Treatment outcomes of complement protein C5 inhibition in 509 UK patients with paroxysmal nocturnal hemoglobinuria.

ABSTRACT: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder that occurs on a background of bone marrow failure (BMF). In PNH, chronic intravascular hemolysis causes an increase in morbidity and mortality, mainly because of thromboses. Over the last 20 years, treatment of PNH has focused on the complement protein C5 to prevent intravascular hemolysis using the monoclonal antibody eculizumab and more recently ravulizumab. In the United Kingdom, all patients are under review at 1 of 2 reference centers. We report on all 509 UK patients with PNH treated with eculizumab and/or ravulizumab between May 2002 and July 2022. The survival of patients with eculizumab and ravulizumab was significantly lower than that of age- and sex-matched controls (P = .001). Only 4 patients died of thromboses. The survival of patients with PNH (n = 389), when those requiring treatment for BMF (clonal evolution to myelodysplastic syndrome or acute leukemia or had progressive unresponsive aplastic anemia) were excluded, was not significantly different from that of age- and sex-matched controls (P = .12). There were 11 cases of meningococcal sepsis (0.35 events per 100 patient-years). Extravascular hemolysis was evident in patients who received treatment, with 26.7% of patients requiring transfusions in the most recent 12 months on therapy. Eculizumab and ravulizumab are safe and effective therapies that reduce mortality and morbidity in PNH, but further work is needed to reduce mortality in those with concomitant BMF.

A Rare Case of Severe Hemolytic Anemia and Pulmonary Embolism Secondary to Mycoplasma pneumoniae Infection.

A 27-year-old woman was admitted with a history of dry cough, breathlessness, fever, lethargy, and nausea and vomiting. On examination, she was febrile, jaundiced, and hypoxic. Blood tests revealed severe leucocytosis and severe hemolytic anemia. The chest imaging demonstrated coexisting pneumonia and pulmonary embolism. An initial blood transfusion worsened the hemolytic anemia to the point that critical care review was required. Subsequent blood tests revealed cold agglutinin hemolytic anemia due to Mycoplasma pneumoniae infection. The patient's condition improved after receiving a warm-blood transfusion, antibiotics, and steroid therapy. The patient also received anticoagulant therapy for 6 months. Our case is unique in that the patient had very severe anemia and very severe leucocytosis, making us suspect a hematologic malignancy at initial presentation. This case emphasizes the importance of prompt evaluation of hemolytic anemia and the use of warm blood transfusion for cold agglutinin disease.