This guideline is for all staff involved in prescribing, supplying and administering blood and blood components throughout NHS Ayrshire and Arran. It should be used in conjunction with the NHS Ayrshire and Arran Blood Transfusion Policy. (The aim of the Blood Transfusion policy is to ensure that the right blood is given to the right patient at the right time, every time.)

This guideline focuses on patients who have special transfusion requirements and aims to:

1. Provide healthcare professionals with clear guidance on when:

• • Cytomegalovirus (CMV) seronegative components are indicated.
  • Irradiated components and/or other special requirements for transfusion are indicated and where responsibilities lie.

2. Outline the process of notification to the Blood Transfusion Lab, of patients with special requirements.
3. Outline how this information will be disseminated across NHS Ayrshire and Arran.
4. Outline how errors should be reported if they arise.

Advice on blood transfusion may be obtained from Biomedical Scientist (BMS) staff in Blood Transfusion, from Haematology Medical Staff and from the Transfusion Practitioner.

This guideline was prepared for NHS Ayrshire and Arran Hospitals Transfusion Committee (HTC) by the Hospital Transfusion Team (HTT) and reflects current standards. It will be reviewed by the HTC every two years to accommodate future changes in the provision of healthcare in NHS Ayrshire and Arran and in the provision of Blood and Blood Components.

Special transfusion requirements cover a range of additional specifications or processing of standard blood components. The most commonly requested special requirements in practice are cytomegalovirus (CMV) seronegative components and irradiated components.

CMV belongs to the herpes family and in the healthy population causes a self limiting illness. It is cell associated and therefore can be transmitted in cellular blood components (red cells, platelets and granulocytes). Typically it causes a subclinical illness similar to infectious mononucleosis (glandular fever). In immunocompromised patients it can result in potentially fatal pneumonitis or disseminated CMV infection. For this reason CMV seronegative products should be used for the selected group of patients, listed below.

The requirement for CMV seronegative blood components was recently reviewed by the Advisory Committee on the Safety of Blood, Tissue and Organs (SaBTO)¹. Universal leucodepletion, introduced by UK blood services in 1999, primarily as a variant Creutzfeldt-Jakob disease (vCJD) risk reduction measure, results in a three log depletion of white cells. This is generally accepted to render components “CMV safe”. As CMV is a common virus and the prevalence of anti-CMV in the UK adult population is 50-60%, it not possible to provide CMV seronegative products for all recipients. Components that have been leucocyte depleted to less than 5 x 10⁶/unit have a significant reduction in the risk of CMV transmission.

Monitoring selected patient groups for CMV infection with pre-emptive therapy where required, has been shown to be a successful strategy in certain groups (solid organ transplants, haematopoietic stem cell transplants).

CMV seronegative components should continue to be used where leucodepletion is not possible (granulocyte transfusions) or where the potential severity of the consequences of CMV infection, and/or the difficulty in monitoring for infection are considered too great (intrauterine transfusion (IUT), transfusions in neonates up to 28 days post expected date of delivery (EDD), elective transfusions in pregnancy).

In summary, CMV Negative components should be used for:

• all granulocyte transfusions
• elective transfusions in pregnancy (not during labour or delivery)
• intrauterine transfusion (IUT)
• neonates (up to 28 days post EDD)

Irradiation is the only known method of preventing transfusion associated graft versus host disease (TaGvHD). This is a rare but fatal complication of blood transfusion. It results from engraftment and clonal expansion of human leukocyte antigen (HLA) compatible donor lymphocytes. Clinically TaGvHD presents with fever, rash, diarrhoea, hepatitis and pancytopenia, 4-30 days after transfusion. This complication of transfusion is eliminated by inactivation of donor lymphocytes by irradiation. The risk associated with individual transfusions depends on the number and viability of contaminating lymphocytes, susceptibility of the host’s immune system to their engraftment and the degree of immunological disparity between donor and recipient^2,3.

As new treatments are developed there may be additional therapeutic agents for which irradiated components are required. If there is any concern about the need for irradiated components, prescribers should first check with a pharmacist or consultant haematologist. As a guide, irradiated blood is required in the following situations:

• All patients treated with purine analogue drugs (fludarabine, clofarabine, cladribine, bendamustine and deoxycoformycin/pentostatin) should receive irradiated blood components indefinitely.
• Patients with chronic lymphocytic leukaemia (CLL) or other haematological diagnosis treated with alemtuzumab should receive irradiated components.
• Patients with aplastic anaemia undergoing treatment with ATG or alemtuzumab should receive irradiated blood components.
• Patients receiving ATG or other T-lymphocyte-depleting serotherapy for rare types of immune dysfunction conditions should receive irradiated blood components.
• Where a patient is to donate bone marrow/peripheral blood stem cells, either for autologous stem transplant or to be given to an allogeneic transplant recipient, during and for 7 days before stem cell collection.
• Where the recipient is undergoing/has undergone an autologous bone marrow/peripheral blood stem cell transplant, from initiation of conditioning chemotherapy/radiotherapy until 3 months post transplant (6 months if conditioned with total body irradiation).
• Where the recipient is receiving an allogeneic bone marrow/peripheral blood stem cell transplant, from initiation of conditioning chemotherapy/radiotherapy, continued until all the following criteria are met:
  • >6 months have elapsed since the transplant date
  • the lymphocyte count is >1.0 x 10⁹/l
  • the patient is free of active chronic GvHD
  • the patient is off all immunosuppression.
• Where the patient has been given a diagnosis of Hodgkin Lymphoma, from diagnosis and continued for life.
• Where HLA-selected blood products are to be transfused.
• Any directed donation (transfusion of blood/platelets from a first or second degree relative).
• All blood/platelets for intrauterine transfusion (IUT), or for neonates who have previously received an intrauterine transfusion, for 6 months post EDD.
• Blood for neonatal exchange transfusion
• All granulocyte transfusions.
• Patients undergoing peripheral blood lymphocyte collections for future CAR-T cell re-infusion should receive irradiated cellular blood components for 7 days prior to and during the harvest. Irradiated blood components should continue to be used until 3 months following CAR-T cell infusion unless conditioning, disease or previous treatment determine indefinite duration, e.g. previous diagnosis of HL or previous purine analogue treatment.
• Where the patient has a congenital disorder of cell mediated immunity e.g. DiGeorge syndrome, Severe combined immunodeficiency (SCID). For advice on which disorders pose a risk, see BSH Guidelines clinical use of irradiated blood components .

Daratumumab and isatuximab are monoclonal antibodies that can be used in the treatment of myeloma. The antibodies are directed against the CD38 surface antigen that is present on plasma cells. Daratumumab and isatuximab interfere with the indirect antiglobulin test (IAT). ABO and D typing are not affected. The plasma from patients who have been treated with these anti CD38 antibodies will usually react weakly positive in the antibody screen and be pan-reactive in antibody identification panels; thus the presence of daratumumab/isatuximab has the potential to mask an underlying alloantibody. Donor red cells will be incompatible in the crossmatch. 

Before treatment with daratumumab or isatuximab is initiated, Blood Transfusion must be informed. This should include the date a patient is to commence treatment. It is essential that 2 x 7.5ml EDTA blood transfusion samples are sent for group and screen and extended phenotyping or genotyping prior to the first treatment dose.  

The treatment is given at regular intervals for as long as there is a clinical response.  On cessation of therapy, the antibody can persist in the patient’s circulation for up to six months therefore Blood Transfusion must also be informed once treatment is stopped.

Primary IgA deficiency, defined as selective IgA < 0.06g/l in adults, with normal levels of IgG and IgM, not secondary to other causes is relatively common (1:700 Caucasians). 20-40% of these individuals have anti-IgA-antibodies although these are a poor predictor of possible transfusion reactions. Patients with IgA deficiency may have allergic or anaphylactic reactions to blood components, however severe transfusion reactions in this group of patients are extremely rare (1:20,000 – 1:47,000 transfusions). Most IgA deficient patients with or without anti-IgA-antibodies will not experience severe reactions with standard components. Plasma reduced or IgA deficient components can be supplied, however this may lead to a delay in transfusion and the consequences of the delay should be balanced against the risk of a reaction.

Patients with IgA deficiency receiving a transfusion should be closely monitored in a clinical area where severe allergic and anaphylactic reactions can be managed.

In cases where there is a history of severe allergic/anaphylactic transfusion reactions, the use of components from an IgA deficient donor should be considered if it will not cause significant delays. Transfusion requirements for patients with IgA deficiency should be discussed with the local haematologist.

Plasma-reduction (previously known as washing) of cellular components (red cells and platelets) reduces levels of potentially harmful substances, e.g. serum proteins (IgA), antibodies, additive solutions, electrolytes (K+) etc. The process results in some cell losses, and takes several hours to complete. Plasma reduced components have a reduced shelf life. The indications for plasma reduced components include:

• Recurrent and/or severe allergic reactions or febrile reactions to transfusion which are not abolished by the use of leucodepleted components.
• IgA deficient patients if history of allergic/anaphylactic reactions.
• Patients with unexplained hypotensive transfusion reactions.

The Scottish National Blood Transfusion Service (SNBTS) has identified that the donor base in Scotland is changing and that it is more likely than previously, that donors with sickle cell trait may donate blood. Testing of blood donations for HbS is therefore being introduced to ensure HbS negative blood can be provided to patients who need it.

Red cell components which have been tested for the presence of HbS will be labelled as ‘HbS negative’ or ‘HbS positive’. Red cell components which have not been tested will not be labelled with either modifier. This is similar to the way which components tested for CMV are managed and labelled.

The Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee (JPAC) advise that HbS negative red cells should be selected:

• for intrauterine transfusion
• for transfusion to neonates
• for transfusion to people with sickle cell disorders.

Once a patient has been identified as having a requirement for special blood components, the Special Requirements of Blood Transfusion Laboratory Request Form, used throughout NHS Ayrshire and Arran should be printed.

The fully completed form should be sent to Blood Transfusion at Crosshouse Hospital. The information held on this form will be shared with Blood Transfusion Labs throughout NHS Ayrshire and Arran.

The clinician responsible for the patient should ensure that the patient’s special requirements for transfusion are documented in their case records. The form should be signed by the consultant in charge of the patient’s care. It should be photocopied and a copy filed in the case records with the second copy forwarded to Blood Transfusion. If the patient has been identified as having special blood component requirements out with core working hours and a consultant is not available, please telephone Blood Transfusion as an interim measure and progress paperwork as described at earliest opportunity.

Complete information will not be disseminated throughout the local Blood Transfusion Labs until a consultant signed copy of the special requirements form is received by Crosshouse Blood Transfusion.

If the need for special blood components changes, an updated form should be forwarded to the hospital Blood Transfusion Lab so records can be amended.

As patients transfer between hospital sites, it is important that their transfusion requirement information is available throughout the hospital Blood Transfusion Labs. Once a consultant signed form is received at Crosshouse Blood Transfusion, the information on the form will be uploaded into the Blood Transfusion Laboratory Information System (LIMS) and the requesting consultant notified, to ensure they are aware the laboratory tasks have been completed.

Please note should Blood Transfusion Labs out with NHS Ayrshire and Arran require patient special requirement information then it is the responsibility of the requesting consultant to ensure a copy of Special Requirements of Blood Transfusion Laboratory Request Form is sent to the appropriate health board Blood Transfusion Lab.

Currently it is not a legal requirement in the United Kingdom for written consent to be obtained before transfusion of blood components. It is considered a standard of good transfusion practice to ensure that the patient/parent/carer receives adequate information regarding the transfusion. This discussion should include information about the risks and benefits of transfusion as well as information relating to available alternatives, for example, iron supplementation and must be documented in the case records. Nursing and medical staff therefore, have a professional duty to ensure that they have adequate knowledge of transfusion related issues or that they can access the information and support required by patients undergoing a transfusion.

Booklets are available specifically for patients who require irradiated components and all patients receiving irradiated components should be given these before their first transfusion. They should also be counselled and told to inform nursing and medical staff of this requirement before any future transfusions. Patients should be given a card to carry documenting their special transfusion requirement. An adhesive sticker, taken from the information leaflet, should be placed on the front of case records where these exist, detailing the requirement. It is the responsibility of the prescribing practitioner to ensure these steps are undertaken.

Information for patients requiring irradiated blood 

Information for patients with red cell antibodies 

Receiving a blood transfusion 

There have been 13 reported cases of TaGVHD since 1996 but no cases in the last 12 years. 2 cases were reported in leucodepleted components (1998-99 and 2000-01) indicating that while leucodepletion significantly reduces, it does not eradicate the risk of this condition. It is important therefore that appropriate products are provided for patients at risk.

Errors do occur and the Serious Hazards of Transfusion (SHOT) 4 report 2021 shows 266 cases where special requirements were not met, a decrease from 323 in 2020.

It is important that any errors are documented appropriately to ensure that steps can be taken to avoid them in the future. If it becomes apparent that a patient has failed to receive appropriate components, Blood Transfusion must be informed immediately. The incident will be fully investigated and reported on Datix by the Clinical teams and to SHOT by the Hospital Transfusion Team.

Special requirements of blood transfusion laboratory request form

1. Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO). Cytomegalovirus tested blood components position statement.  Available from: http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_133086.pdf
2. Hoffbrand AV, Catovsky D, Tuddenham EDD, Green AR. Postgraduate haematology. Sixth edition. Chichester: Wiley-blackwell, 2011. Chapter 16. Clinical Blood Transfusion. p268-300.
3. Foukaneli T et al. Guidelines on the use of irradiated blood components. BJ haem. 2020; 191(5): p704-724. Available from: https://doi.org/10.1111/bjh.17015.
4. Serious Hazards of Transfusion Available from: http://www.shotuk.org/
5. New HV et al. Guidelines on transfusion for fetuses, neonates and older children. BJ haem. 2016; 175(5): p.784-828. Available from: https://doi.org/10.1111/bjh.14233
6. Murphy MF, Pamphilon DH. Practical Transfusion Medicine. Third Edition. Chichester: Wiley-Blackwell, 2009. Chapter 13. Transfusion Transmitted Infection. p.122-145. 
7. Public Health England. Hepatitis E: symptoms, transmission, treatment and prevention. Updated 14 May 2020. Available from:https://www.gov.uk/government/publications/hepatitis-e-symptoms-transmission-prevention-treatment/hepatitis-e-symptoms-transmission-treatment-and-prevention
8. WHO. Hepatitis E. Available from: http://www.who.int/mediacentre/factsheets/fs280/en/
9. Oteng-Ntim E et al. Management of sickle cell disease in pregnancy. A British Society for Haematology Guideline. 2021. BJ haem. 194(6); p.980-995. Available from:https://doi.org/10.1111/bjh.17671
10. Walewska R et al. Guideline for the treatment of chronic lymphocytic leukaemia. 2022. BJ haem. 197(5); p.544-557. Available from: https://onlinelibrary.wiley.com/doi/10.1111/bjh.18075
11. Follows GA et al. Guideline for the first-line management of Classical Hodgkin Lymphoma — A British Society for Haematology guideline. 2022. BJ haem. 197(5); p558-572. Available from: https://onlinelibrary.wiley.com/doi/10.1111/bjh.18083
12. Trompeter S et al. Position paper on International Collaboration for Transfusion Medicine (ICTM) Guideline ‘Red blood cell specifications for patients with hemoglobinopathies: a systematic review and guideline’. 2020. BJ haem. 189(3); p.424-427. Available from: https://onlinelibrary.wiley.com/doi/10.1111/bjh.16405
13. Department of Health and Social Care. Blood transfusion: patient consent. 2020. Available from: https://www.gov.uk/government/publications/blood-transfusion-patient-consent

ATG: Anti-thymocyte globulin treatment, used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anaemia.

BSH: British Society for Haematology - teams of expert consultants and clinical scientists currently practising in the UK, who release Guidelines which provide up-to-date evidence-based guidance on the diagnosis and treatment of haematological diseases.

BMS: Biomedical scientists test samples from patients, to support doctors and healthcare professionals in the diagnosis and treatment of disease.

CMV: Cytomegalovirus, a common virus that belongs to the herpes family of viruses.

DATIX: NHS Ayrshire and Arran’s web based incident reporting and risk management system.

EDD: Estimated due date

HEV: Hepatitis E Virus

HLA: Human Leucocyte Antigen system or complex is a gene complex encoding the major histocompatibility complex (MHC) proteins in humans.

HSCT: Haematopoietic Stem Cell Transplant - involves the intravenous infusion of autologous or allogeneic stem cells collected from bone marrow, peripheral blood, or umbilical cord blood to re-establish hematopoietic function in patients whose bone marrow or immune system is damaged or defective.

HTC: Hospital Transfusion Committee promotes the highest standards of transfusion practice throughout NHS Ayrshire and Arran

HTT: Hospital Transfusion Team manage the day-to-day business of Blood Transfusion within the hospital.

IgA: Immunoglobulin A, an antibody which plays a crucial role in immune function.

IUT: Intrauterine transfusions are red cells for prevention and treatment of fetal anaemia due to haemolytic disease of the fetus and newborn (HDFN) or parvovirus infection.

JPAC: Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee.

K+: Potassium is the major cation inside cells and is hugely important for regulating heartbeat and muscle function. It forms the other half of the electrical pump that keeps electrolytes in balance and allows conductivity between cells

LIMS: Laboratory information management system

NAIT: Neonatal alloimmune thrombocytopenia is a disease that affects fetuses and newborns, in which the platelet count is decreased (thrombocytopenia).

SABRE: Serious Adverse Blood Reactions and Events, which is the MHRA's online system for reporting blood safety incidents.

SABTO: The Safety of Blood, Tissues and Organs Committee advises UK ministers and health departments on the most appropriate ways to ensure the safety of blood, cells, tissues and organs for transfusion/transplantation.

SHOT: Serious Hazards of Transfusion is the UK’s independent, professionally-led haemovigilance scheme.

SNBTS: Scottish National Blood Transfusion Service.

SOT: Solid organ transplant.

T-activation: The most common acquired poly-agglutination, especially in children and infants, caused by exposure of RBC antigens after infections.

TA-GvHD: Transfusion associated Graft versus host disease is a rare complication of blood transfusion, in which the donor T lymphocytes mount an immune response against the recipient's lymphoid tissue.

v-CJD: Variant Creutzfeldt Jacobs Disease causing Transmissible spongiform encephalopathies.

This guideline has been assessed using the NHS Ayrshire & Arran standard impact assessment process document.