How should transfusion‑related acute lung injury (TRALI) be recognized, managed, and prevented?

Transfusion-Related Acute Lung Injury (TRALI)

Recognition and Diagnosis

TRALI presents as acute respiratory distress with hypoxemia, dyspnea, and bilateral pulmonary infiltrates developing within 1-6 hours of transfusion, distinguished from circulatory overload by the presence of hypotension rather than hypertension. 1, 2

Key Diagnostic Features

• Timing: Symptoms typically appear 1-2 hours after transfusion, with most cases manifesting within 6 hours 2, 3
• Respiratory: Severe hypoxemia, dyspnea, tachypnea, bilateral pulmonary infiltrates, and fluid in the endotracheal tube if intubated 4, 2
• Cardiovascular: Hypotension (not hypertension), tachycardia, and potential cardiovascular instability 2, 5
• Other signs: Fever, cyanosis, and pulmonary secretions 6

Critical Differential Diagnosis

The presence of hypotension is the key feature that distinguishes TRALI from transfusion-associated circulatory overload (TACO), which presents with hypertension and cardiovascular changes suggesting fluid overload. 4, 2

TRALI must also be differentiated from acute hemolytic reactions, which present with hemoglobinuria, fever, and microvascular bleeding rather than the prominent respiratory distress seen in TRALI 2

Immediate Management

Stop the transfusion immediately at the first sign of suspected TRALI—this is the single most critical intervention that can prevent progression to severe morbidity or mortality. 1, 2

Step-by-Step Management Algorithm

1. Immediate cessation and access: Stop transfusion and maintain IV access with normal saline 1, 2

2. Respiratory support:

   • Administer 100% high-flow oxygen immediately 2
   • Call for help and prepare for potential intubation and mechanical ventilation 2
   • Monitor peak airway pressure in ventilated patients 1

3. Hemodynamic support:

   • Maintain blood pressure (MAP >65-70 mmHg) with IV fluid resuscitation using normal saline or lactated Ringer's solution 2
   • Prepare vasopressors if fluid resuscitation is insufficient 4

4. Critical pitfall to avoid: Do NOT administer diuretics—they are ineffective for TRALI and may worsen the condition. 1, 2, 3 This is a non-cardiogenic pulmonary edema requiring supportive care, not volume removal.

5. Monitoring: Check vital signs every 5-15 minutes including heart rate, blood pressure, temperature, respiratory rate, and oxygen saturation 4

Supportive Care

• Provide critical care supportive measures focusing on respiratory support 1
• Maintain appropriate fluid balance without overhydration 1
• Most patients recover within 96 hours with appropriate supportive care 2
• Glucocorticoid use remains controversial with insufficient evidence to recommend routine administration 3

Reporting and Investigation

Report every suspected case to the local blood bank immediately—TRALI is a leading cause of transfusion-associated mortality and is significantly underdiagnosed and underreported. 1, 2

Mandatory Actions

• Contact the transfusion laboratory without delay to initiate investigation and ensure traceability 4, 2
• This reporting removes the implicated donor from the pool and prevents future occurrences 2
• Send post-reaction blood samples for complete blood count, direct antiglobulin test, repeat crossmatch, PT, aPTT, and fibrinogen to exclude hemolytic reaction 2
• Continue observation for at least 24 hours, as TRALI can evolve over the first 6-12 hours post-transfusion 2

Prevention Strategies

Blood banks have implemented donor screening measures that have dramatically reduced TRALI incidence, including the use of male-only plasma donors and screening for leukocyte antibodies. 1, 4

Evidence-Based Prevention Measures

• Plasma donor selection: Since 2009 in Germany, only plasma from male donors or female donors without pregnancy history (or with negative HLA/HNA antibody testing) is used, resulting in zero TRALI-related deaths since implementation 3
• The UK implemented male-only plasma for component therapy beginning in 2003, which dramatically reduced TRALI incidence 4
• Testing of female apheresis platelet donors for HLA antibodies has been implemented as an additional risk reduction strategy 1

High-Risk Blood Products

Fresh frozen plasma (FFP) and platelet concentrates are the blood products most frequently implicated in TRALI due to their high plasma volume and potential for containing leukocyte antibodies. 1, 4, 3

Clinical Prevention

• Carefully assess the need for transfusion, especially in high-risk patients 1
• Transfuse single units in non-hemorrhaging patients and reassess before giving additional units 4
• The risk of TRALI rises with each additional transfused blood component 4

Pathophysiology

The mechanism involves donor leukocyte antibodies (HLA class I, class II, or granulocyte-specific antibodies) interacting with recipient neutrophils, causing granulocytes in lung capillaries to release oxygen radicals and enzymes that damage endothelial cells and cause pulmonary edema 2, 3, 6

A non-immune mechanism also exists, involving biologically active lipids from stored platelet and red blood cell concentrates that activate neutrophilic granulocytes, typically resulting in a more benign clinical course 3, 7