A recent study published in the International Journal of Molecular Sciences suggests respiratory viral infections may increase the risk of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH) on complement inhibitor treatment

PNH is characterized by hemolytic anemia and thrombosis. These disease manifestations often drive significant morbidity and mortality; thrombosis is the main cause of death in roughly half of the patients with this disorder. Hemolysis, although less fatal, can lead to organ damage, increasing the burden of the disease. Hemolysis can also increase thrombotic risk. 

Preliminary evidence suggests that viral infections can trigger acute hemolysis. Most recently, the SARS-CoV-2 infection has been linked to breakthrough hemolysis. However, no studies have been conducted assessing the potential association between viral infections and hemolysis in PNH. Thus, the authors of this study sought to investigate any links between the two conditions.  

The research team assessed 34 patients with PNH who presented with fever and/or coryzal symptoms; they were then assessed for evidence of respiratory virus infections. Relevant clinical data were collected such as duration of eculizumab treatment, previous thrombotic/hemolytic episodes, and the use of prophylaxis and/or immunosuppressants. 

Read more about PNH etiology 

Researchers tested the recruited patients for 10 respiratory infections and also assessed white cell and neutrophil count and C-reactive protein levels. Disease severity was assessed based on the need for antibiotic/antiviral treatment or hospitalization. To assess impact on breakthrough hemolysis, the research team measured lactate dehydrogenase and bilirubin levels, which when deranged suggest that a hemolytic episode has occurred. 

Among the 34 patients, 11 had a documented respiratory viral infection. The research team observed that these patients had higher inflammatory markers, with the majority requiring antibiotic treatment, and 3 requiring intensive care hospitalized treatment. The research team also reported that these patients demonstrated prominent evidence of breakthrough hemolysis with an associated drop in hemoglobin. 

“Overall, our data indicate that respiratory virus infections may pose a significant risk for breakthrough hemolysis in PNH patients, underlying the need for influenza and SARS-CoV-2 immunization, regular screening, and close monitoring of symptomatic and high-risk PNH patients,” the authors concluded.


Lazana I, Mangion SA, Babiker S, et al. The effect of respiratory viral infections on breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria. Int J Mol Sci. Published online May 27, 2023. doi:10.3390/ijms24119358