27th May 2023

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.