By pressing the 'Accept and continue' button, you indicate that you have read and consent to the Terms of Use.

Terms of Use

Purpose, scope and audience

Special Blood Components ("the app") aims to make it easy to learn about the correct use of irradiated and cytomegalovirus (CMV) negative blood components in patients with special transfusion requirements. It is designed for:

  • Doctors who prescribe and request blood transfusions.
  • Nurses and midwives who administer or prescribe transfusions.
  • Biomedical scientists who process blood requests.
  • Medical trainees who may be required to undertake any of the above.

Evidence base

The app is based on the British Committee for Standards in Haematology (BCSH) 2010 guidelines on the irradation of blood components and the 2012 position statement on the use of CMV negative blood components by the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO).

Disclaimer

The app was created during a PhD research project at the University of Edinburgh and is available for evaluation only. There may be inaccuracies in the content. Guidance may not be appropriate in all patient situations and local hospital policies may differ.

The app is not intended to be a substitute for local hospital guidelines, professional medical judgement, advice, diagnosis, or treatment. The app publishers, developers and contributors do not take any legal resposibility for harm resulting from the use of the app. Use your own critical judgement and always put patient safety first.

Data protection

The app is developed as part of a research project seeking to evaluate and improve the design of medical apps. The use of the app is therefore monitored using Google Analytics. To do this we store a browser cookie on your device. The following data is recorded:

  • Which pages you visit and for how long.
  • Information about your computing device (operating system, screen resolution, browser, IP address).
  • Your approximate geographical location (country, city).

This data is only available to the researchers, but analysis of the data may be presented in academic publications observing academic good practice, such as protecting confidentiality through pseudonymisation and anonymisation.

No warranty

THE APP IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE APP OR THE USE OR OTHER DEALINGS IN THE APP.

Accept and continue
Learn
What is the rationale for irradiated and CMV-negative blood components?
Indications
Which patients require irradiated and/or CMV-negative blood components?
QuickFind
Search across the app.
About the app
Find out more about this app.

Purpose, scope and audience

Special Blood Components ("the app") aims to make it easy to learn about the correct use of irradiated and cytomegalovirus (CMV) negative blood components in patients with special transfusion requirements. It is designed for:

Evidence base

The app is based on the British Committee for Standards in Haematology (BCSH) 2010 guidelines on the irradation of blood components and the 2012 position statement on the use of CMV negative blood components by the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO).

Design assumptions

The app was designed to meet short term informational needs and encourage deeper learning, by providing quick access to indications and information explaining the rationale behind them, as well as what can go wrong and how to prevent mistakes.

The traffic light system is used to communicate when special components are required (red), may be required (amber) or are unlikely to be required (green).

How to use the app

The app has three main sections, accessible from the home screen.

Authors

The Special Blood Components App is developed by Dr. Brian McClelland, a retired transfusion expert and editor of the fourth edition of the Handbook of Transfusion Medicine, and Karl Monsen, a PhD candidate at The University of Edinburgh. You can contact the authors at: specialstudy@optimalblooduse.eu

Contributors

The authors would like to acknowledge the support and contributions from (in alphabetical order):

Which patients require irradiated or CMV-negative blood components?

Press an indication to show details.

Indication Irradiation CMV-negative
Back to top

Glossary

Blood components, types of

Blood is separated into five components (HTM 2007, p.1):
1. Red cells
2. Platelets
3. White cells
4. Fresh frozen plasma (FFP)
5. Cryoprecipitate

These can be classified into cellular and non-cellular (plasma) components.

Cellular blood components

Platelets, red cells and white cells are cellular blood components that contain leucocytes (white cells). TA-GvHD and TT-CMV are both associated with cellular blood components.

Cellular blood components, even if leucodepleted, must be irradiated to deactivate any residual lymphocytes before transfusion to at-risk patients (BCSH 2010).

The only exception to this rule is cryopreserved red cells after deglycerolization, because these have been frozen and washed free of leucocytes (BCSH 2010, p42).

Monocytes, another type of white cell present in cellular blood components, can carry latent cytomegalovirus (CMV). For this reason it is recommended that cellular blood components are provided leucodepleted and CMV-negative to high risk patients (SaBTO 2012).

Cytomegalovirus, Transfusion-Transmitted (TT-CMV)

"Cytomegalovirus is a herpes virus that gives rise to chronic, persistent and, for the most part, asymptomatic infection in a majority of adults worldwide. More severe disease may occur in certain groups, such as foetuses, neonates and immunocompromised adults." (SaBTO 2012, p.1)

"Cytomegalovirus (CMV) infection can cause serious morbidity in immunocompromised CMV-negative patients. The risk can be minimised by the use of CMV-antibody-negative (seronegative) blood components. Leucocyte depletion also confers some protection since the virus is associated with white blood cells." (HTM 2007, p.41)

Read more about TT-CMV

CMV-negative blood

CMV-negative blood refers to blood collected from from donors who test negative for CMV antibody. CMV-negative components are indicated for patients at risk of TT-CMV infection.

First- or second-degree relatives

"The 'degree of relationship' describes the proportion of genes shared by two blood relatives. A person's first degree relative is a parent, sibling, or child. A first degree relative shares about half of their genes with the person." (NHS NGGEC no year)

"A second degree relative of a person is an uncle, aunt, nephew, niece, grandparent, grandchild or half- sibling. A second degree relative shares about one quarter of their genes with the person." (NHS NGGEC no year)

Graft versus Host Disease, Transfusion Associated (TA-GvHD)

"TA-GvHD is a very rare but usually fatal complication following transfusion of lymphocyte-containing blood components." (BCSH 2010, p.37)

"Transfused donor lymphocytes which are compatible with the recipient, but which recognise the recipient as foreign, can engraft and initiate TA-GvHD. Patients develop skin rash, diarrhoea and abnormal liver function, and deteriorate, with bone marrow failure and death from infection usually within two to three weeks of transfusion." (HTM 2007, p.41)

Read more about TA-GvHD

Irradiation, of blood cellular components

"The major technology for preventing TA-GvHD is irradiation of blood components to inactivate residual lymphocytes. Gamma rays and X-rays are similar in their ability to inactivate T lymphocytes in blood components at a given absorbed dose." (BCSH 2010, p. 41)

"In the UK, a minimum of 25 Gy is recommended, but with the dose to any bag in the container not exceeding 50 Gy. To ensure this dose distribution is achieved, consultation with supporting physicists is mandatory." (BCSH 2010, p. 41)

"For at-risk patients, all red cell, platelet and granulocyte concentrates should be irradiated except cryopreserved red cells after deglycerolization. It is not necessary to irradiate fresh frozen plasma, cryoprecipitate or fractionated plasma products." (BCSH 2010, p. 36)

Leucodepletion, universal

"With the introduction of universal leucodepletion in 1999, all red cells and platelets supplied through the UK blood services are leucocyte depleted." (SaBTO 2012, p.1)

"Removal of leucocytes to a level of less than one million per component by filtration or during collection of blood components by apheresis is normal practice in a number of EU countries. Advantages of leucodepletion include a marked reduction in alloimmunisation to HLA antigens and in the risk of infection by intracellular viruses such as cytomegalovirus. Leucodepletion of red cells may also be associated with improved outcomes in some groups of patients." (OBU 2010)

Non-cellular blood components (plasma)

Fresh frozen plasma, cryoprecipitate and fractionated plasma products are non-cellular blood components that do not contain white cells.

Non-cellular blood components do not need to be irradiated or provided as CMV negative, eventhough CMV can occur freely in plasma during active CMV infections (SaBTO 2012, p.2).

Learning Outline

Press 'Next' to continue or select a topic in from the list above.

Next Back Back to top

Learning Objectives

This section explains the rationale for using irradiated, leucodepleted and/or CMV-negative blood components to prevent TA-GvHD and TT-CMV infection. After reviewing the learning material you should be able to:

Learning Outline

Press 'Next' to continue or select a topic in from the list above.

Next Back Back to top

Transfusion-Associated Graft versus Host Disease (TA-GvHD)

TA-GvHD is a rare, almost universally fatal disease caused by the transfusion of cellular blood (red cells, platelets and granulocytes) components containing viable lymphocytes. The transfused donor lymphocytes engraft and attack the recipient, causing skin rash, diarrhoea, liver disease, bone marrow failure and death from infection often within two-three weeks of the transfusion (HTM 2007, p.41) (BCSH 2010, p.41), although the clinical picture may be longer in neonates.

Prevention and risk factors

TA-GvHD is prevented by exposing cellular blood components to a dose of 25-50 Gy of Gamma or X-ray irradiation, thus inactiving the donor lymphocytes that give rise to TA-GvHD (BCSH 2010, p.41). Only cellular blood components for patients at risk of TA-GvHD require irradiation. The risk of developing TA-GvHD depends on three factors (BCSH 2010, p.37):

Patients at risk of TA-GvHD

In most cases, the recipient's immune system is capable of detecting and destroying the donor lymphocytes before they engraft. This requires a competent immune system. Immunodeficient patients (whether congenital or as a result of immunosuppressive treatment) are therefore at risk of TA-GvHD and must receive irradiated cellular blood components.

Figure: Shared HLA between donor and recipient

TA-GvHD can also occur in immunocompetent recipients. If the donor and recipient share an HLA type, the recipient's immune system is unable to distinguish the donor lymphocytes from the body's own cells, allowing the donor lymphocytes to engraft (see figure above). Shared HLA haplotypes are much more likely to occur in the setting of directed donations from relatives than between random donors and recipients. Shared HLA types will also necessarily be present in the setting of HLA-matched transfusions. In these circumstances cellular blood components must be irradiated, even if the patient is immunocompetent.

Additionally, all granulocyte transfusions must be irradiated as they contain a high concentration of lymphocytes, cannot be leucodepleted and are often given to immunodeficient patients UKBTS 2012.

Leucodepletion reduces the risk of TA-GvHD

All platelets and red cells units are leucodepleted in the UK, significantly reducing the number of lymphocytes in these components. Leucodepletion was introduced as a vCJD (Variant Creutzfeldt-Jakob disease) risk reduction measure. It has also had unintended other beneficial effects including reducing the risk of TA-GvHD by reducing, and in some cases removing, viable lymphocytes from cellular blood components.

Only two cases of TA-GvHD have been reported in the UK following the introduction of universal leucodepletion in 1999, despite many hundred reports of patients at risk of TA-GvHD being transfused with non-irradiated cellular blood components (BCSH 2010, p.41). This suggests that leucodepletion is effective in reducing the risk TA-GvHD. However, leucodepletion is not a replacement for irradiation as it may not remove all viable lymphocytes and may occasionally fail (only a selection of all cellular components are tested for the efficacy of the leucodepletion).

Learning Outline

Press 'Next' to continue or select a topic in from the list above.

Next Back Back to top

Transfusion-Transmitted Cytomegalovirus (TT-CMV)

Cytomegalovirus (CMV) is a herpes virus that causes a chiefly asymptomatic infection in healthy people. About half the UK population is CMV positive and many blood donors carry the virus. The virus occurs freely in blood plasma during active infection and remains latent in monocytes following infection (SaBTO 2012, p.5).

Figure: CMV micrograph

Risk groups

CMV infection often goes unnoticed in immunocompetent patients, but it can be fatal or cause lifelong disability in fetuses, neonates and immunocompromised patients (SaBTO 2012, p.1). Neonatal mortality from CMV infection is 10-30% (higher in preterms) and the virus accounts for 12% of all sensorineural hearing loss and 10% of cerebral palsy (SaBTO 2012, p.4).

Prevention

CMV is a cell-associated virus and can be present in cellular blood components (red cells, platelets and granulocytes). TT-CMV infection is prevented by removing leucocytes from red cells and platelets through leucodepletion and by providing at risk patients with blood from donors who screen negative for CMV antibody (SaBTO 2012).

Leucodepletion

Leucodepletion is the removal of white cells, usually by filtration, from red cells and platelets. This process is particularly effective in removing monocytes, where latent CMV may be present (SaBTO 2012, p.2). Since 1999 all platelets and red cells produced in the UK are leucodepleted. Universal leucodepletion has significantly reduced the chance of TT-CMV infection, but not completely eliminated it and at risk patients should receive blood from CMV-negative screened donors (SaBTO 2012).

Who should receive CMV-negative blood?

CMV-negative blood is indicated for intra-uterine and neonatal transfusions (up to 28 days post expected date of delivery) (SaBTO 2012, p. 11). If a pregnant mother is infected or re-infected with CMV there is a high chance of transmission of the virus to the baby (SaBTO 2012, p. 6). Therefore, pregnant women, regardless of their CMV serostatus, who receive elective transfusions should receive CMV-negative blood (SaBTO 2012, p. 6). CMV-negative components are however not required during labour and delivery. If in an emergency during pregnancy CMV-negative blood is unavailable, CMV random (universally-leucodepleted in the UK) blood should be used instead (SaBTO 2012, p. 11). Finally, CMV-negative components should be provided to seronegative patients receiving granulocytes, as these cannot be leucodepleted (SaBTO 2012, p. 11).

For all other patients, including patients with HIV, organ transplant and haemopoetic stem cell transplant patients, the use of leucodepleted components provides adequate protection against TT-CMV (SaBTO 2012, p. 11). Further if such patients were to develop CMV disease, its diagnosis and treatment is much easier and more effective than in the fetal/neonatal setting.

Learning Outline

Press 'Next' to continue or select a topic in from the list above.

Next Back Back to top

Errors in the provision of special requirements

Between 2008 and 2012 more than five hundred mistakes involving irradiated and CMV negative blood components were reported to the Serious Hazards of Transfusion (SHOT) UK haemovigilance scheme (see figure). These were cases when blood components failed to be provided as irradiated and/or CMV negative to patients with special requirements according to guidelines. To put this in perspective, almost three million blood components are issued annually in UK (SHOT 2009, p.11), of which approximately 10% are irradiated (SHOT 2010, p.129).

Figure: Errors 2008-2012.

What are some of the causes for mistakes?

There are many underlying reasons for why special requirements fail to be provided to at-risk patients, as these SHOT cases illustrate (press to expand):

Poor knowledge of the indications

"The admitting doctor noted the past history of Hodgkin's disease but was not aware of the requirements for irradiated blood." (SHOT 2011, p.26)

Request form not filled out correctly

"A request form for blood components for a patient with CLL on fludarabine was completed by a haematology nurse, and checked and signed by a junior doctor who also prescribed the components. The need for irradiated blood was not indicated on the request form or the prescription." (SHOT 2008, p.46)

Failure to check medical record

"An elderly man was transfused 9 units of blood for chronic anaemia. Subsequently a haematology registrar found that he had been treated with cladarabine several years before." (SHOT 2012, p.32)

Shared patient care

"A patient was transferred from his primary hospital, where he had undergone a stem-cell transplant, to another hospital within the same Trust in order to access an ITU bed. [...] Irradiated components were not requested due to a lack of communication between the clinicians, and the laboratory records were separate from those at the originating hospital." (SHOT 2010, p.41)

Wrong blood component transfused

"No patient identification was taken to the blood fridge, and as a result the wrong unit of red cells was removed by a registered nurse and taken to the ward for an 81-year-old female patient with chronic lymphocytic leukaemia (CLL). On the ward another nurse administering the transfusion assumed that the checks had been completed, and because of this assumption no bedside checks were performed. The patient received non-irradiated group A D positive red cells, instead of irradiated O D positive red cells. The error was noticed when the patient asked whether the unit was irradiated. Consequently <50 mL was transfused." (SHOT 2008, p.31)

Incorrect use of warning flags

"A patient required irradiated blood because of previous chemotherapy. The transfusion laboratory had received notification of this special requirement and added the information to the LIMS. The special requirement flag was subsequently removed from the LIMS in error. From the time the flag was removed to the time it was discovered, the patient had received 15 units of red cells and 5 units of platelets that had not been irradiated." (SHOT 2012, p.56)

How can mistakes be prevented?

SHOT has made several recommendations aimed at reducing mistakes, including (press to expand):

Increase knowledge of special requirements

"All haematology units must devise specific educational programmes for all their staff members providing the rationale and indications for specialist components and this information should be accessible at the time of making the requests for blood components." (SHOT 2011, p.28)

"The importance of irradiation, and the rationale behind it should be emphasised during teaching of junior haematology and oncology doctors. This education is part of the curriculum for specialist trainees, but the junior pre-specialist doctors in these areas may remain ignorant despite being frequently called upon to order components." (SHOT 2008, p.26)

Ensure special blood components are ordered correctly

"Local mechanisms for ordering and prescribing components need to facilitate correct ordering, and remind clinical and laboratory personnel where possible." (SHOT 2011, p.26)

Educate patients who have special requirements

"Patients who require irradiated and other special products should be provided with an appropriate card [...] Patients with cards noting special requirements should be educated about their meaning and importance, in particular always to show these to clinical staff on admission to any hospital." (SHOT 2012, p.34)

Conduct thorough bedside checks

"The final 'bedside' check is the last opportunity to ensure that the correct unit or component has been collected for the patient receiving the transfusion. Complete and thorough bedside checks involving one or two staff members must be completed independently and without interruption. " (SHOT 2011, p.61)

"Every person in the transfusion process must perform rigorous identity checks at each point and ensure that the component collected is the one prescribed. The use of a transfusion checklist is recommended." (SHOT 2013, p.62)

Use warning flags with care

"Computer prompts/warnings/flags are a valuable tool for trying to prevent human error through 'slips'; but staff must also have the underpinning knowledge to understand and act appropriately to a warning." (SHOT 2012, p.7)

"The addition of these warnings/flags/notes is a manual procedure and is itself prone to error and should be controlled, for example, entered by one BMS and checked by a second." (SHOT 2012, p.51)

Learning Outline

Press 'Next' to continue or select a topic in from the list above.

Next Back Back to top

References

Links open in a new window.

Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) (2012) Position statement on cytomegalovirus tested blood components. Open

Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) (2012) Report of the Cytomegalovirus Steering Group Open

Bolton-Maggs, P (Ed) and Cohen, H (2012) on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2011 Annual SHOT Report. Open

Bolton-Maggs P (Ed), Poles D, Watt A, Thomas D and Cohen H (2013) on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2012 Annual SHOT Report.Open

Joint UKBTS / HPA Professional Advisory Committee (2012) Position Statement on Granulocyte Therapy. Revised by Edwin Massey, Simon Stanworth and Rebecca Cardigan at the request of the Standing Advisory Committee on Blood Components. Open

McClelland DBL (ed) (2007) Handbook of Transfusion Medicine, 4th Ed. Published in the UK by The Stationary Office. Open

McClelland DBL, Pirie E, Franklin IM (2010) for the EU Optimal Use of Blood Project Partners. The Optimal Blood Use Manual. Published by Scottish National Blood Transfusion Service. Open

Medical Subject Headings (2013) published by the U.S. National Library of Medicine, National Institutes of Health. Open

NHS National Genetics and Genomics Education Centre, glossary item "First-degree relative". Open

Public Health Image Library (PHIL), 1986, Centres for Disease Control and Prevention. Open

Taylor C, Cohen H, Jones H, et al (2008), on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2007 Annual SHOT Report. Open

Taylor C (Ed.), Cohen H, Mold D, Jones H, et al (2009), on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2008 Annual SHOT Report. Open

Taylor C (Ed.), Cohen H, Mold D, Jones H, et al (2010), on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2009 Annual SHOT Report. Open

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 Open

Learning Outline

Press 'Home' to return to the front screen or select a topic in from the list above.

Home Back Back to top

Search the app