27th May 2023

Transfusion reactions

Early recognition of a transfusion reaction is important. Vital signs are monitored closely during blood product transfusion. There is a wide differential diagnosis for severe acute reactions. Regardless of the cause, if a patient becomes unwell during a transfusion:

1. Stop the transfusion
2. Perform an ABCDE assessment and resuscitate the patient
3. Recheck the ID details of the patient, ID wristband and compatibility label of the blood component
4. Inspect the product for clumps or discolouration

For significant acute transfusion reactions (a temperature rise of >2°C or to >39°C or any additional symptoms apart from isolated rash)

5. Contact the hospital transfusion laboratory
6. Return the transfusion pack to the transfusion laboratory for further investigation
7. Investigations should include FBC, renal and liver function and a coagulation screen
8. If any concern about haemolysis, send a direct antiglobulin test (DAT), lactate dehydrogenase (LDH), haptoglobin, blood film and urinary haemosiderin.
9. If the patient is febrile, send blood cultures
10. If there is concern over anaphylaxis then administer IM adrenaline and send IgA level and serial mast cell tryptase levels at 0, 3 and 24 hours.

Serious adverse reactions and events will be reported to the Serious Hazards of Transfusion (SHOT) scheme and the Serious Adverse Blood Reactions and Events (SABRE) reporting system.

Haemolytic reactions

Acute haemolytic reaction

In ABO-incompatible red cell transfusion, a patient’s anti-A or anti-B antibodies cause rapid haemolysis of the transfused red cells and inflammatory cytokine release. Shock, acute renal failure and disseminated intravascular coagulation (DIC) may occur. ABO-incompatible red cell transfusion is almost universally fatal. Stringent safety checks when taking G&S samples, transporting blood products and carrying out blood product administration aim to avoid this ‘never event’. Patients become very unwell within minutes of transfusion with flushing, abdominal pain, a sense of impending doom, tachycardia, hypotension and may have signs of bleeding from needle wounds.

Delayed haemolytic transfusion reaction

Delayed haemolytic transfusion reactions (DHTR) can occur 1-14 days after transfusion in a patient who has been previously alloimmunised to a red cell antigen by blood transfusion or pregnancy.  This alloantibody may have fallen to an undetectable level and therefore may not be identified on the G&S antibody screen. DHTR should be suspected if the following occur:

• A falling haemoglobin/failure to increment
• Jaundice
• Fever
• Haemoglobinuria

A haemolysis screen should be performed. Treatment is supportive, but the antibody history must be recorded by the laboratory.

Post-transfusion purpura

A significant fall in platelet count can occur 5-12 days after blood product transfusion. This reaction is caused by previous alloimmunisation to a platelet antigen by transfusion or pregnancy. Treatment is supportive, but if the patient has life-threatening bleeding, then IVIG should be administered.

Non-haemolytic immune reactions

Febrile non-haemolytic transfusion reaction

This is a common occurrence, particularly in the cohort of hospital inpatients. There is an isolated fever >38°C, but less than <2°C from baseline. This can occur up to 2 hours after transfusion completion. Management is temporarily stopping or slowing of the transfusion, giving paracetamol and monitoring closely for a more severe transfusion reaction.

Anaphylaxis

Anaphylaxis is more common when transfusing plasma-rich blood components, such as platelets or FFP. Patients present with shock, bronchospasm, stridor, urticaria or angioedema. The UK Resuscitation Council guidelines recommend:

1. Urgent administration of IM adrenaline. The adult dose is 0.5ml of 1:1000 (500mg).
2. Initial resuscitation and involvement of critical care teams.

In the event of recurrent severe allergic reactions, patients may benefit from receiving washed blood components or components in different additive solutions. Patients with IgA deficiency may be at increased risk of severe allergic reactions due to circulating anti-IgA antibodies.

For mild allergic reactions characterised by rash or itch only, an antihistamine can be administered, and the transfusion restarted at a slower rate.

Transfusion Related Acute Lung Injury (TRALI)

TRALI is caused by passenger donor anti-HLA antibodies.  These react with the recipient’s HLA antigens, in particular in the lungs, causing pulmonary inflammation, leakage of plasma into the alveolar spaces and non-cardiogenic pulmonary oedema. It presents within 2-6 hours of transfusion and is more common with plasma-rich products. It is a diagnosis of exclusion. Symptoms include:

• Severe breathlessness
• Frothy pink sputum
• Hypotension
• Fevers
• Transient neutropenia or monocytopenia.

A chest x-ray may show bilateral perihilar and nodular shadowing.

 Chest X-ray of a patient with TRALI.
Image Source: Wikimedia Commons (2008). Transfusion-related acute lung injury chest X-ray, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Transfusion-related_acute_lung_injury_chest_X-ray.gif (Accessed on: 10 January 2023).

Treatment is supportive, with high concentration oxygen therapy ± ventilatory support. Steroid therapy is not effective. It can be retrospectively confirmed through special investigation to demonstrative antibodies in the donor’s plasma that react with the recipient’s HLA or human neutrophil antigens (HNA). It is important to differentiate from TACO (see non-immune transfusion reactions), as diuretic therapy is not indicated. The incidence of TRALI has reduced since FFP donations have been sourced from male-only donors, as women of child-bearing age may have formed antibodies against non-self red cell antigens during pregnancies.

Transfusion-associated graft-versus-host disease (TA-GvHD)

This rare and fatal complication occurs when viable lymphocytes in a blood donation engraft in the recipient and mount an immune response against the recipient’s cells. At risk patients have impaired cell-mediated immunity and are unable to reject the foreign lymphocytes. These include patients with inherited immunodeficiencies, Hodgkin’s lymphoma, stem cell transplant recipients or those treated with fludarabine, other purine analogues or alemtuzumab. Symptoms occur 7-14 days after transfusion and include fever, rash, diarrhoea, deranged liver function and cytopenias. A biopsy of affected organs will demonstrate GvHD. Patients at risk of developing TA-GvHD must receive irradiated blood components, which damages DNA and inactivates any residual lymphocytes in the blood product following standard leucodepletion.

Non-immune transfusion reactions

Transfusion Associated Circulatory Overload (TACO)

TACO is defined as acute or worsening pulmonary oedema within 6 hours of transfusion and presents with respiratory distress, tachycardia, and clinical evidence of a positive fluid balance. Patients with heart failure, renal impairment, low albumin and fluid overload should have appropriate volume and flow rate prescribed to reduce the risk of TACO. Treatment includes stopping the transfusion, oxygen and diuretic therapy. TACO remains the leading cause of transfusion-related combined mortality and major morbidity. In stable-non-bleeding anaemic patients, medical management of anaemia must be first considered.

Transfusion transmitted infection

Bacterial contamination of blood products is extremely rare. It is more likely to occur with platelet components, stored at 22-24°C degrees, compared to red cells, which are kept refrigerated at 2-6°C and for this reason all platelet donations undergo bacterial culture prior to use. Typical signs include rigors, fever, hypotension and rapid onset shock. The blood component pack may appear normal but should be visibly inspected for clumps and discolouration. Blood cultures should be taken, and intravenous broad-spectrum antibiotics delivered to cover both gram-negative and gram-positive bacteria. The blood component should be sealed and returned to the transfusion laboratory for further investigation so that any associated component can be withdrawn.

Rigorous pre-donation assessment and testing of donated products minimises the risk of transmission of viral infections. All blood donations are screened for hepatitis B, hepatitis C, hepatitis E, HIV and HTLV I and II.

Some blood products are tested for cytomegalovirus (CMV) as CMV-negative blood components are indicated in pregnant women and neonates. In immunocompromised individuals, standard components can be administered as leucodepletion alone is sufficient to reduce the risk of CMV infection. All blood components, apart from granulocytes, are leuco-depleted.