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

Breakthrough hemolysis (BTH) is the return of hemolytic disease resulting in an overall increase in complement activation in a patient being treated for paroxysmal nocturnal hemoglobinuria (PNH) with complement inhibitors (CI). BTH after COVID-19 vaccination has only been reported in PNH patients treated with the traditional C5 CI eculizumab and ravulizumab. We report on a new association of BTH in a newly COVID-19 vaccinated, previously stable PNH patient treated with pegcetacoplan, a C3 CI. The patient is a 29-year-old female diagnosed with PNH in 2017 and was started on eculizumab but was switched to pegcetacoplan in 2021 after continuing to exhibit symptomatic hemolysis. Subsequently, the patient returned to PNH remission serologically and symptomatically until her first COVID-19 vaccination. Since then, her lactate dehydrogenase (LDH) and hemoglobin counts have not fully returned to previous baseline levels, with significant exacerbations after her second COVID-19 vaccine and de novo COVID-19 infection. As of May 2022, the patient requires packed red blood cell transfusions every two to three months and has undergone a bone marrow transplant evaluation. This case study suggests that the administration of the upstream C3 CI, pegcetacoplan, is associated with active extravascular hemolysis in the setting of COVID-19 vaccinations and active COVID-19 infection. The pathophysiology of this hemolysis is unclear as hemolysis could be related to the underlying complement factor deficiency or amplification of complement factors causing extravascular hemolysis. There are conflicting reports in the literature regarding the mechanism by which COVID-19 vaccination and infection cause BTH in PNH patients, regardless of the choice of CI treatment. Bringing awareness to this case of BTH secondary to COVID-19 in a PNH patient treated with pegcetacoplan can further warrant the investigation of the role of COVID-19 in complement disruption and its role in BTH.