Febrile Non-Hemolytic and Allergic/Anaphylactic Transfusion Reactions

Febrile non-hemolytic and allergic reactions are the most common adverse effects of transfusion. Febrile reactions present as fever and chills without hemolysis, attributed to recipient antileukocyte antibodies and to cytokines accumulated during component storage. Allergic reactions range from mild urticaria, driven by hypersensitivity to plasma proteins, to rare anaphylaxis, classically described in IgA-deficient recipients with anti-IgA antibodies.

Definition

Febrile non-hemolytic transfusion reactions are transfusion-associated fever and chills not due to hemolysis or infection, while allergic transfusion reactions are hypersensitivity responses to plasma constituents that span mild urticaria to anaphylaxis.

Scope

This entry covers the mechanisms, typical presentations, and laboratory and component-related contributors to febrile and allergic/anaphylactic transfusion reactions, and distinguishes them from hemolytic and pulmonary complications. It is a reference description of these entities, not diagnostic or treatment guidance.

Key concepts

• Febrile non-hemolytic transfusion reaction (FNHTR)
• Antileukocyte (anti-HLA) antibodies
• Storage-derived cytokines
• Leukoreduction
• Urticarial and allergic reactions
• Hypersensitivity to plasma proteins
• IgA deficiency and anti-IgA
• Anaphylactic transfusion reaction

Mechanisms

Febrile non-hemolytic reactions are attributed to two overlapping mechanisms: recipient antibodies (often anti-HLA) reacting with antigens on donor leukocytes, and biologically active cytokines that accumulate in cellular components, particularly platelets, during storage; pre-storage leukoreduction reduces their frequency. Allergic reactions reflect hypersensitivity to soluble plasma proteins in the transfused component, producing histamine-mediated urticaria and, in severe cases, systemic anaphylaxis. A classic, though rare, mechanism of anaphylaxis is the presence of anti-IgA antibodies in an IgA-deficient recipient reacting with donor IgA, as reviewed by Sandler and colleagues. Heddle describes the pathophysiology of febrile reactions and the contribution of leukocytes and cytokines.

Clinical relevance

Distinguishing these common, generally benign reactions from early hemolytic or septic reactions is a core concept in transfusion practice and in interpreting reaction reports. This entry provides reference description of mechanisms and presentations; it does not give premedication, dosing, or individualized management advice.

Epidemiology

Febrile and allergic reactions together account for the large majority of reported transfusion reactions, though they are usually self-limited; their reported frequency has fallen with the adoption of leukoreduction. Anaphylactic reactions are uncommon, and severe anti-IgA-mediated anaphylaxis is rare. Delaney and colleagues summarize the relative frequency of these acute reactions.

History

Febrile reactions were among the first transfusion complications recognized once infectious and hemolytic causes could be excluded, and their link to donor leukocytes motivated the development of leukocyte-reduction methods. The recognition that IgA-deficient recipients could form anti-IgA and suffer anaphylaxis emerged from immunochemical study of plasma proteins in the latter half of the twentieth century.

Seminal works

• heddle-1999
• sandler-1995

Frequently asked questions

What causes a febrile non-hemolytic transfusion reaction?

It is attributed to recipient antibodies reacting with donor leukocytes and to cytokines that accumulate in cellular components during storage; leukoreduction of components reduces how often these reactions occur.

Why can transfusion cause anaphylaxis in some IgA-deficient patients?

A small number of IgA-deficient recipients form anti-IgA antibodies; when transfused components containing donor IgA are given, the antibody can trigger a severe systemic anaphylactic reaction, a rare but well-described mechanism.