# Transfusion-Related Acute Lung Injury

> TRALI pathology for MBBS Pathology: two-hit pathogenesis with donor anti-HLA antibodies, six-hour rule, TACO difference and Indian blood bank practice.

- Canonical URL: https://prepelephant.com/topics/mbbs/pathology/trali-pathology
- Exam / course: MBBS · Subject: Pathology
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-02
- Last updated: 2026-10-02
- How to cite: "Transfusion-Related Acute Lung Injury", PrepElephant, https://prepelephant.com/topics/mbbs/pathology/trali-pathology

## Direct answer

Bilateral lung infiltrates, hypoxia and fever beginning within six hours of transfusion, in a patient without circulatory overload, is transfusion-related acute lung injury (TRALI) — non-cardiogenic pulmonary oedema produced when donor antibodies (class II human leucocyte antigen or human neutrophil antigen specificities, classically from multiparous female donors) meet recipient leucocytes already primed on the pulmonary endothelium. Complement activation, neutrophil aggregation and endothelial breach flood the alveoli with protein-rich fluid; the transfusion is stopped, oxygen and ventilatory support given, and — decisively different from overload — diuretics withheld. TRALI has ranked among the leading causes of transfusion-related mortality, which is why Indian blood banks now follow the mitigation of preferring male or low-risk plasma donors.

## What you must remember

- **Definition criteria:** acute onset within six hours of transfusion; hypoxia; bilateral infiltrates on chest imaging; no evidence of left atrial hypertension (or pulmonary artery pressure normal if measured); no other cause; and either improvement within 48 hours or post-transfusion oxygenation returning to baseline — the standard consensus criteria.
- **Two-hit model:** first hit primes recipient pulmonary endothelium and neutrophils (sepsis, surgery, massive transfusion, malignancy); second hit is the transfused antibody or biologically active lipids, activating neutrophils inside the pulmonary capillaries with capillary leak.
- **Antibody sources:** donor anti-HLA class I and II and anti-HNA antibodies, most often from multiparous or previously transfused donors; a smaller "antibody-negative" fraction is attributed to recipient antibodies or lipids in stored components.
- **TRALI versus TACO:** TRALI is non-cardiogenic — fever, low or normal venous pressure, no response to diuretics, transient leucopenia sometimes; TACO is volume overload — hypertension, raised jugular venous pressure, diuretic-responsive, brain natriuretic peptide elevated; the distinction changes management completely.
- **Management:** stop the transfusion immediately, support oxygenation (up to mechanical ventilation with lung-protective settings), notify the blood bank; avoid diuretics unless overload coexists; most cases resolve within 48-96 hours.
- **Blood bank response:** the implicated donor (especially a female with antibodies) is deferred or restricted from high-plasma components; mitigation strategies — male-predominant plasma, HLA-antibody screening of female donors — have cut TRALI incidence substantially where implemented.
- **Indian context:** with India's National Blood Transfusion Council standards, suspecting and reporting TRALI is a haemovigilance duty; under-recognition remains common because the reaction masquerades as worsening of the underlying illness in a sick patient.
- **Mortality:** reported case fatality in the range of 5-10% in modern series, historically higher.

## A case that turns on one question

A post-operative patient receiving a second unit of packed cells develops fever, tachypnoea and hypoxia 90 minutes into the unit; saturation falls to 84% and chest imaging shows new bilateral infiltrates. The single decisive question: is this volume overload or capillary leak? The jugular venous pressure is not raised, there is no hypertension, and the patient had tolerated the first unit — favouring TRALI, in a surgical (primed) patient receiving plasma-containing components. The response follows the answer: stop the unit, send the remainder and a post-reaction sample to the blood bank for HLA and neutrophil antibody testing against donor and recipient, support the airway with oxygen, and withhold furosemide — giving diuretics to a TRALI patient with a dry right atrium worsens the hypovolaemia without touching the oedema. Had this been instead an elderly renal-impaired recipient with rising jugular venous pressure and furosemide-responsive breathlessness, the label would be transfusion-associated circulatory overload, treated with diuresis. One bedside physiology question — where is the fluid coming from — separates the two.

## Where students slip

The classic error is treating every post-transfusion dyspnoea as fluid overload and reaching for the diuretic loop: in TRALI that both fails and harms. The second slip is timing — students allow 24 hours for the diagnosis; the definition demands onset within six hours, and later events need another explanation. Third, the mechanism question is often answered backwards: it is the donor's antibodies attacking the recipient, not the recipient's attacking the transfused cells — which is precisely why mitigation targets donors (male-predominant plasma pools) rather than recipients, and why the multiparous female donor is the classic source in exam vignettes.

## Frequently asked questions

### Within how long of transfusion must TRALI begin?

Within six hours of transfusion or termination of the implicated unit, per consensus criteria — later dyspnoea points to circulatory overload or other causes.

### What is the two-hit pathogenesis of TRALI?

A first hit (surgery, sepsis, massive transfusion) primes recipient pulmonary neutrophils and endothelium; the second hit — donor anti-HLA or anti-neutrophil antibodies in the component — activates them, causing capillary leak.

### How is TRALI distinguished from transfusion-associated circulatory overload?

TRALI shows fever, normo- or hypotension, normal venous pressures and no benefit from diuretics, whereas TACO shows hypertension, raised venous pressure and diuretic responsiveness.

### Which donors are classically implicated in TRALI?

Multiparous women and previously transfused donors, whose plasma contains anti-HLA class I/II or anti-neutrophil antibodies — hence male-predominant plasma strategies.

### What is the immediate management of suspected TRALI?

Stop the transfusion, support oxygenation (escalating to lung-protective ventilation if needed), notify the blood bank for antibody work-up, and avoid diuretics unless overload coexists.