A Case Report of a Patient with Paroxysmal Nocturnal Hemoglobinuria Treated with Pegcetacoplan Who Underwent Major Surgery
Authors: Vara Míriam , Moreno Maite , Arzuaga Javier , Hormaza Sara , García-Ruiz Juan Carlos 
Published: December 2023

Paroxysmal Nocturnal Hemoglobinuria (PNH) is characterized by intravascular hemolysis, thrombosis and bone marrow failure. The appearance of the anti-C5 monoclonal antibody eculizumab revolutionized the treatment of PNH, controlling hemolysis and the incidence of thrombosis. However, some patients persist with anemia, due in part to extravascular C3-mediated hemolysis. More recently, the anti-C3 monoclonal antibody pegcetacoplan, which blocks the most proximal part of the complement cascade, has been marketed in Europe, achieving improvements in anemia in these patients. However, intercurrent infectious episodes or surgical interventions can trigger a hemolytic flare, so dose adjustments are necessary to prevent their occurrence. There is hardly any published information or established consensus on how to treat these patients. We present this case as an example of a successful treatment of a patient diagnosed with PNH under treatment with pegcetacoplan who has undergone major surgery.

A 67 year-old man was diagnosed with aplastic anemia in 1997 and treated with immunosuppression (cyclosporine and oxytosone). In 2000, he presented his first intravascular hemolytic crisis with HPN clone detection. He presented several intravascular hemolytic crises for which he was treated with erythropoiesis-stimulating agents, corticosteroids and transfusions.

In 2010, due to deterioration of renal function because of acute hemolysis episode, he started treatment with eculizumab. A reduction in the number of hemolytic crises was observed. However, he required an increase in the dose and frequency of administration of eculizumab due to pharmacokinetic breakthrough hemolysis. After one month of treatment, a positive direct coombs test appeared and presented anemia due to extravascular hemolysis, for which he again required treatment with corticosteroids on specific occasions. For this reason, in December 2022, he started treatment with pegcetacoplan at the usual dose of 1080 mg twice a week subcutaneously (sc). Prior to the start of pegcetacoplan, the patient had hemoglobin levels of 10.3 g/dL, hyperbilirubinemia of 3.2 mg/dL (indirect 2.6 mg/dL), consumed haptoglobin, elevated lactate dehydrogenase (LDH) of 281 U/L and reticulocytosis of 5-6%. Subsequently, since the beginning of pegcetacoplan, he presented clinical improvement, stable hemoglobin (12-13 g/dL) and normalization of reticulocytes, LDH and bilirubin levels. The haptoglobin has remained low until the present time.

In June 2023, the patient underwent major surgery consisting of radical prostatectomy due to a benign prostatic hypertrophy. Suspecting that it might provoke a hemolytic crisis due to surgical stress, the dose of pegcetacoplan was increased as recommended by clinical experts to a dose of 1080 mg every 72 hours sc from one week prior to surgery until one week after. The procedure was carried out without incident and without an increase in hemolysis parameters.

This is the first case report of a patient with PNH treated with pegcetacoplan undergoing major surgery in Spain. In this patient, the perioperative dose increase was successful in preventing the development of a hemolytic crisis.