From the Research
Definition and Characteristics of Paroxysmal Nocturnal Hemoglobinuria (PNH)
- PNH is a rare, acquired chronic hemolytic anemia, often associated with recurrent nocturnal exacerbations, recurrent infections, neutropenia, thrombocytopenia, and episodes of venous thrombosis 1.
- It is characterized by a triad of hemolytic anemia, pancytopenia, and thrombosis, making it a unique clinical syndrome 1.
- PNH is caused by somatic mutations in the PIGA gene, leading to a deficiency of glycosylphosphatidylinositol (GPI) anchors and a lack of complement inhibitors, such as CD55 and CD59, on the surface of blood cells 2, 3.
Clinical Manifestations and Complications
- Clinical manifestations of PNH include intravascular hemolytic anemia, increased thrombotic risk, and end-organ damage, such as fatigue, chest pain, dyspnea, renal failure, and pulmonary hypertension 4.
- The loss of CD55 and CD59 renders PNH erythrocytes susceptible to intravascular hemolysis, which can lead to thrombosis and morbidity and mortality 2.
- The accumulation of anaphylatoxins from complement activation may also play a role in the clinical manifestations of PNH 2.
Treatment and Management
- Therapeutic strategies for PNH include terminal complement blockade and bone marrow transplantation 2.
- Eculizumab, a monoclonal antibody complement inhibitor, is highly effective and the only licensed therapy for PNH 2, 3.
- New complement inhibitors, such as ravulizumab and pegcetacoplan, have been approved, and biosimilars of eculizumab are also available 4.
- Novel therapeutics, including proximal inhibitors, are in late-stage clinical trials, and a centralized international registry is being developed to capture and analyze data on PNH management 4.