Researchers presented a case report on a patient with paroxysmal nocturnal hemoglobinuria (PNH) who achieved transfusion independence and abolition of extravascular hemolysis after being treated with pegcetacoplan. The study was published in Frontiers in Immunology. 

A man aged 79 years was diagnosed with PNH in November 2020. In 2007, he had been diagnosed with calreticulin gene (CALR) mutated essential thrombocythemia and was treated with hydroxyurea. In 2016, he experienced an increase in lactate dehydrogenase (LDH) 1.6 times the upper limit of normal. This was accompanied by mild unconjugated hyperbilirubinemia and progressive anemia. 

From October 2019 onward, he required 1 red blood cell unit of transfusion every 2 months due to overt hemolysis. Direct and indirect antiglobulin tests were negative.

A new bone marrow trephine revealed trilinear hypercellularity and an increase in marrow fibrosis, consistent with a fibrotic evolution of essential thrombocythemia. The patient was treated with steroids followed by danozol for hemolytic anemia, to no avail. 

Read more about PNH etiology 

“Given the presence of steroid-resistant [direct antiglobulin test]-negative hemolytic anemia, in November 2020, [fluorescent aerolysin] analysis was done at our center and demonstrated the presence of a large PNH clone in 43% of [erythrocytes], 90.6% of granulocytes, and 92.3% of monocytes,” the authors of the study wrote. 

The patient was started on intravenous eculizumab 900 mg fortnightly. This caused his LDH levels to normalize, but his hemoglobin levels remained low. He eventually needed blood transfusions of 2 red blood cell units per month. 

In March 2022, the patient was started on pegcetacoplan in addition to his existing eculizumab treatment. His hemoglobin levels improved and he no longer required blood transfusions after the second treatment dose. Eculizumab was discontinued and the patient was administered subcutaneous pegcetacoplan 1080 mg twice weekly. 

“Finally, the PNH clone size on [erythrocytes] increased from 43% to 87% after pegcetacoplan,” the authors of the study wrote. “Serial [direct antiglobulin test] evaluations at 1, 3, and 6 weeks after pegcetacoplan start confirmed negativity of C3 deposition on the patient’s [erythrocytes].” 

Pegcetacoplan works by preventing C3 deposition on erythrocytes and reduces extravascular hemolysis, thus removing one of the major barriers to the optimal performance of anti-C5 monoclonal antibodies such as eculizumab and ravulizumab. 


Fattizzo B, Versino F, Zaninoni A, et al. Case report: transfusion independence and abolition of extravascular hemolysis in a PNH patient treated with pegcetacoplanFront Immunol. 2022;13:1060923. doi:10.3389/fimmu.2022.1060923