In Cureus, clinicians presented the case report of an individual with paroxysmal nocturnal hemoglobinuria (PNH) who developed breakthrough hemolysis associated with coronavirus disease 2019 (COVID-19) vaccination and active COVID-19 infection. 

Although COVID-19 vaccination is overwhelmingly safe for the general population, breakthrough bleeding has been documented to occur in a small number of patients with PNH. 

A 29-year-old woman with a previous history of PNH was initially started on eculizumab but was switched to pegcetacoplan due to symptomatic hemolysis. The patient then entered a period of remission until her first Pfizer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. After she received her first vaccine dose, her lactate dehydrogenase (783 U/L) and hemoglobin (7.6 g/dL) levels did not recover to baseline levels. In addition, she experienced fatigue, lethargy, and evidence of active hemolysis. 

After the patient received her second Pfizer SARS-CoV-2 vaccination, she experienced a de novo COVID-19 infection and significant exacerbations, including shortness of breath, exertional chest pain, easy bruising, and gingival bleeding when she brushed her teeth. Her lactate dehydrogenase levels rose to 1056 U/L and her hemoglobin levels were 6.1 g/dL. She required packed red cell transfusions every 2 to 3 months. She also underwent a bone marrow transplant evaluation. 

Read more about PNH etiology

“This case study suggests that the administration of the upstream C3 [complement inhibitor], pegcetacoplan, is associated with active extravascular hemolysis in the setting of COVID-19 vaccinations and active COVID-19 infection,” the authors wrote. 

The patient’s clinicians could not be certain of the cause of her hemolysis, as it could be the result of complement factor deficiency or an exacerbation of complement factors resulting in extravascular hemolysis. 

It should be highlighted that the exact relationship between breakthrough bleeding and COVID-19 vaccination/infection has yet to be elucidated. This case report, as well as others, should prompt further studies into the role of COVID-19 in complement disruption and its possible role in driving breakthrough bleeding. 

“This data provides a basis for additional investigation to clarify the mechanism of interaction between the COVID-19 vaccine, the COVID-19 virus, and current PNH [complement inhibitor] therapies,” the authors of the study concluded.


Boshkos MC, Fives KR, Phrathep DD, Healey KD, Patel M. Breakthrough hemolysis associated with COVID-19 vaccination and active COVID-19 infection in a patient with paroxysmal nocturnal hemoglobinuria maintained on pegcetacoplan: a case report. Cureus. 2023;15(3):e36240. doi:10.7759/cureus.36240