Transfusion-Related Acute Lung Injury (TRALI) is acute respiratory distress within six hours of transfusion, characterized by fever, hypoxia, hypotension, and bilateral infiltrates without circulatory overload. The main pathophysiological mechanism is immune-mediated, involving donor anti-HLA antibodies activating recipient neutrophils, triggering cytokine release, endothelial injury, and capillary leakage. These antibodies often arise from alloantigen exposure, especially in multiparous women. We report two HIV-positive patients on mechanical ventilation for opportunistic infections, who developed TRALI after transfusion of one Packed Red Blood Cell (PRBC) unit from female donors considered low-risk.

Case 1: A 55-year-old woman, newly diagnosed with HIV and antiretroviral treatment-naive, was admitted with CMV meningitis and suspected pneumocystosis with possible TB coinfection. She developed acute kidney injury, likely from sulfamethoxazole-trimethoprim or iodinated contrast, and ventilator-associated pneumonia. After clinical improvement, she received one PRBC unit during hemodialysis for Hb 6.2 g/dL and Hct 17.9%. One hour post-transfusion, she developed acute respiratory distress, crackles, and desaturation despite optimized ventilation, diuretics, and steroids. Echocardiogram excluded pulmonary embolism and volume overload. She progressed to severe hypotension, bradycardia, and cardiopulmonary arrest. The blood center investigation revealed a nulliparous female donor with repeated donations. HLA testing showed donor anti-HLA Class I antibody A30:01 and recipient allele A30:EUCZR, indicating strong immunogenetic compatibility. Case 2: A 20-year-old man, newly diagnosed with HIV and antiretroviral treatment-naive, on mechanical ventilation for pneumocystosis and TB, experienced ventilatory worsening after bronchoaspiration, requiring vasopressors and antimicrobials. With Hb 6.8 g/dL and Hct 20.1%, he received one PRBC unit. One hour after transfusion began, he developed sudden respiratory deterioration, requiring ventilation adjustments and prone positioning. Chest X-Ray showed novel bilateral infiltrates; echocardiogram ruled out volume overload, and fluid balance was negative. He died from multifactorial causes. The donor was a phenotyped woman with one prior pregnancy and previous donations.

TRALI is rare but potentially fatal, with mortality of 5%–10%, especially in critically ill or ventilated patients. Early recognition and donor screening are essential. Brazilian guidelines classify both donors as low-risk (nulliparous or ≤2 pregnancies) and thus not restricted from donation. In Case 1, HLA compatibility supports immune-mediated TRALI; in Case 2, clinical features suggest TRALI despite no detected antibodies. Major patient-related risk factors include age, female sex, smoking, alcohol use, positive fluid balance, pre-transfusion shock, sepsis, malignancies, cardiac disease, and mechanical ventilation.[1] HIV is not a proven independent risk factor, but comorbidities in PLHA may predispose to TRALI. Conclusion: These cases demonstrate TRALI can arise from donors traditionally considered low-risk, highlighting the need to explore non-immunological mechanisms, including red blood cell factors. In critically ill PLHA, high clinical suspicion for TRALI is warranted.