Transfusion Related Acute Lung Injury: Symptoms, Types, Causes and Treatment

Transfusion Related Acute Lung Injury (TRALI) is a severe and potentially life-threatening reaction that can occur after receiving blood transfusions. Although once considered rare, TRALI is now recognized as one of the leading causes of transfusion-related mortality. Understanding the symptoms, types, causes, and treatment of TRALI is crucial for both healthcare professionals and patients who may receive transfusions. This article provides a comprehensive, evidence-based overview of TRALI, synthesized from leading research sources.

Symptoms of Transfusion Related Acute Lung Injury

TRALI presents with a striking and acute clinical picture, often within hours of transfusion. Recognizing these symptoms early is critical for effective management and patient safety. The onset is typically sudden, and the symptoms can be severe and frightening for both patients and caregivers.

Symptom	Description	Onset	Source(s)
Dyspnea	Sudden shortness of breath	<6 hours	1 2 5 8 13
Hypoxemia	Low blood oxygen levels	Rapid	2 5 8 13
Pulmonary Edema	Non-cardiogenic fluid in lungs	Rapid	2 4 5 8 13
Fever	Moderate elevation in temperature	Often present	1 5 13
Hypotension	Low blood pressure, may be unresponsive to fluids	Often present	1 2 5 13
Chills	Sensation of cold with shivering	Sometimes	1

Table 1: Key Symptoms

Recognizing TRALI in Clinical Practice

The hallmark of TRALI is the abrupt onset of respiratory distress, usually within 1–6 hours after a transfusion. Patients often experience the following:

• Severe shortness of breath (dyspnea): This is typically the first symptom and may progress rapidly.
• Hypoxemia: Oxygen saturation drops quickly, sometimes to dangerously low levels, requiring immediate intervention 2 5 8 13.
• Non-cardiogenic pulmonary edema: Unlike heart failure, the lung edema in TRALI is not caused by fluid overload or cardiac dysfunction. Chest X-rays reveal bilateral infiltrates, but the heart size remains normal 5 8 13.
• Fever and chills: A moderate fever is common, often accompanied by chills 1 5 13.
• Hypotension: Blood pressure frequently drops and may not respond to standard fluid resuscitation 1 2 5 13.

Distinguishing TRALI from Other Lung Injuries

TRALI is often misdiagnosed as other forms of acute lung injury (ALI) or adult respiratory distress syndrome (ARDS). Key distinctions include:

• Temporal relationship to transfusion: Symptoms appear within 6 hours of transfusion 2 5 8 13.
• Exclusion of cardiac causes: Pulmonary edema in TRALI is non-cardiogenic, with normal or low pulmonary wedge pressures 5.
• Rapid improvement: With supportive care, most patients show significant improvement within 48–96 hours, unlike ARDS from other causes, which can linger or worsen 5 13.

Types of Transfusion Related Acute Lung Injury

TRALI is not a "one-size-fits-all" syndrome. Its clinical expression and underlying mechanisms can vary. Understanding the types of TRALI helps clinicians tailor their prevention and management strategies.

Type	Mechanism	Key Features	Source(s)
Antibody-Mediated	Donor antibodies attack recipient leukocytes	Rapid onset, often severe	2 3 4 6 8 12 13
Non-Antibody-Mediated	Biologically active lipids or other mediators	Associated with older blood products	3 4 8 12 13 14

Table 2: Types of TRALI

Antibody-Mediated TRALI

The classic form of TRALI results from the passive transfer of donor antibodies:

• How it occurs: Donor plasma contains anti-HLA or antigranulocyte antibodies. When transfused into a recipient with matching leukocyte antigens, these antibodies bind and activate neutrophils in the lungs, causing capillary leaks and edema 2 3 4 6 8 12 13.
• Who is at risk: Recipients of plasma from multiparous female donors, who have a higher likelihood of antibody formation due to prior pregnancies, are especially at risk 6 9 10 12.
• Clinical presentation: Onset is typically rapid and dramatic.

Non-Antibody-Mediated TRALI

Not all TRALI cases are due to antibodies:

• How it occurs: In some cases, biologically active substances such as lipids accumulate in stored cellular blood products. These substances can prime and activate neutrophils, leading to lung injury even in the absence of antibodies 3 4 8 12 13 14.
• Clinical scenarios: More common with older blood products and in patients with underlying inflammation or critical illness (the so-called "two-hit" model) 3 4 8 12.
• Recognition: These cases may be harder to diagnose but are increasingly acknowledged as a significant subset.

The Two-Hit Model

Modern understanding often frames TRALI as a two-step process:

1. First hit: The patient’s underlying condition primes the pulmonary endothelium and neutrophils (e.g., surgery, infection, inflammation) 3 4 8 12.
2. Second hit: Transfusion delivers antibodies or biological mediators, triggering full-blown lung injury 3 4 8 12.

Both antibody and non-antibody mechanisms may operate simultaneously or in different patients.

Causes of Transfusion Related Acute Lung Injury

Recognizing the causes of TRALI is vital for both prevention and early intervention. A variety of donor, recipient, and blood product factors contribute to TRALI risk.

Cause	Description	Risk Factors	Source(s)
Donor Antibodies	Anti-HLA or antigranulocyte antibodies in plasma	Multiparous women, prior sensitization	2 3 4 6 8 9 10 12
Biologically Active Lipids	Lipids and mediators from stored blood	Older blood, cellular products	3 4 8 12 13 14
Recipient Risk Factors	Patient’s underlying illness or inflammation	Surgery, sepsis, liver disease, alcohol abuse, smoking	3 4 9 10 12
Blood Product Type	Plasma-rich products increase risk	Platelets, FFP, whole blood	2 8 9 10 14

Table 3: Causes and Risk Factors

Donor-Related Causes

• Antibody Presence: Most TRALI cases are linked to the transfusion of blood products containing donor-derived anti-HLA or antigranulocyte antibodies 2 3 4 6 8 9 10 12.
• High-Risk Donors: Multiparous women have a higher likelihood of developing these antibodies due to exposure during pregnancy 6 9 10 12.
• Blood Component Implicated: Plasma-rich products such as fresh frozen plasma, platelets, and whole blood are most frequently involved 2 8 9 10 14.

Blood Product-Related Causes

• Biologically Active Mediators: Stored red blood cells and platelets can accumulate biologically active lipids and other mediators over time. These substances may independently trigger TRALI, especially in susceptible patients 3 4 8 12 13 14.
• Shelf Life and Storage: The risk appears to increase with the age of the blood product, although this is less pronounced compared to antibody-mediated TRALI 14.

Recipient-Related Causes

• Patient Susceptibility: Certain conditions predispose patients to TRALI:
  • Major surgery (especially cardiac and liver procedures) 9
  • Chronic alcohol abuse 9
  • Sepsis or systemic inflammation 3 4 9 12
  • High airway pressures during ventilation 9
  • Positive fluid balance and smoking 9
• The “First Hit”: These underlying conditions prime the lungs and immune system, setting the stage for TRALI when the transfusion is administered 3 4 8 12.

Epidemiological Observations

• Reduced Risk by Changing Donor Policy: Limiting plasma donations from female donors has significantly reduced TRALI incidence 9 10.
• Still Underdiagnosed: Many cases go unrecognized or are misattributed to other causes of acute lung injury, emphasizing the need for education and vigilance 1 2.

Treatment of Transfusion Related Acute Lung Injury

TRALI is a medical emergency requiring prompt, supportive care. While no specific treatment exists, advances in understanding are paving the way for future therapies.

Treatment	Approach	Purpose/Outcome	Source(s)
Supportive Care	Oxygen, ventilation, fluids	Stabilize breathing, correct hypoxemia	5 8 13 14
Mechanical Ventilation	Intubation if necessary	Severe cases, maintain oxygenation	5 13 14
Avoid Diuretics	Unless fluid overload is proven	Edema is non-cardiogenic	5 8 13 14
No Specific Therapy	Research ongoing	Investigational (e.g., IL-10, anti-inflammatory agents)	11 12
Monitor & Report	Notify blood bank, monitor patient	Prevent recurrence, donor tracking	1 2 8 10

Table 4: Treatment Strategies

Supportive Management

• Immediate cessation of transfusion: If TRALI is suspected, stop the transfusion at once 8 13 14.
• Oxygen therapy: Most patients require supplemental oxygen, and many need high-flow oxygen or non-invasive ventilation 5 8 13 14.
• Mechanical ventilation: In severe cases, intubation and mechanical ventilation are necessary to maintain adequate oxygenation 5 13 14.
• Fluid management: Avoid aggressive fluid administration. Since the edema is non-cardiogenic, diuretics are not routinely recommended unless there is clear evidence of fluid overload 5 8 13 14.

Investigational and Future Therapies

• No specific pharmacologic treatment: Currently, no drugs are approved specifically for TRALI 5 8 13 14.
• Potential therapies: Research in animal models suggests promising interventions, such as:
  • Interleukin-10 (IL-10) therapy, which may protect against antibody-mediated TRALI 11 12
  • Agents that modulate inflammatory pathways (e.g., C-reactive protein, IL-8 blockers, antioxidants) 12
• Clinical application: These therapies are not yet available for routine clinical use and are in the research phase 11 12.

Prevention and Reporting

• Blood bank notification: Report all suspected TRALI cases to the blood bank for donor investigation and prevention of future incidents 1 2 8 10.
• Donor management: Blood centers increasingly exclude high-risk donors (such as multiparous women) from donating plasma-rich products 9 10.
• Education and awareness: Enhancing clinical recognition is key to timely diagnosis and management 1 2 8 10.

Prognosis

• Generally favorable: With prompt supportive care, most patients recover fully within 48–96 hours 5 8 13 14.
• Mortality risk: Fatalities can occur, especially in patients with multiple comorbidities or delayed recognition 5 13 14.
• Long-term outlook: Survivors typically have an excellent long-term prognosis, with no lasting lung damage 13.

Conclusion

TRALI is a serious, life-threatening complication of transfusion, but outcomes are generally good with early recognition and supportive care. Here’s a recap of the key points:

• Symptoms: Rapid onset of respiratory distress, hypoxemia, pulmonary edema, fever, and hypotension within 6 hours of transfusion 1 2 5 8 13.
• Types: Includes both antibody-mediated and non-antibody-mediated forms, with the “two-hit” model explaining most cases 2 3 4 6 8 12 13 14.
• Causes: Primarily due to donor anti-leukocyte antibodies or biological mediators in stored blood; recipient risk factors and product type also play key roles 2 3 4 6 8 9 10 12 13 14.
• Treatment: Supportive care is mainstay; research into targeted therapies is ongoing. Prevention focuses on careful donor selection and rapid case identification 5 8 9 10 11 12 13 14.

Early recognition and management are crucial. With increased awareness and evidence-based approaches, the risks of TRALI can be minimized, ensuring safer transfusion practices for all patients.