When TACO Runs Hot: Rethinking Fever in Transfusion-Associated Circulatory Overload

caitlinraymondmdphd
Nov 4
3 min read

For years, transfusion-associated circulatory overload (TACO) has been framed as a purely hemodynamic problem — a case of too much blood, too fast. But hemovigilance data are challenging that simplicity. A growing body of work suggests that in a significant subset of patients, TACO runs hot.

Yes, fever. Not chills from contamination, not cytokine-release fever from a leukocyte-rich product, but true fever within hours of transfusion — sometimes the only obvious clue that something is wrong. And it’s not rare: recent studies suggest that 30–40 % of TACO cases involve fever, a rate higher than for allergic transfusion reactions with fever. [1- 3]

Beyond Volume: A Hotter Kind of Overload

Classically, TACO is defined by acute respiratory distress and hydrostatic pulmonary edema within six to twelve hours after transfusion. But the presence of fever doesn’t fit that simple model of mechanical overload.

Research by Parmar et al. (2017) and others shows that these fevers aren’t linked to patient age, product age, or reaction severity — and in most cases they’re new-onset, not continuations of pre-existing fever. [1] Together with bedside biovigilance data showing inflammatory features in some TACO cases, [2 - 4] this has led to a re-imagining of the syndrome: TACO may be part hemodynamic, part inflammatory.

The Two-Hit Hypothesis: Volume Meets Inflammation

The two-hit hypothesis of “inflammatory TACO” frames the reaction as a meeting of two vulnerabilities:

First hit: a susceptible patient — one with heart failure, renal disease, positive fluid balance, or critical illness that limits their ability to tolerate volume.
Second hit: the transfusion itself, delivering not only volume but also biologically active mediators — cytokines, storage-lesion byproducts, and shifts in colloid osmotic pressure.

This combination may tip the endothelium into dysfunction, increasing capillary permeability and producing pulmonary edema beyond what simple volume overload would explain. It also helps account for “hot-TACO” cases after even a single unit of blood. [2 - 4]

Clinical Confusion: When “Hot-TACO” Mimics TRALI

Fever blurs the lines. In a febrile, hypoxic patient post-transfusion, most clinicians first suspect TRALI or sepsis. Yet as multiple studies and the revised international case definition emphasize, [1, 3, 5] the presence of fever doesn’t exclude TACO.

If there are clear hydrostatic findings — positive fluid balance, elevated BNP or NT-proBNP, echocardiographic evidence of elevated filling pressures, or improvement with diuretics — TACO should remain high on the list even when fever is present.

Diagnostic Pearls: Sorting the Hot from the Heavy

When TACO and TRALI overlap, these clues help steer the differential:

🕒 Timing: TACO usually develops within 6 hours, but may be delayed up to 12. TRALI is classically within 6 hours and not relieved by diuretics.
💧 Volume response: Improvement with diuretics or fluid restriction supports TACO.
❤️ BNP / NT-proBNP: Ratios > 1.5–2× pre-transfusion favor hydrostatic overload.
🫁 Chest imaging: TACO shows cardiomegaly and vascular redistribution; TRALI typically presents with bilateral non-cardiogenic infiltrates.
🧪 Inflammatory markers: Fever alone doesn’t rule out TACO, but a marked cytokine surge (e.g., IL-8, IL-6) suggests TRALI or sepsis.

Ultimately, distinguishing hot-TACO from other febrile transfusion reactions depends on pattern recognition rather than a single test. The key is to remember that not all TACO is “cold.” Sometimes, the circuit overload burns a little.

References