In Focus
Pulmonary transfusion reactions
Insights and management
Hemovigilance standardizes pulmonary transfusion reactions. The potential causes for a suspected pulmonary transfusion reaction include transfusion associated circular overload (TACO), transfusion related acute lung injury (TRALI) and severe allergic reaction.
Definitions for this reaction categories have in common the presence of hypoxia or difficulty breathing1-4. However, transfusion recipients usually have pre-existing medical conditions and coincidental treatments that might also cause breathing difficulties. Therefore, the benefit of hemovigilance systems is the standardization of classification of transfusion reactions, and standardized terminology of describing the likelihood of the transfusion vs. other possible coinciding causes (imputability). This allows for aggregation of transfusion reaction data across institutions, and the ability of healthcare providers to communicate with consistent definitions and concepts.
Differentiating Severe Allergic reaction, TACO, and TRALI
There are key differentiating characteristics of an allergic reaction, TACO, and TRALI. A severe allergic reaction with pulmonary involvement is characterized by additional signs/symptoms of involving another organ system (hypotension, skin rash, hives). A severe allergic reaction with difficulty breathing is usually associated with a constriction of the bronchial airways, excess mucous secretion, and/or swelling of the throat and tongue. In contrast, both TACO and TRALI are associated with the filling of the alveolar spaces with extracellular fluid due to either excess intravascular fluid volume (TACO) or increased permeability of the pulmonary capillaries (TRALI). Differentiating TACO from TRALI in isolation can be achieved by using the various criteria for TACO which include evidence of excess fluid balance, increased blood pressure, other signs of congestive heart failure, and resolution of hypoxia with diuresis. With the exclusion of severe allergic reaction and TACO, the diagnosis of TRALI can be considered and is considered a diagnosis of exclusion—assuming other causes of acute lung injury other than transfusion are excluded.
Assessing for overlapping TACO and TRALI, and pre-existing pulmonary conditions
One challenge of hemovigilance criteria for TRALI is that TACO needs to be excluded in past definitions. However, it is possible for patients to have both TACO and TRALI (or some other form of acute lung injury). An approach to diagnosing both is to treat TACO with diuresis if possible, and if the patient fails to fully recover to baseline, simultaneous TRALI or underlying acute lung injury can be considered. The other challenge of hemovigilance criteria for TRALI is that underlying causes of acute lung injury are to be excluded and like TACO and TRALI, patients can have an underlying acute lung injury and also experience TRALI. Revised definitions to TRALI have been proposed to allow for TRALI to be considered in the context of pre-existing acute lung injury if the patient’s baseline pulmonary status worsens in association with a transfusion reaction, and with the assumption or belief that the underlying non-transfusion related lung injury was stable and not progressing4.
Management: Immediate supportive treatment of patient and discontinuation of transfusion
In all instances of transfusion reactions, the transfusion should be discontinued, and supportive treatment should be initiated until the suspected transfusion reaction is further investigated. Commonly, severe allergic reactions may require both the use of antihistamines and epinephrine. TACO might benefit from the use of diuresis and in patients with end-stage renal disease, may require dialysis to remove the excess intravascular fluid. All three reaction types (allergic, TACO, TRALI) if life-threatening, might also require protection of the airway with intubation and mechanical ventilation, and increased oxygen support.
Avoid giving two products from the same donor during the same hospitalization
The goals of management of a suspected pulmonary transfusion reaction are to limit further harm to the patient and to other potential transfusion recipients. One key principle is to avoid giving the same patient more of the suspected blood product if a separate simultaneous collection or split collection was made for patients suspected of having an allergic or TRALI reaction. This is a distinct possibility with the increasing use of apheresis collections, which allow for multiple units to be manufactured from the same donor. Usually, the paired products will have the same donor identification number (DIN) to allow for ready identification within an institution.
Identify blood donors at higher risk of causing TRALI
Some but not all blood donors are screened for HLA antibodies, nor are donors necessarily screened for HNA antibodies. An investigation into whether a donor has anti-leukocyte antibodies by the blood center may include testing of the patient for the corresponding antigen. Not having corresponding antibody-antigen matches does not exclude TRALI as TRALI can also be caused by accumulated biologic response modifiers in the blood product5. Nonetheless, blood centers who identify a donor with antibodies reactive to high prevalence HLA or HNA antigens through such an investigation may refrain from further collections from such a donor.
Choosing or modifying products in response to past reactions
TACO is not a donor specific reaction so there is no recommended change in the selection of products. However, greater attention to overall fluid balance, slower transfusion rates, the use of diuretics between multiple transfusions, and smaller volumes of transfusions are often considered to avoid TACO recurrence. For severe allergic reactions, the underlying cause is often the plasma proteins in the product. Using products with additive solutions for RBC or platelet units (if not previously used for the patient) can reduce the exposure to the allergen without needing to manually centrifuge the product to remove the remaining plasma or washing the product. Washing of RBC or platelet units might be unavoidable for patients with anaphylactic or anaphylactoid reactions, as premedication with antihistamines and glucocorticosteroids may be insufficient. For urgent transfusions where washing of products or the ability to obtain IgA-deficient plasma for IgA deficient patients are not possible, the use of a combination of antihistamines, glucocorticosteroids, and epinephrine with a slow rate of transfusion might be considered. For TRALI, besides avoiding a split or simultaneous collection from the same donor, the general belief is that there is no increased risk in the selection of random blood components for future transfusions.
References
1. NHSN CDC Hemovigilance Module. https://www.cdc.gov/nhsn/biovigilance/blood-safety/index.html 2. ISBT Haemovigilance Working Party Proposed standard definitions for surveillance of non infectious adverse transfusion reactions
3. Schipperus MR, Wiersum-Osselton JC; ISBT-IHN-AABB TACO Definition Revision Group. Updated definitions for respiratory complications of blood transfusion. Transfusion. 2019;59(7):2482-2483. doi:10.1111/trf.15389
4. Vlaar APJ, Toy P, Fung M, et al. A consensus redefinition of transfusion-related acute lung injury. Transfusion. 2019;59(7):2465-2476. doi:10.1111/trf.15311
5. Kapur R. Key features of the underlying pathophysiology of Transfusion-related acute lung injury. Expert Rev Hematol. 2025;18(1):57-64. doi:10.1080/17474086.2024.2436972
