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

• Summary of Guideline
• Aims
• Treatment/Management
• Appendix 1 Clinical Indication for Irradiated Blood Components
• Appendix 2 Clinical Indication for CMV Negative Blood Components
• Appendix 3 List correct at time of publication: December 2020

Summary of Guideline

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.

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Aims

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

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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 multiple 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:

1. 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).
2. Granulocyte components should continue to be provided as CMV seronegative for CMV seronegative patients.
3. 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.
4. 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.
5. 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).

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.

3.   Indications for Use
NB: *Irradiated ‘blood component’ refers to both red cells and platelets
**CMV negative blood components includes red cells and platelets

See appendices 1, 2 & 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.

* 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 / 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 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.

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.

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.

Patient Information Leaflet	‘Alert’ card / sticker

https://hospital.blood.co.uk/patient-services/patient-blood-management/patient-information-leaflets/

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 the transfusion 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.

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.

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.

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 wherever clinically possible.

For further information see the LTHT policy on obtaining written informed consent for blood / blood components: http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=1217

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Appendix 1 Clinical Indication for Irradiated Blood Components

Appendix 1: List correct at time of publication: January 2021

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 

Haematology patients undergoing treatment with the drugs below should receive irradiated blood components for life.:

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

NB: 2020 Guideline on the use of Irradiated Blood Components recommends that Irradiated components are not required for Solid Organ Transplant patients receiving Alemtuzumab or ATG/CD52 immunosuppressant.

Table 1 - Immunodeficiencies requiring irradiated blood and components.

Table 2 - Immunodeficiencies NOT requiring irradiated blood and components.

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Appendix 2 - 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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Appendix 3: List correct at time of publication: December 2020

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 (or: 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 subcommittee)

TA-GvHD – Transfusion Associated Graft versus Host Disease

TBI – Total Body Irradiation; used for autologous PBSCT