When the Textbook Walks Through the Door: IgA Deficiency and Transfusion Practice

A patient was admitted with a congestive heart failure exacerbation. Their hemoglobin was drifting downward — nothing dramatic, but enough to warrant a type and screen. The result wasn’t surprising: a known warm autoantibody. What was surprising was the note that popped up beside it — “Requires washed RBCs.”

We looked into it. The patient’s IgA level was reported as < 5 mg/dL on two separate occasions — a true, complete selective IgA deficiency. No history of anaphylactic reactions, no documentation of transfusion reactions at all. Still, the washed requirement persisted, a permanent flag carried forward through admissions like a family heirloom no one quite questioned.

The Spectrum of IgA Deficiency

Selective IgA deficiency is the most common primary immunodeficiency, occurring in roughly 1 in 300 people, though the term encompasses a spectrum. Many individuals have low but detectable levels of IgA and remain entirely asymptomatic.

A complete deficiency — defined by an undetectable IgA level on at least two separate occasions — is far less common. (This definition is used by the European Society for Immunodeficiencies and the Immune Deficiency Foundation.) Only a fraction of these individuals go on to form anti-IgA antibodies, which have been implicated in allergic or anaphylactic transfusion reactions.

The Rare Meets the Real

The classic teaching looms large in every pathology and transfusion board prep book: the IgA-deficient patient who develops life-threatening anaphylaxis after receiving a standard blood component.

But outside the exam room, this scenario is exceedingly rare.The true incidence of anti-IgA–mediated anaphylaxis is unknown and appears extremely low. The literature contains only a handful of case reports and small series describing such reactions, mostly in patients with severe IgA deficiency and detectable anti-IgA antibodies [1–4].

A comprehensive review identified just 23 cases of anaphylaxis in immunodeficient patients receiving IVIG over several decades [2]. Even among those with measurable anti-IgA, many tolerate blood products and immunoglobulin infusions without incident [1].

The association between anti-IgA antibodies and anaphylaxis remains controversial — suggesting that other, still-uncharacterized modulators of immune reactivity may determine who reacts and who does not. Larger studies are needed to clarify the true risk and mechanisms [1].

In short: the event is exceptional in clinical practice.

And for our particular patient — elderly, volume-sensitive, admitted for heart failure — the most likely transfusion complication would not be anaphylaxis at all, but TACO. The same physiology that brought them into the hospital also raises their risk for fluid overload if transfused.

Re-examining the “Requires Washed RBCs” Reflex

So where does that leave us? With vigilance, yes — but also with perspective. The patient’s risk for anaphylaxis appears theoretical, not demonstrated. Yet the “washed RBCs” flag carries real-world costs: longer wait times, product scarcity, and potential delays in care.

We decided to order an anti-IgA assay to see whether we could safely lift the restriction — a small act of course-correction that might spare the patient unnecessary complexity in future transfusions.

Because sometimes the best transfusion practice isn’t about adding more caveats.

It’s about knowing which ones no longer serve the patient.

References

1. Rachid R, Bonilla FA. The Journal of Allergy and Clinical Immunology. 2012;129(3):628-34.

2. Williams SJ, Gupta S. Archivum Immunologiae et Therapiae Experimentalis. 2017;65(1):11-19.

3. Salama A et al. Transfusion. 2004;44(4):509-11.

4. Ahrens N et al. Clinical and Experimental Immunology. 2008;151(3):455-8.