Patients receiving blood transfusions can die if errors are made and if the signs of a severe reaction are not recognised and acted on at an early stage
Blood transfusion reactions are rare and vary in the degree of harm they cause the patient. In some cases, it may be clear on visual examination that a patient is having a severe reaction to a blood component; however, it may not be clear in all situations, especially if the patient is already unwell. This article focuses on how to recognise a reaction to a blood component, manage that reaction, and inform the relevant staff and organisation. It also discusses how transfusion safety can be improved.
Citation: Watson D, Denison C (2014) Blood transfusion 4: recognising and managing transfusion reactions. Nursing Times; 110: 39, 18-21.
Authors: Denise Watson is regional lead, Patient Blood Management Team at NHS Blood and Transplant, Newcastle; Clare Denison is Patient Blood Management practitioner at NHS Blood and Transplant, London.
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The Serious Hazards of Transfusion (SHOT) scheme was established in 1996 to improve transfusion safety by monitoring adverse events and reactions. In its 2013 review, there were 3,568 incident reports, with nine reports of ABO-incompatible red cell transfusions, four of which were classified as “never events” (that is, the reaction resulted in serious harm or death and could have been prevented) (Bolton-Maggs et al, 2014). In 2013, 99.5% (182/183) of NHS trusts/health boards were registered to report to SHOT directly or indirectly (Bolton-Maggs et al, 2014).
It is important that hospital transfusion teams (HTTs) report transfusion errors and near misses to SHOT. They should be treated with the same level of concern as all other serious incidents and should be fully investigated for root causes and corrective and preventive actions applied.
Serious transfusion reactions must be reported to the Medicines and Healthcare products Regulatory Agency through the Serious Adverse Blood Reactions and Events reporting portal, as mandated under the 2005 Blood Safety and Quality Regulations. Only actual incidents should be reported to MHRA; it does not accept near miss reports.
Transfusion reactions can occur:
- Within 24 hours of a transfusion (acute reactions);
- More than 24 hours after a transfusion (delayed reactions).
As reactions can occur several days after transfusion, the British Committee for Standards in Haematology’s Guideline on the Administration of Blood Components (Harris et al, 2009) recommends patients discharged within 24 hours of having a transfusion are given a contact card giving them 24-hour access to clinical advice.
Fig 1 shows the times between transfusion and recognition of a delayed reaction for cases reported to SHOT in 2013 (Bolton-Maggs et al, 2014).
Type and causes of transfusion reactions
Acute haemolytic transfusion reaction
Acute haemolytic transfusion reaction occurs when a transfusion of incompatible red cells causes an acute severe clinical reaction between the transfused red cells and usually, but not always, the patient’s own anti-A or anti-B antibodies. In rare situations, it can be caused by other antibodies (Jones and Heyes, 2014).
Patients who are conscious often become very unwell within the first few minutes of transfusion, complaining of flushing, loin and abdominal pain, and “a feeling of impending doom” (Norfolk, 2013). In patients who are unconscious, the first indication of a reaction may be tachycardia, hypotension or bleeding into the skin or from needle wounds, which may resemble bruising.
Febrile reactions can vary in severity and occur because the antigens on the blood component react with the patient’s white cell antibodies. These reactions have become less common since the introduction of universal leucodepletion (filtering) of blood components by NHS Blood and Transplant (Jones and Heyes, 2014).
Characterised by fever, and sometimes accompanied by shivering, muscle pain and nausea, febrile reactions can occur up to two hours after completion of the transfusion. They can be classified as:
- Mild: pyrexia of >38°C, but <2°C rise from baseline;
- Moderate: pyrexia of >2°C above baseline or >39°C, or rigors and/or myalgia (muscle pain).
Allergic reactions include anaphylaxis, urticaria or a rash, and can be mild, moderate or severe. Shock or severe hypotension associated with wheeze (broncho-spasm), stridor from laryngeal oedema or swelling of the face, limbs or mucous membranes (angioedema) strongly suggest anaphylaxis.
Symptoms of mild reactions are confined to itching (pruritus) and/or skin rash (“nettle rash” or hives) with no changes in vital signs. They often improve if the transfusion is slowed and antihistamine administered orally or intravenously.
Transfusion-transmitted infection occurs as a result of bacterial or viral contamination of blood components. Bacterial contamination is more common with platelets as they are stored at 22°C, which can lead to greater bacterial proliferation. However, viral contamination can be present in any blood component.
Transfusion of a blood component contaminated with bacteria often causes an acute severe reaction soon after the transfusion has started. Initially, this may be indistinguishable from an acute haemolytic reaction or severe allergic reaction. Inspection of the pack may show abnormal discolouration, aggregates or an offensive smell, but many contaminated packs appear normal. Typical symptoms and signs include rigors, fever (usually >2°C above baseline), hypotension and rapidly developing shock and impaired consciousness.
Blood cultures should be taken from the patient and treatment started immediately with an intravenous, broad-spectrum antibiotic combination covering Gram-negative and Gram-positive bacteria (the local empirical antibiotic regimen used in patients with neutropenic sepsis is appropriate) (Norfolk, 2013).
Implicated units should be sealed to avoid leakage or contamination and returned to the transfusion laboratory for investigation. The blood transfusion centre must be contacted (usually by the hospital transfusion laboratory staff) so any associated components from the implicated donor can be urgently identified and withdrawn from transfusion laboratories.
Transfusion-related acute lung injury
Transfusion-related acute lung injury is caused by antibodies in the donor plasma that react with the patient’s white cells (neutrophils and monocytes) or pulmonary endothelium (cells that line the lungs); this reaction is more common with plasma-rich components such as fresh frozen plasma (FFP). Inflammatory cells are sequestered in the lungs, causing leakage of plasma into the alveolar spaces. This results in non-cardiogenic pulmonary oedema.
Most cases present within two hours of transfusion (maximum within six hours) with severe breathlessness and a productive cough of frothy pink sputum. It is often associated with hypotension (due to loss of plasma volume), fever, rigors and transient peripheral blood neutropenia or monocytopenia (temporarily reduced white blood cell count).
Transfusion-associated circulatory overload
Too much blood being transfused too quickly - especially to vulnerable groups including neonates or older people - can lead to acute left ventricular failure. Typical features include acute respiratory distress, tachycardia, hypertension and evidence of a positive fluid balance.
Transfusion-associated dyspnoea is characterised by respiratory distress within 24 hours of transfusion that does not meet the criteria of transfusion-related acute lung injury, transfusion-associated circulatory overload or allergic reaction. Any underlying condition that could have caused the respiratory distress should be ruled out.
Delayed haemolytic transfusion reactions
If a patient has an antibody that may not have been detectable by routine blood testing, transfusing a unit of red cells that contain the corresponding antigen can cause a reaction. Haemolysis (breakdown of red blood cells) becomes clinically apparent up to 14 days after a transfusion; signs may include a falling haemoglobin concentration or failure to achieve the expected increment (a rise in Hb level after transfusion), jaundice, fever and occasionally haemoglobinuria (presence of haemoglobin in the urine) or acute renal failure.
Transfusion-associated graft-versus-host disease
Residual white cells in the transfused blood components can replicate and mount an immune response in patients who are immunocompromised. Symptoms classically occur 7-14 days (maximum 30 days) after a transfusion with fever, skin rash, diarrhoea, disturbed liver function and worsening bone-marrow aplasia; the condition is almost always fatal.
Post-transfusion purpura occurs in patients who have a platelet-specific antibody that leads to a significant drop in platelet count after transfusion. Affected patients develop a low platelet count and bleeding occurs 5-12 days after a transfusion of red cells. Bleeding may occur from the gastrointestinal tract and epistaxis is common. The mortality rate is 9%; death results from intracranial haemorrhage (Taylor, 2008).
Recognising a transfusion reaction
In some cases, it is clear on visual examination that a patient is having a reaction to a blood component, but this is not always the case, especially if a patient is already very ill. A reaction can be suspected from a change in the patient’s vital signs or on the basis of any sudden unexpected change/deterioration in their condition during or immediately after the transfusion. It is also possible for a transfusion reaction to be delayed and become apparent more than 24 hours following the transfusion.
The BCSH (2009) guidance recommends that observations are taken and recorded as follows:
- Pulse rate, blood pressure, temperature and respiratory rate no more than 60 minutes before the blood transfusion is started;
- Pulse rate, blood pressure and temperature 15 minutes after the start of each blood component - if these readings are significantly different from the baseline observations, the respiratory rate should also be included;
- Pulse rate, blood pressure and temperature no more than 60 minutes after the end of the transfusion.
These recommendations are the minimum observations that should be recorded, and local policies may differ. If a patient deteriorates or a transfusion reaction is suspected, the transfusion should be stopped, observations must be taken more frequently and the patient will require immediate medical attention. Box 1 outlines what to do if a reaction is suspected.
Box 1. Responding to a suspected transfusion react
All transfusion reactions need to be managed. If you suspect a reaction:
- Stop the transfusion
- Take and record the patient’s vital signs
- Seek medical advice immediately and inform the hospital transfusion laboratory
The key step to treating anaphylaxis is to use the ABCDE (Airway, Breathing, Circulation, Disability, Exposure) approach (Resuscitation Council (UK), 2008).
A flow diagram for the recognition, initial management and subsequent management and investigations can be found in the British Committee for Standards in Haemotology’s Guideline on the Investigation and Management of Acute Transfusion Reactions (Tinegate et al, 2012).
Minimising transfusion reactions
Some transfusion reactions cannot be foreseen or avoided as antibody levels rise and fall and may not always be detected during the crossmatch process. However, transfusion-associated circulatory overload may be avoided by considering the patient’s risk factors, as well as the volume, rate and timing of transfusions.
For example, in patients who are at risk, practitioners can slow down the rate of infusion while ensuring the blood or blood component is transfused within acceptable time limits - that is, no more than four hours after it was removed from the controlled temperature storage. Clinicians should also consider the administration of prescribed diuretics to prevent fluid overload.
Incorrect blood component transfused (IBCT) errors resulting from misidentification and human error are all preventable. These may lead to an acute haemolytic transfusion reaction, which, in some instances, can be fatal. SHOT describes the category of IBCT as: “episodes where a patient was transfused with a blood component that was intended for another patient, with a component of different type or one which was incorrect in terms of its specification”.
Although some of these incidents occur as a result of laboratory errors, many are due to errors occurring in the clinical area, such as sampling resulting in “wrong blood in tube” and bedside blood administration errors.
Table 1 shows the number of wrong blood components transfused in 2013. Of the 247 reports where patients received an IBCT, a wrong component was transfused in reports, while five were identified before transfusion; in 190 reports, the patient’s specific requirements were not met (Bolton-Maggs et al, 2014).
Failure to identify the patient correctly (positive patient identification) is often implicated as a root cause of IBCT errors. Some hospitals have introduced IT systems into clinical areas, often using bar-code wristbands and scanners, to help improve the safety of the final bedside administration procedures.
Most laboratory systems indicate to laboratory staff when different blood groups for the same patient are identified (that is, when the patient’s blood group has previously been found to be a different type to the current sample received), or when specific requirements are needed, such as irradiated blood components for patients who are immunocompromised. However, while IT systems can help to alert staff to errors, they do not replace the manual checking process and health professionals should not rely on them to prevent human errors.
Reporting transfusion reactions
All suspected transfusion reactions must be reported immediately to the hospital transfusion laboratory and to a member of the HTT so laboratory investigation and follow-up can begin. It may also be necessary for the HTT member to contact NHSBT to recall other blood components from the same donor.
All adverse events and reactions must be documented in the patient’s notes and formally reported via the hospital’s local risk management system. They must also be reported to a member of the HTT who will then investigate and if required report to SHOT and/or the MHRA. It is important to understand why the transfusion reaction has occurred to be able to reduce the risk of other reactions in the future.
In 2009, SHOT developed an action plan to improve local and national reporting (Taylor et al, 2010). It recommends:
- Establishing current level of reporting: how does your organisation’s reporting record compare with those of similar organisations?
- Give feedback to staff: do you provide/receive feedback after you have submitted a report?
- Focus on learning: has your patient care changed/improved as a result of reporting?
- Engage frontline staff: do you have safety champions on your ward?
- Make it easy to report: who should you report to and how?
- Make reporting matter: the aim of reporting is to improve safety rather than blame individuals.
It can be difficult to categorise a transfusion reaction in the early stages, but it is vital to be aware of all of the possible reactions so appropriate and timely treatment can be given.
All patients should be transfused in clinical areas where they can be directly observed and where practitioners have received up-to-date training on administering blood components and managing patients who have had a transfusion. This includes the emergency administration of anaphylaxis (Tinegate et al, 2012).
The 2009 SHOT report (Taylor et al, 2010) recommends a patient education campaign similar to those used for infection prevention and control. The Do You Know Who I Am? campaign aims to encourage patients receiving a blood transfusion (and other medical interventions) to ask staff “Do you know who I am?” before the intervention was carried out. Please ensure you know who your patient is before you transfusea blood component.
SHOT has produced advice for staff involved in transfusions:
- It is essential to check the patient’s identity before transfusing a blood component
- Observations must be taken and recorded before blood components are administered
- These should be compared with observations recorded during and at the end of a transfusion
- Transfusion reactions can occur immediately, within 24 hours of a transfusion or more than 24 hours after a transfusion
- Nurses should know the signs of a transfusion reaction, when to report signs, and how and to whom they should be reported
Bolton-Maggs PHB et al (2014) Annual SHOT Report 2013.
Harris A et al (2009) Guideline on the Administration of Blood Components.
Jones A, Heyes J (2014) Blood transfusion 2: processing, testing and selecting blood components. Nursing Times; 110: 37, 20-22.
Norfolk D (ed) (2013) Handbook of Transfusion Medicine. Norwich: Stationery Office.
Resuscitation Council (UK) (2008) Emergency Treatment of Anaphylactic Reactions: Guidelines for Healthcare Providers.
Taylor C et al (2010) Annual Report 2009. SHOT.
Taylor C et al (2008) Immunological complications of blood transfusion. Transfusion Alternatives in Transfusion Medicine; 10: 112-126.
Tinegate H et al (2012) Guidelines on the Investigation and Management of Acute Transfusion Reactions.