[Current Perspectives on Paroxysmal Nocturnal Hemoglobinuria (PNH)]

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a non-malignant clonal hematopoietic stem cell disorder characterized by intravascular and extravascular hemolysis, thrombosis, and potentially life-threatening systemic complications. Without treatment, the 5-year survival rate is approximately 50%. Advances in complement-inhibiting therapies have significantly improved the quality of life and survival of these patients.

To review the pathophysiology, clinical presentation, diagnosis, and current and emerging treatments for PNH, highlighting the benefits of complement-inhibiting drugs.

A literature review of the literature on the pathophysiology and treatments of PNH was conducted, covering studies from March 2010 to May 2024. The review included 42 articles from PUBMED/NCBI, of which 29 met the inclusion criteria and were selected for an in-depth analysis of pathophysiology, diagnosis, and therapeutic options.

Flow cytometry is the diagnostic method of choice for identifying PNH clones. Patients with classical PNH treated with C5 inhibitors (eculizumab and ravulizumab) exhibit an overall survival rate exceeding 95% at 5 years, with significant reductions in hemolysis, thrombotic episodes, and transfusion dependency. However, persistent extravascular hemolysis remains a challenge affecting morbidity and mortality. New proximal complement pathway inhibitors, such as iptacopan, have demonstrated greater efficacy in controlling extravascular hemolysis and improving hemoglobin levels.

The introduction of complement-inhibiting therapies has transformed classical PNH from a fatal disease into a manageable chronic condition. It is essential to optimize access to these treatments and ensure adequate prophylaxis against encapsulated infections. New drugs expand therapeutic options, further improving clinical outcomes and patients' quality of life.