Blood Transfusion Reactions

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also separate article Blood Products for Transfusion.

Blood transfusion can be life-saving and provides great clinical benefit to many patients but it is not without risks:[1]

  • Immunological complications.
  • Errors and 'wrong blood' episodes (UK data from Serious Hazards of Transfusion (SHOT)) suggests an error incidence of 11.4/100,000 components transfused).[2]
  • Infections (bacterial, viral, possibly prion).
  • Immunomodulation.
  • Litigation.

Growing awareness of avoidable risk, and improved reporting systems have led to a culture of better safety procedures as well as steps to minimise the use of transfusion. However, the 2009 SHOT report includes analysis of 13 transfusion-related deaths (1 death considered directly attributable to transfusion and 12 deaths where transfusion was considered contributory) and, whilst transfusion-related mortality has continued to fall, avoidable, serious morbidity due to transfusion, such as that incurred by ABO incompatibility, remains persistent and may even be on the increase.[2]

Early complications of transfusion are rare, occurring in less than 1 in 1,000 transfusions, but tend to be more severe.[4]

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Acute haemolytic transfusion reaction

  • Incompatible transfused red cells react with the patient's own anti-A or anti-B antibodies or other alloantibodies (eg anti-rhesus (Rh) D, RhE, Rhc and Kell) to red cell antigens. Complement can be activated and may lead to disseminated intravascular coagulation (DIC).
  • Infusion of ABO incompatible blood almost always arises from errors in labelling sample tubes/request forms or from inadequate checks at the time of transfusion. Where red cells are mistakenly administered, there is about a 1 in 3 risk of ABO incompatibility and 10% mortality with the severest reaction seen in a group O individual receiving group A red cells.
  • Non-ABO red cell antibody haemolytic reactions tend to be less severe but the Kidd and Duffy antigens also activate complement and can cause severe intravascular haemolysis.

Infective shock

  • Bacterial contamination of a blood component is a rare but severe and sometimes fatal cause of transfusion reactions.
  • Acute onset of hypertension or hypotension, rigors and collapse rapidly follows the transfusion.
  • 3 UK cases of bacterial contamination of blood products during 2008-2009 were confirmed by SHOT.[2]
  • Platelets are more likely to be associated with bacterial contamination than red cells as they are stored at a higher temperature.

Transfusion-related acute lung injury (TRALI)

  • TRALI is a form of acute respiratory distress due to donor plasma containing antibodies against the patient's leukocytes.
  • Transfusion is followed within 6 hours of transfusion by the development of prominent nonproductive cough, breathlessness, hypoxia and frothy sputum.[5] Fever and rigors may be present.
  • CXR shows multiple perihilar nodules with infiltration of the lower lung fields.
  • Implicated donors are usually multiparous women (who are more likely to have become alloimmunised) and should be removed from the blood panel where possible. Gas exchange was significantly worse after transfusion of female but not male donor blood products in one study of high plasma volume transfusions in the critically ill.[6]

Fluid overload

  • This occurs when too much fluid is transfused or too quickly, leading to pulmonary oedema and acute respiratory failure.
  • Patients at particular risk are those with chronic anaemia who are normovolaemic or hypervolaemic and those with symptoms of cardiac failure prior to transfusion.
  • These patients should receive packed cells rather than whole blood via slow transfusion, with diuretics if required.

Non-haemolytic febrile reactions to transfusion of platelets and red cells

  • Fevers (>1°C above baseline) and rigors may develop during red cell or platelet transfusion due to patient antibodies to transfused white cells.
  • This type of reaction affects 1-2% of patients.
  • Multiparous women and those who have received multiple previous transfusions are most at risk. Reactions are unpleasant but not life-threatening. Usually symptoms develop towards the end of a transfusion or in the subsequent 2 hours. Most febrile reactions can be managed by slowing or stopping the transfusion and giving paracetamol.

Severe allergic reaction or anaphylaxis

  • Allergic reactions occur when patients have antibodies that react with proteins in transfused blood components.
  • Anaphylaxis occurs where an individual has previously been sensitised to an allergen present in the blood and on re-exposure, releases immunoglobulin E (IgE), or IgG, antibodies. Patients with anaphylaxis become acutely dyspnoeic due to bronchospasm and laryngeal oedema and may complain of chest pain, abdominal pain and nausea.
  • Individuals with severe IgA deficiency may develop antibody to IgA and, with repeated transfusion, are at high risk of allergic reaction.
  • Urticaria and itching are common within minutes of starting a transfusion.
  • Symptoms are usually controlled by slowing the transfusion and giving antihistamine and the transfusion may be continued if there is no progression at 30 minutes.
  • Pre-treatment with chlorphenamine should be given when a patient has experienced repeated allergic reactions to transfusion.

Symptoms or signs may occur after only 5-10 ml of transfusion of incompatible blood so patients should be observed closely at the start of each blood unit transfused.

Symptoms:

  • Feeling of apprehension or 'something wrong'.
  • Flushing.
  • Chills.
  • Pain at the venepuncture site.
  • Myalgia.
  • Nausea.
  • Pain in the abdomen, flank or chest.
  • Shortness of breath.

Signs:

  • Fever (rise of 1.5°C or more) and rigors.
  • Hypotension or hypertension.
  • Tachycardia.
  • Respiratory distress.
  • Oozing from wounds or puncture sites.
  • Haemoglobinaemia.
  • Haemoglobinuria.
  • Where a serious acute transfusion reaction is suspected, stop the transfusion and take down the donor blood and send back to the blood bank with notification of event.
  • To detect a haemolytic reaction, send post-transfusion blood (for FBC and clotting, repeat type and crossmatch, antibody screen and direct Coombs' test) and urine specimen (for detection of urinary haemoglobinuria) from the transfusion recipient.
  • Where an anaphylactic reaction is suspected, seek advice. Usual investigations require clotted blood samples and include serum Ig levels, HLA antibody investigations and mast cell tryptase.
  • Where bacterial contamination is suspected, send blood cultures from patient and bag remnants.
  • If the patient is dyspnoeic, obtain blood gases, CXR and central venous pressure (CVP) reading. Where TRALI is suspected, send anti-leukocyte antibody investigations.
Type of reaction Investigation findings
Acute haemolytic reactions
  • Visual inspection of centrifuged plasma - pink-red discolouration (haemoglobinaemia) where significant intravascular haemolysis.
  • Visual inspection of centrifuged urine - red discolouration due to haemoglobinuria.
  • Retype donor and recipient red blood cells (RBCs) - discrepancy suggests that the transfusion has been mismatched and blood samples mixed up.
  • Direct antiglobulin (Coombs') test (DAT) - ABO-related acute transfusion reactions usually cause a positive DAT test.
  • Evidence of increased RBC destruction, eg fall in Hb, rise in lactate dehydrogenase (LDH), rise in bilirubin.
  • May be evidence of DIC.
  • Negative blood cultures.
Febrile non-haemolytic reactions
  • Visual inspection of recipient's plasma and urine is normal.
  • Concordant retyping and negative DAT test.
Allergic and anaphylactic reactions
  • Do not usually cause an increased number of eosinophils in subsequent white blood cell (WBC) differentials.
  • Need to demonstrate anti-IgA in a pretransfusion sample of recipient's serum or plasma to establish the diagnosis.
  • Mast cell tryptase can be useful to differentiate anaphylactoid from allergic reactions.
TRALI
  • Blood gases - hypoxaemia.
  • CXR - bilateral lung infiltrates.
  • FBC frequently shows leukopenia and eosinophilia.
  • Investigate donor HLA and HNA antibody status.
Graft versus host disease (GvHD)
  • Pancytopenia.
  • Abnormal LFTs.
  • Deranged U&Es where diarrhoea.
Transfusion transmitted bacterial infection Blood cultures positive and congruent for both donor and recipient blood.
  • Where the only feature is a rise in temperature of <1.5°C from baseline or urticaria, recheck that the correct blood is being transfused, give paracetamol and antihistamine, reset the transfusion at a slower rate and observe more frequently.
    Whilst fever or rigors are not uncommon in response to a transfusion and may represent a non-haemolytic febrile reaction, they may also be the first sign of a severe adverse reaction.
  • Where the reaction is more severe:
    • Stop the transfusion and call a doctor urgently to review the patient.
    • Vital signs (temp, BP, pulse, respiratory rate, O2 saturation levels or blood gases) and respiratory status (dyspnoea, tachypnoea, wheeze and cyanosis) should be checked and recorded.
    • Check the patient's identity and recheck against details on blood unit and compatability label or tag.
  • Initial management where ABO incompatibility is suspected is to:
    • Keep the intravenous (IV) line open with saline.
    • Give oxygen and fluid support.
    • Monitor urine output, usually following catheterisation. Maintain urine output at more than 100 ml/hour, giving furosemide if this falls.
    • Consider inotrope support if hypotension is prolonged.
    • Treat DIC appropriately - seek expert advice early and transfuse platelets/fresh frozen plasma (FFP) guided by the coagulation screen and bleeding status.
    • Inform the hospital transfusion department immediately.
  • Where another haemolytic reaction or bacterial infection of blood unit is suspected:
    • Send haematological and microbiological investigations as outlined above.
    • General supportive management is as for ABO incompatibility.
    • Start broad-spectrum antibiotics if bacterial infection is considered likely. If expert microbiological advice is not immediately available, current guidance is to follow local neutropenic sepsis protocols.
    • Involve haematology and intensive care at an early stage.
  • Where anaphylaxis or severe allergic reaction is suspected:
    • High flow oxygen and nebulised salbutamol by facemask.
    • Give chlorphenamine 10-20 mg by slow IV injection.
    • Where there is severe hypotension, give adrenaline 0.5-1 mg intramuscularly (IM) and repeat every 10 minutes until improvement occurs.
    • Call the anaesthetist if there is difficulty maintaining the airway.
  • Where TRALI is suspected:
    • Seek expert help.
    • Give high-concentration oxygen, IV fluids and inotropes (as for acute respiratory distress syndrome).
    • Monitor blood gases, serial CXR and CVP/pulmonary capillary pressure.
    • Ventilation may be urgently required - discuss with ICU.
    TRALI improves over 2-4 days in over 80% cases with adequate ITU management and respiratory support.

  • Where fluid overload is suspected:
    • Give furosemide IV and high-concentration oxygen.

Delayed haemolysis of transfused red cells

  • In those who have previously been immunised to a red cell antigen during pregnancy or by transfusion, the level of antibody to the blood group antigen may be so low as to be undetectable in the pre-transfusion sample.
  • However, after transfusion of red cells bearing that antigen, a rapid, secondary immune response raises the antibody level drastically leading to the rapid destruction of transfused cells.
  • 5-10 days post-transfusion, patients present with fever, falling Hb (or unexpectedly poor rise in Hb), jaundice and haemoglobinuria.
  • A rise in bilirubin and positive direct antiglobulin test (DAT) will also be present.

Development of antibodies to red cells in patient's plasma (alloimmunisation)

  • Transfusion of red cells of a different phenotype to the patient's will cause alloimmunisation - for example, development of anti-RhD in RhD-negative patients who have received RhD-positive cells.
  • This is dangerous if the patient later receives a red cell transfusion, and can cause haemolytic disease of the newborn (HDN).

Development of antibodies that react with antigens of white cells or platelets

  • Transfusing red cells of a different phenotype to the patient's can also cause the development of leukocyte and/or platelet antibodies. This can cause non-haemolytic febrile transfusion reactions in the future.
  • The use of leukocyte-depleted red cells and platelets reduces the risk.

Post-transfusion purpura

  • This is a rare but serious complication caused by platelet-specific alloantibodies, more often seen in female transfusion recipients.
  • It usually occurs 5-9 days following transfusion.
  • Bleeding associated with a very low platelet count develops.
  • High-dose IV Ig is the current treatment of choice.

Graft versus host disease (GvHD)

  • This is a rare complication of transfusion, caused by T-lymphocytes.
  • Immunodeficient patients, especially allogenic bone marrow recipients and fetuses receiving intrauterine transfusions, are at greatest risk.
  • Transfusion-associated GvHD is almost always fatal (mortality rate 75-90%) and there is no effective treatment.
  • Acute GvHD begins between day 4 and day 30 following transfusion, with high fever and diffuse erythematous skin rash progressing to erythroderma, diarrhoea and abnormal liver function. Patients deteriorate with bone marrow failure and death occurs through overwhelming infection.

Transfusion-associated GvHD is preventable with the irradiation of cellular blood products. Patients requiring irradiated blood include:

  • Allograft bone marrow and stem cell recipients (for at least 6 months and some centres recommend indefinitely).
  • Patients who have in the past received purine analogue treatment.
  • Patients with Hodgkin's disease.
  • Patients with congenital cellular immunity deficiency.

They should be given an information leaflet and card informing them of their need for irradiated blood and must inform any clinical staff dealing with them in the future.

Iron overload

  • Each unit of blood contains 250 mg of iron and those receiving red cells over a long period may develop iron accumulation in cardiac and liver tissues.
  • Chelation therapy (with desferrioxamine) is used to minimise iron accumulation in those most at risk.

Infection

  • The risk of HIV, hepatitis B or hepatitis C from transfusion is now extremely small (1 in 4 million for HIV, 1 in 100,000 for hepatitis B and less than 1 in 400,000 for hepatitis C). However, prior to effective tests and screening of blood donors and products, significant numbers were infected and this should make us wary.
    Since there is always the potential for unrecognised or unknown infection to be spread via transfusion, all non-essential transfusions should be avoided.
  • Locally non-endemic infection such as human T-cell leukaemia virus type 1 (HTLV-1) and type 2 (HTLV-2), West Nile virus, malaria and Trypanosoma cruzi (causing Chagas' disease) may be transmitted by transfusion but donor selection procedures have limited the risk.
  • In the UK, variant Creutzfeldt-Jakob disease (vCJD) has caused great concern as it is thought that the infection is transmissible by blood transfusion. To date, three possible cases of transfusion-borne vCJD have been reported in the UK. Patients thought to have received vCJD-implicated plasma products have been contacted and should inform anyone giving them medical, surgical or dental treatment and should not donate blood, tissue or organs.[10]

Immunomodulation[11]

Concerns have been raised that tumour recurrence rates and postoperative infection rates are raised post-transfusion. However, clinical trials comparing recipients of autologous or leukocyte-depleted red cells and those receiving allogenic or non-leukocyte-depleted red cells found no difference in these outcomes.

  • All suspected transfusion reactions should be reported immediately to the local hospital transfusion department in case blood packs have been accidentally transposed and another patient is at immediate risk.
  • Transfusion reactions should be prominently recorded in the patient's clinical notes.
  • All transfusion reactions should be reviewed by the hospital's transfusion committee.
  • UK and European law requires that adverse reactions associated with licensed plasma derivatives or blood products be centrally reported. This currently occurs via an online system, Serious and Adverse Blood Reactions and Events (SABRE), linked to the UK Medical and Healthcare products Regulatory Agency (MHRA).[12]
  • Nationally, Serious Hazards of Transfusion (SHOT) is the UK's confidential, voluntary reporting system for serious events following transfusion of blood components and autologous transfusion. The body produces annual reports highlighting systemic problems and making recommendations to improve patient safety.

Reducing transfusion errors

  • Introduction of robust hospital transfusion protocols.
  • Training for all staff involved in blood administration/taking samples for cross-matching, including locum and agency staff.
  • An understanding of transfusion medicine should be a core curricular component for all doctors in training.
  • Improved information technology - use of a unique barcode on the patient's wristband/blood sample and prepared blood.
  • Appointing specialist transfusion practitioners - roles include development and evaluation of transfusion protocols and guidelines; facilitation of audit and improving blood ordering and administration systems; education of staff and patients about benefits and risks of blood transfusion, and sometimes direct involvement in near patient testing and cell salvage techniques.

Reducing unnecessary transfusion

  • Transfusion risks related to the use of allogenic blood can be eliminated by the use of autologous blood (where patients collect and store their own blood for use in planned surgery). This is not risk-free however.
  • Similarly, 'directed donation' (from family or friends) is discouraged as there is no evidence that these are safer and there are higher incidences of complications such as transfusion-associated GvHD in related individuals.
  • Ensuring that blood products are only used when the patient is judged more likely to benefit than be harmed by a transfusion.
  • Base prescribing decisions on the best available clinical guidelines modified according to individual circumstance. Always record the indication for giving blood in the patient's notes.
  • The need for transfusion can be reduced by stimulating red cell production with erythropoietin, reducing surgical bleeding with drugs such as aprotinin or surgical techniques such as hypotensive surgery, use of fibrin guns and sealants, allowing more time in theatre to achieve secure haemostasis and sometimes re-using the patient's lost blood (cell salvage).
  • Changing procedures such as checking for and correcting anaemia prior to planned surgery, stopping anticoagulants and antiplatelet drugs before surgery, minimising the amount of blood taken for laboratory samples and using a simple protocol to guide when Hb should be checked and when red cells should be transfused.
  • Accepting a lower Hb concentration as a trigger for transfusion. In the past, a trigger of 10 g/dL was standard but evidence suggests that in the critically ill (who are stable haemodynamically and not actively bleeding) aiming to maintain Hb concentration between 7-9 g/dL was at least equivalent to, if not better than, aiming for 10-12 g/dL. The only exceptions are thought to be in the elderly and in those with cardiac disease, where a safer target is over 9 g/dL.
  • Accepting smaller transfusions to just bring Hb concentration over the trigger level.
Currently there is no legal requirement in the UK to consent patients formally prior to transfusion of blood products, with use of consent forms, etc.[3] However, it is good practice to discuss:
  • The need for a blood transfusion and probable benefits.
    • Where blood loss is acute and severe, eg following an operation or accident, and the body is unable to compensate quickly, blood transfusion offers rapid relief of symptoms and can be life-saving.
    • Where there is severe, symptomatic anaemia that is resistant to other treatments.
    • To enable other medical or surgical procedures to be done safely.
  • Risks associated with blood transfusion:
    • Risks are small - the largest is of being given the wrong blood; however, multiple checks are taken to avoid this from happening.
    • The risk of infection from a blood infection is very small but not possible to eliminate.
  • Alternatives - patients may wish to discuss other options such as oral iron therapy or autologous transfusion.
  • Reducing the need for blood transfusion - with elective procedures:
    • Eat a well-balanced diet prior to the operation.
    • Check whether iron supplements are advisable.
    • Check whether/when aspirin, warfarin or other anticoagulants should be stopped.
Any patient judged competent who chooses not to accept a transfusion needs to be treated with respect and sensitivity, acknowledging their values, beliefs and cultural background. Jehovah's Witnesses are encouraged to carry documentation detailing their wishes about any future medical intervention and medical staff must take full account of this. Where refusing blood or blood components, they should sign the appropriate form, indicating an informed refusal.

Further reading & references

  1. Regan F, Taylor C; Blood transfusion medicine. BMJ. 2002 Jul 20;325(7356):143-7.
  2. SHOT annual report and summary 2009
  3. Handbook of Transfusion Medicine, UK Blood Transfusion and Tissue Transplantation Services (Jan 2007)
  4. Eder AF, Chambers LA; Noninfectious complications of blood transfusion. Arch Pathol Lab Med. 2007 May;131(5):708-18.
  5. Holness L, Knippen MA, Simmons L, et al; Fatalities caused by TRALI. Transfus Med Rev. 2004 Jul;18(3):184-8.
  6. Gajic O, Yilmaz M, Iscimen R, et al; Transfusion from male-only versus female donors in critically ill recipients of high plasma volume components. Crit Care Med. 2007 Jul;35(7):1645-8.
  7. Leeds and Bradford NHS Pathology Partnership; Blood Transfusion Reactions, 2007
  8. Minimum standards for investigation of transfusion related adverse reactions; based on SHOT guidance, Goodhope.org
  9. Sandler SG et al; Transfusion Reactions, eMedicine, Nov 2009
  10. Bird SM; Attributable testing for abnormal prion protein, database linkage, and blood-borne vCJD risks. Lancet. 2004 Oct 9-15;364(9442):1362-4.
  11. Raghavan M, Marik PE; Anemia, allogenic blood transfusion, and immunomodulation in the critically ill. Chest. 2005 Jan;127(1):295-307.
  12. Serious Adverse Blood Reactions and Events (SABRE), Medicines and Healthcare products Regulatory Agency's (MHRA) online reporting system

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Chloe Borton
Current Version:
Document ID:
292 (v4)
Last Checked:
20/04/2011
Next Review:
18/04/2016