Transfusion-related acute lung injury (TRALI) following intravenous immunoglobulin infusion in a rituximab immunosuppressed patient with long-shedding SARS-CoV-2.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a rare life-threatening complication of blood product transfusion. Intravenous immunoglobulin (IVIG)-related TRALI is scarcely reported. CASE PRESENTATION: A 63-year-old male patient suffering from multiple sclerosis treated with half-yearly rituximab infusions, was hospitalized due to dry cough, daily fever and shivering for seven days despite antibiotic therapy. Because of the history of COVID-19 one month prior without the symptoms having improved since, persistent bilateral multifocal areas of ground glass opacities in chest computed tomography and positive SARS-CoV-2 PCR from bronchoalveolar lavage with a cycling time of 30.1 COVID-19 due to long-shedding SARS-CoV-2 under immunosuppression with rituximab was diagnosed. He received treatment with nirmatrelvir und ritonavir and because of diagnosed IgG deficiency additionally a single dose of 20 g IVIG. During the IVIG infusion, the patient acutely developed tachycardia, hypotension, fever, chills, and hypoxemic respiratory failure due to pulmonary edema. TRALI was promptly diagnosed, and the patient was transferred to the intensive care unit for non-invasive ventilation for less than 24 h. The patient was discharged home from regular ward 72 h later in a good general condition and no remaining symptoms of TRALI. CONCLUSION: IVIG-related TRALI is a rare but life-threating condition and prompt recognition is lifesaving. Due to an increased use of IVIG not only in long-shedding SARS-CoV-2, an increase of TRALI incidence is expected.

PLATELET SUPPRESSION BY TIROFIBAN AMELIORATES PULMONARY COAGULATION AND FIBRINOLYSIS ABNORMALITIES IN THE LUNGS OF MOUSE ANTIBODY-MEDIATED TRANSFUSION-RELATED ACUTE LUNG INJURY.

ABSTRACT: This study aimed to explore the ameliorating effects of the platelet surface glycoprotein IIb/IIIa receptor antagonist tirofiban on coagulation and fibrinolytic abnormalities in a mouse model of antibody-mediated transfusion-associated acute lung injury (ALI). This is important because ALI is a major cause of death attributable to the occurrence of adverse transfusion reactions. No information on a definite diagnosis or pathological mechanism exists, and targeted treatment options are not available. In this study, wild-type male Balb/c mice aged 8 to 10 weeks were randomly divided into the TRALI model, blank control, tirofiban intervention, and isotype control groups. After different treatment exposures, the mice were observed for 2 h before being killed, and lung tissue samples were collected. To explore the intervention effect of tirofiban, the degree of lung injury was quantified by estimating the lung wet/dry ratio, rectal temperature, survival rate, total protein, and myeloperoxidase and via hematoxylin-eosin staining. Furthermore, the coagulation, anticoagulation, and fibrinolysis assays were measured by automatic coagulation instrument and enzyme-linked immunosorbent assay kits, and the fluorescence densities of platelets and fibrin were quantified using immunofluorescence to analyze the effects of tirofiban on the platelet and fibrin interactions of TRALI. Compared with the TRALI model group, the lung injury indices in the tirofiban intervention group decreased significantly, and survival rates also improved. Furthermore, the level of coagulation and fibrinolytic abnormalities were obviously lower than those in the TRALI model group. In conclusion, our findings suggest that tirofiban might interfere with TRALI by inhibiting platelet activation and improving coagulation and fibrinolytic abnormalities.

rIL-35 prevents murine transfusion-related acute lung injury by inhibiting the activation of endothelial cells.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is an important cause of death associated with transfusion, and no specific clinical treatments are available. Endothelial cells are believed to play an important role in the development of TRALI. This study investigated whether IL-35, an endothelial stabilizing cytokine could regulate the severity of antibody-mediated TRALI in vivo. STUDY DESIGN AND METHODS: Human microvascular endothelial cells (HMVECs) were cultured in vitro, rIL-35(2 µg/mL) was added before HMVECs activation, and HMVECs were fully activated by LPS (0.5 µg/mL). Then cells were collected for flow cytometry analysis. We used a previously established "two-event" mouse model of TRALI with naive and lipopolysaccharide (LPS)-injected mice as controls. rIL-35(100 µg/kg) was injected into the tail vein for 3 consecutive days before the induction of the TRALI model. Samples were collected 2 hours after TRALI induction and tested for lung tissue myeloperoxidase activity, total protein levels, lung tissue histology, endothelial cell activation assay, and cytokine assay. RESULTS: In vitro culture of HMVECs with rIL-35 verified that rIL-35 inhibited endothelial cells. In a mouse model, prophylactic administration of rIL-35 prevented pulmonary edema, increased lung protein levels, and reduced polymorphonuclear neutrophil accumulation in the lung. CONCLUSIONS: This work suggests that antibody-mediated murine TRALI can be prevented by rIL-35, and that rIL-35 appears to work by inhibiting the activation of lung endothelial cells.