Transfusion-related acute lung injury (TRALI) following intravenous immunoglobulin infusion in a patient with myasthenia gravis Free

Introduction

Transfusion-related acute lung injury (TRALI) is a rare but life-threatening complication of blood product administration, recognized as a leading cause of transfusion-related mortality. It is characterized by acute hypoxemia and non-cardiogenic pulmonary edema within 6 hours of transfusion, without evidence of left atrial hypertension or pre-existing acute lung injury (ALI). The consensus redefinition by Vlaar et al. classifies TRALI as a clinical syndrome with bilateral pulmonary infiltrates, hypoxemia, and no alternative ALI risk factors, explicitly including intravenous immunoglobulin (IVIG) as a potential trigger. IVIG, a pooled human plasma derivative, is widely used for immune-mediated neurologic and hematologic disorders. While IVIG-related complications such as hypersensitivity reactions and volume overload are well-documented, TRALI is rare and likely underdiagnosed.

Case Report

An 82-year-old male presented in myasthenic crisis, with no history of recent transfusions, lung disease, or ALI risk factors. 30 minutes after initiation of IVIG (1 g/kg/day), he developed acute respiratory distress, fever, hypotension, hypoxemia, agitation and hallucinations. The infusion was immediately discontinued. Chest X-ray revealed bilateral interstitial infiltrates. Clinical examination noted tachycardia, respiratory distress, and no signs of jugular venous distension or S3 gallop, further supporting a non-cardiogenic etiology of pulmonary edema. Worsening hypoxemia warranted emergent intubation. Bedside ultrasound showed, inferior vena cava was not dilated, indicating no volume overload, and normal left ventricular function, ruling out left atrial hypertension.

The diagnosis of TRALI was based on the consensus criteria by Vlaar et al.: acute onset within 30 minutes of IVIG infusion, hypoxemia, bilateral infiltrates, no evidence of left atrial hypertension, no pre-existing ALI, and no alternative ALI risk factors. Differential diagnoses, including transfusion-associated circulatory overload (TACO), anaphylaxis, and sepsis, were excluded based on the absence of volume overload, lack of urticaria or angioedema, and negative cultures. Plasmapheresis was initiated for myasthenic crisis, after the second session, he was successfully extubated, with complete resolution of respiratory symptoms.

Discussion

This case illustrates a rare but severe complication of IVIG therapy—TRALI—in a patient with myasthenia gravis (MG). TRALI likely results from a two-hit mechanism: patient factors (unclear in this case) prime pulmonary neutrophils (first hit), and donor-derived factors in IVIG, such as anti-HLA or anti-HNA antibodies, activate these neutrophils, causing endothelial damage and capillary leak (second hit). Non-antibody mediators, such as bioactive lipids or microparticles, may also contribute The high IVIG dose may have increased the concentration of such mediators, heightening TRALI risk.

Clinicians should suspect TRALI in patients developing acute respiratory distress within 6 hours of IVIG infusion, bilateral infiltrates on imaging and no evidence of volume overload. The presence of fever, hypotension, and agitation aligns with findings from Muller et al. The rarity of IVIG-related TRALI (17 cases reported over three decades) may lead to underdiagnosis, as symptoms can mimic anaphylaxis, sepsis, or TACO.

Immediate cessation of IVIG and supportive care, like mechanical ventilation, were critical interventions, consistent with recommendations. Plasmapheresis, initiated for MG, may have incidentally removed circulating antibodies, though its direct role in TRALI resolution is unclear.

Muller et al. reported a 24% mortality rate in IVIG-related TRALI. Strategies to prevent TRALI include screening IVIG donors for antibodies or using male-only plasma. However, the pooled nature of IVIG products complicates the implementation of such measures. Thus, careful patient selection, slow infusion rates, and vigilant monitoring during high-dose IVIG administration are prudent.

The lack of antibody testing limits mechanistic insights. Improved pharmacovigilance is needed to estimate incidence and risk factors, clinicians should report suspected cases to hemovigilance systems to inform safer IVIG manufacturing practices. As IVIG use expands, clinicians must recognize this rare complication, leverage accessible diagnostic tools, and implement prompt supportive care to optimize outcomes.