age).

ii. Granulocyte components should continue to be provided as CMV seronegative for CMV seronegative patients.

iii. CMV seronegative blood components should be provided where possible for pregnant women, regardless of their CMV serostatus, who require repeat elective transfusions during the course of pregnancy (not labour and delivery). This mainly applies to patients with haemoglobinopathies who are managed in specialist centres. However CMV seronegative blood components are not expected to be generally available in all hospitals and therefore for emergency transfusions in pregnant women, leucodepleted components are recommended.

iv. All blood components (other than granulocytes) in the UK now undergo leucodepletion, which provides a significant degree of CMV risk reduction. This measure is considered adequate risk reduction for all other patients requiring transfusion (haemopoetic stem cell transplant patients, organ transplant patients, and immune deficient patients, including those with HIV) without the requirement for CMV seronegative components in addition.

v. CMV PCR monitoring should be considered for all haemopoetic stem cell and solid organ transplant patients (even CMV negative donor/negative recipients) to allow early detection of any possible CMV infection (whether transfusion-transmitted or primary acquired infection).

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2.Available Components

Irradiated: Lymphocyte viability is retained in stored red cells for at least 3 weeks and TA-GvHD has been reported after transfusion of whole blood, red cells, platelets and granulocytes.

TA-GvHD has not been described following transfusion of cryoprecipitate, fresh frozen plasma or fractionated plasma products, such as clotting factor concentrates, albumin and intravenous immunoglobulin. Therefore only red cells, platelets and granulocytes require irradiating.

 

CMV negative: The status of CMV negative applies to red cells and platelets only.

2.1 Shelf Life
Irradiating red cells shortens the expiry to 14 days. When checking blood components before administering them, particular attention should be paid to checking the expiry date.

CMV negative blood components shelf life is not affected by the CMV negative status.

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3. Indications for Use


NB: *Irradiated ‘blood component’ refers to both red cells and platelets
**CMV negative blood components includes red cells and platelets


Patient Group / Condition/Treatment

Special blood requirement

Further information / Length of time to receive special blood requirements

Haematology Patients:

 

 

Aplastic Anaemia
- patients likely to receive allogeneic HSCT and/or treated with immunosuppressive therapy (ATG, ALG, alemtuzumab)

Irradiated

Irradiated red cells & platelets  for life *

 

Hodgkin’s Disease (Hodgkin’s Lymphoma)

Irradiated

Irradiated red cells & platelets  for life *

Patients who have unclassified T cell immunodeficiency

Irradiated

Irradiated red cells & platelets  for life *

Patients who have received Purine Analogue Drugs

  • Fludaribine
  • Cladribine
  • Deoxycoformicin
  • Chlorodeoxyadenosin
  • Nelarabine

Irradiated

Irradiated red cells & platelets  for life *

Patients who have received Purine Antagonist Drugs

  • Bendamustine
  • Clofarabine

Irradiated

Irradiated red cells & platelets  for life *

Patient undergoing BM or PBSC harvest

Irradiated

Irradiated red cells & platelets from 14 days prior to & during stem cell harvesting.

Irradiated red cells & platelets from 14 days prior to pre-conditioning chemo for all allograft BMT/PBSCT

Patients proceeding to autograft will  remain on irradiated red cells & platelets for life *

Post Allogeneic  HSCT

Irradiated

Irradiated red cells & platelets  for life *

 

Post Auto HSCT

Irradiated

Irradiated red cells & platelets  for life *

Patients receiving HLA matched components

Irradiated

Only the HLA matched components need to be irradiated

Patient who have received immunosuppressive antibody treatments

  • anti-thymocyte globulin (ATG)
  • anti-lymphocyte globulin (ALG)
  • alemtuzumab / Campath (anti-CD52)
  • Muromonab (OKT3)

Irradiated

Irradiated red cells & platelets for life*

 

Patients receiving granulocytes

Irradiated
CMV Neg (for all CMV Neg patients)

Once irradiated, transfuse with minimum delay
In patients receiving granulocytes only, it is only the granulocytes that need to be irradiated/CMV Neg

Bone marrow/stem cell donors

Irradiated

Irradiated red cells/platelets for 14 days prior to and/or during bone marrow/stem cell harvest

Solid Organ Transplant Patients:

 

 

Renal/Liver Patients:

 

 

Patient who have received immunosuppressive antibody treatments

  • alemtuzumab (anti-CD52)/Campath
  • Muromonab (OKT3)
  • ATG

Irradiated

Irradiated red cells & platelets  for life *

 

Live renal organ donors

Irradiated

Irradiated red cells & platelets  for 7 days prior to and during organ transplantation

Obstetric Patients:

 

 

Intra-Uterine Transfusion (IUT)

Irradiated
CMV Neg
Group O Neg

Irradiated platelets transfused in-utero to treat allo-immune thrombocytopenia

Red cells transfused in-utero will be less than 5 days old & irradiated with a Hct no greater than 0.75

Transfuse irradiated blood components (red cells & platelets) within 24 hours of irradiation

Baby must receive irradiated blood components (red cells & platelets) until 1 year old*

Baby must receive CMV negative blood components (red cells & platelets) until 6 months old **

 

Pregnancy

             CMV Neg

All women receiving elective antenatal transfusion should receive:

CMV negative blood components** - not necessary during labour or post natal.

Neonates: All children to receive CMV negative blood components until 6 months of age*

Exchange Transfusion (Neonatal)

Irradiated
CMV Neg
Group O Neg

Red cells will be less than 5 days old & Group O Neg

Transfuse irradiated blood red cells & platelets  within 24 hours of irradiation

Must have irradiated if previous IUT; otherwise irradiated if time allows

Baby must receive CMV negative blood components (red cells & platelets) until 6 months old**

 

Post Intra-Uterine Transfusion

Irradiated
CMV Neg

Babies post IUT must receive irradiated blood components until 1 year old

Baby must receive CMV negative blood components (red cells & platelets) until 6 months old **

 

Paediatrics: All children to receive CMV negative blood components until 6 months of age

Di George syndrome (3rd and 4th arch/pouch syndrome)

Irradiated

Irradiated red cells & platelets  for life *

SCID – Severe Combined Immunodeficiency

Irradiated

Irradiated red cells & platelets  for life *

Wiskott Aldrich Syndrome

Irradiated

Irradiated red cells & platelets  for life *

Purine nucleoside phosphorylase deficiency (PNP)

Irradiated

Irradiated red cells & platelets  for life *

Leiner’s disease (Leiner-Moussous disease, Erythrodermia desquamativa Leiner)

Irradiated

Irradiated red cells & platelets  for life *

Reticular dysgenesis (aleukocytosis)

Irradiated

Irradiated red cells & platelets  for life *

Adenosine deaminase deficiency

Irradiated

Irradiated red cells & platelets  for life *

MHC class I or class II deficiency (Bare Lymphocyte Syndrome)

Irradiated

Irradiated red cells & platelets  for life *

Leucocyte adhesion deficiency

Irradiated

Irradiated red cells & platelets  for life *

Omenn’s syndrome

Irradiated

Irradiated red cells & platelets  for life *

Ataxia telangiectasia (Louis–Bar syndrome, Boder-Sedgwick syndrome)

Irradiated

Irradiated red cells & platelets  for life *

Cell-Mediated Immunodeficiency

Irradiated

Irradiated red cells & platelets  for life *

General:

 

 

Patient who have received immunosuppressive antibody treatments

  • anti-thymocyte globulin (ATG)
  • anti-lymphocyte globulin (ALG)
  • alemtuzumab (anti-CD52)
  • Muromonab (OKT3)

Irradiated

Irradiated red cells & platelets  for life *

Patients receiving components from a first or second degree relative

Irradiated

Only the components from the relative need to be irradiated

Patients receiving umbilical cord blood transplant under trial conditions

Irradiated
CMV Neg

Irradiated red cells & platelets  for life *

CMV negative blood components** for the duration of the cord blood transplant trial and then follow local policy

 

 

Key: * for ease and to prevent confusion, this time limit recommendation (which does not follow national recommendations) has been lengthened for LTHT policy to ensure patient safety
NB:  there is no need to routinely irradiate blood components for patients with HIV
NB:  there is no need to provide CMV negative blood components for patients with HIV and/or organ transplant patients

See appendices 1 & 3 for printable lists of the above conditions/requirements to display in clinical areas.

3.1 Informing Blood Bank of which Patients Require Irradiated and/or CMV Negative Blood Components:

All special requirements detailed in section 3 above, should be clearly indicated on the Transfusion Request Form and followed up with a confirmatory telephone call to Blood Bank.

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4. Signs & Symptoms of TA-GvHD / CMV

The early features of TA-GvHD are fever, maculopapular skin rash, diarrhoea and hepatitis occurring 1–2 weeks after transfusion. Bone marrow involvement produces severe hypoplasia with profound pancytopenia.

Signs & symptoms of CMV: This herpes virus causes few symptoms in the healthy but can pose a severe infection risk in foetuses and neonates and in the immunosuppressed, it can affect any part of the body but most commonly eyes, lungs and GI tract. It may present as flu like symptoms.

4.1 Diagnosing TA-GvHD / HEV / CMV

Diagnosis of TA-GvHD is usually made by biopsy of skin, gut or liver supported by evidence of persistence of donor lymphocytes. The presence of cells of donor origin may be demonstrated by polymerase chain reaction in peripheral blood or short tandem repeat analysis using peripheral blood and skin biopsies from affected and non-affected sites in the patient, and peripheral blood samples from the implicated donors.

Diagnosis of HEV is usually via blood sample (red top tube with yellow inner) sent to virology. LFTs may be normal or demonstrate a mild hepatitis picture - however, this may be assigned to other causes e.g. drug induced. IgG or IgM anti-HEV may be negative. Confirmation is with HEV PCR. Hepatic histology may demonstrate non-specific hepatitis; confirmation is with HEV Ag immunohistochemistry.

Diagnosis of CMV is usually made via a blood sample (lavender top EDTA tube) sent to virology. CMV infection is of particular significance to immunocompromised patients. The virus affects various organs and causes pneumonia, retinitis, hepatitis, colitis, and meningoencephalitis amongst others. It also causes congenital infections and 10% of congenitally infected babies will have severe, classic "cytomegalic inclusion disease" with intrauterine growth retardation, jaundice, hepatosplenomegaly, pneumonia and CNS damage.

4.2 Reporting Suspected Cases of TA-GvHD and/or CMV

Any evidence of suspected TA-GvHD and/or CMV must immediately be reported to Blood Bank and the Hospital Transfusion Team for investigation.

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5. Effects of Irradiation on Blood Components:

Irradiated components not used for the intended recipient can safely be returned to stock to be used for recipients who do not require irradiated components. The reduction in shelf life must be observed.

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6. Patient Information

There is no special information leaflet available for patients requiring CMV negative blood components.

Patients needing irradiated blood components should be offered an information leaflet detailing why they need irradiated blood components. Patients should also be presented with an ‘alert’ card (found within the patient information leaflet) for them to carry at all times. It should be explained to the patient to show this card to ward staff whenever they present for a transfusion either at their treating hospital or any other hospital they attend.

The ‘alert’ card should be given to patients by the admitting or prescribing nurse or doctor.

Within the irradiated blood components information leaflet there are also ‘alert’ stickers for admitting staff to place on the front of patient case notes. This will alert all Trust staff to the fact that the patient needs to receive irradiated blood components.

The leaflet; “Information for patients needing irradiated blood” is available within clinical areas or, from the Hospital Transfusion Team ext: 23868 / 23984 / 28337.

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7. How to Request & Prescribe Irradiated and CMV Negative Blood Components

To ensure a patient receives irradiated / CMV negative blood components it is essential to fully and correctly complete thetransfusion request card detailing the patient’s diagnosis and reason for request. 

NB: The doctor caring for the patient must also telephone the issuing Blood Bank to inform them of the need for irradiated and/or CMV negative blood components.

It can take up to 30 minutes to irradiate blood components at the National Blood Service centre, and a further delay for these to arrive in Blood Bank.

The need for irradiated / CMV negative blood components must be indicated on the patient’s transfusion authorisation (prescription) chart. 

Because of their short shelf-life, platelets are not routinely stored in blood bank but ordered from the National Health Service Blood & Transplant (NHSBT) as required. Request for platelets should be made at the earliest possible opportunity by telephoning the hospital Blood Transfusion Laboratory (Ext: 23398 (LGI) & ext: 65559 (SJUH)), followed by the relevant blood sample if the patient’s blood group is unknown to the Lab. Once the request is received, the Transfusion Laboratory will order platelets to be delivered from the National Blood Service Centre.  N.B. Requests will take at least 2 hours before delivery to the clinical area depending on availability, type of request (e.g. irradiated) and level of traffic between NBS and the LTHT hospital.

In emergency situations such as major haemorrhage, staff must communicate early with the Blood Bank.

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8. Pre-administration bedside check

All irradiated, and/or CMV negative components should be labelled as such. Check compliance with the need for irradiated, CMV negative components between transfusion prescription chart and the NBS label attached to the blood component.

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9. Reporting Incidents of Non Compliance with Special Transfusion

Requirements

Since its inception in 1996, the UK Serious Hazards of Blood Transfusion (SHOT) scheme has recorded 14 fatal cases of TA-GvHD. Only three cases have been reported since the introduction of universal leucodepletion in the UK.
           
LTHT policy states that all incidents where non-irradiated components are transfused to high-risk patients must be reported to the Blood Transfusion Laboratory / Hospital Transfusion Team immediately.

Incidents where non-CMV negative blood component transfusions have been administered must be reported to the Hospital Transfusion Team and the Blood Transfusion Laboratory must be informed.

All of the above incidents are SHOT (Serious Hazards of Transfusion, UK haemovigilence scheme) reportable.

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10. Written Informed Consent for Transfusion of Irradiated Blood Components

ALL patients are required to give their written informed consent before transfusion of any blood or blood component.

For further information see the LTHT policy on obtaining written informed consent for blood / blood components: detail.aspx?ID=1217

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Provenance

Record: 3157
Objective:

Aims

To improve the management of patients who require irradiated and/or CMV negative blood/blood components

Objectives
To provide evidence-based recommendations for the appropriate and safe use of irradiated and / CMV negative blood / blood components. To guide clinicians on the correct procedures for patient selection, requesting and prescribing irradiated and CMV negative blood / blood components

Clinical condition:

Any clinical conditions where there is a risk of developing Transfusion Associated Graft versus Host Disease (TA-GvHD) or CMV (cytomegalovirus) transmission

Target patient group: Haematology, Renal, Obstetrics, Neonates, Paediatrics and any clinical conditions where there is a risk of developing Transfusion Associated Graft versus Host Disease (TA-GvHD) or CMV transmission.
Target professional group(s): Secondary Care Doctors
Adapted from:

Evidence base

Addendum to the Guidelines on the use of irradiated blood components. British Society for Haematology Task Force (2012); 6.11.12

British Society for Haematology (2010).  Use of irradiated blood components. https://b-s-h.org.uk/guidelines/guidelines/use-of-irradiated-blood-components/

British Society for Haematology (2004).  Guidelines on transfusion for fetuses, neonates and older children  British Society for Haematology 2016

Cytomegalovirus Tested Blood Components Position Statement. SABTO Advisory Committee On Safety Of Blood, Tissues And Organs (2012)

Handbook of Transfusion Medicine. Fifth Edition. (2013) editor: Dr D N Norfolk.

LTHT Guideline on Use of Blood Components on the Neonatal Unit: detail.aspx?ID=542

LTHT Policy on Obtaining Written Informed Consent for Blood / Blood Components.: detail.aspx?ID=1217

LTHT Policy for Safer Transfusion Procedures: detail.aspx?ID=1864

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

Appendix 1

Clinical Indication for Irradiated Blood Components.   
IT IS THE PRESCRIBER’S RESPONSIBILITY TO CHECK WITH THE TRANSFUSION LABORATORY, THE STATUS OF ALL AT RISK PATIENTS REGARDING THEIR NEED FOR SPECIAL TRANSFUSION REQUIREMENTS

  • ALL transfusions to patients where the component is from a first or second degree relative.
  • ALL patients receiving HLA (Human Leucocyte Antigen) matched/selected blood and components. Only the HLA matched/selected components need irradiating
  • ALL patients receiving red cells for intra-uterine transfusion (IUT).
  • ALL neonates receiving an exchange transfusion (where time allows).
  • ALL platelets to be transfused in-utero to treat foetal allo-immune thrombocytopenia.
  • ALL red cells and platelets for neonates who have had a previous intra-uterine transfusion (red cells or platelets). Should receive irradiated blood components until 1 year old
  • ALL babies suffering from immunological deficiencies listed in table 1, or those suffering from an unassigned immunodeficiency.
  • Bone marrow donors from 14 days prior to or during a bone marrow harvest
  • Patients undergoing either bone marrow harvest or peripheral stem cell harvest during and for 14 days BEFORE the harvest. To continue on irradiated blood components until after PBSCT
  • Patients undergoing allo bone marrow transplant and/or peripheral blood stem cell transplant, during and post transplant. This should be continued for life.
  • Patients undergoing autologous bone marrow transplant and/or peripheral blood stem cell transplant. This should be continued for life.
  • ALL patients with Hodgkin's Disease. This should be continued for life.
  • ALL patients who are undergoing treatment with any purine analogue / purine antagonist: these drugs have long lasting effects and should receive irradiated blood components for life:
    1. Fludarabine
    2. Cladribine
    3. Deoxycoformycin (DCF) (otherwise called Pentostatin)
    4. Chlorodeoxyadenosin (CDA)
    5. Bendamustine
    6. Clofarabine 
    7. Nelarbine 

All patients undergoing treatment with:

  • CamPath (alemtuzumab)
  • Muromonab (OKT3)
  • Antithymocyte globulin Horse (ATGAM) / Anti-human Thymocyte Immune Globulin (rabbit): both also referred to as ‘ATG’
  • Antilymphocyte globulin (ALG)

The above drugs have long lasting effects and should receive irradiated blood components for life.

Table 1 - Immunodeficiencies requiring irradiated blood and components.

SCID - Severe Combined Immunodeficiency
Di George's syndrome - 3rd and 4th arch/pouch syndrome
Wiskott Aldrich Syndrome
Purine nucleoside phosphorylase deficiency
Lenier's disease
Cell-Mediated immunodeficiency (not classified)
Reticular dysgenesis
Adenosine deaminase deficiency
MHC class I or class II deficiency
Leucocyte adhesion deficiency
Omenn's syndrome
Ataxia telangiectasia

 

Table 2 - Immunodeficiencies NOT requiring irradiated blood and components.

CMC - Chronic mucocutaneous candidiasis
HIV/AIDS

Appendix 1: List correct at time of publication: March 2019

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Appendix 3 - Clinical Indication for CMV Negative Blood Components

Clinical Indication for CMV Negative Blood Components

CMV negative blood components are only recommended for use in:

  • CMV seronegative red cell and platelet components should be provided for elective transfusions during pregnancy (not during delivery).
  • CMV seronegative red cell and platelet components should be provided for intra-uterine transfusions and for neonates (i.e. for ease, blood bank will supply CMV negative blood components for up to 6 months post delivery)
  • Granulocyte components should continue to be provided as CMV seronegative for CMV seronegative patients. Granulocyte components cannot be leucodepleted

CMV PCR monitoring should be considered for all haemopoeitic stem cell and solid organ transplant patients (even CMV negative donor/negative recipients) to allow early detection of any possible CMV infection (whether transfusion-transmitted or primary acquired infection).

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Glossary of terms

Blood component – in this guideline refers to: platelets & red cells
BMT – Bone Marrow Transplant

CMV – Cytomegalovirus.

DIC- Disseminated Intravascular Coagulation

FFP- Fresh Frozen plasma

GvHD – Graft versus Host Disease (as seen in bone marrow/stem cell transplant patients)

HLA- Human Leucocyte Antigen

HSCT - Haematopoietic Stem Cell Transplant (refers to stem cells originating from  either both bone marrow or peripheral blood)

IUT – Intra-Uterine Transfusion

Irradiated - Use of X or gamma irradiation to treat cellular products i.e. red cells and/or platelets

MB FFP - Methylene Blue Fresh Frozen Plasma

NBS - National Blood Service (AKA: NHSBT)

NHSBT – National Health Service Blood & Transplant (AKA: National Blood Service)

PBSCT – Peripheral Stem Cell Transplant

SABTO – Safety of Blood, Tissues and Organs (Department of Health sub committee)

TA-GvHD – Transfusion Associated Graft versus Host Disease

TBI – Total Body Irradiation; used for autologous PBSCT

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The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.