[Current Perspectives on Paroxysmal Nocturnal Hemoglobinuria (PNH)]

Area of Science:

• Hematology
• Immunology
• Pharmacology

Background:

• Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, non-malignant clonal stem cell disorder.
• Characterized by hemolysis, thrombosis, and severe systemic complications, PNH historically has a poor prognosis without treatment.
• Advances in complement inhibition have revolutionized PNH management.

Purpose of the Study:

• To review the pathophysiology, clinical presentation, diagnosis, and treatment of PNH.
• To highlight the benefits of complement-inhibiting therapies in PNH.
• To discuss emerging treatments and their impact on patient outcomes.

Main Methods:

• A comprehensive literature review was conducted.
• Searched databases including PUBMED/NCBI for studies from March 2010 to May 2024.
• 29 selected articles provided in-depth analysis of PNH pathophysiology, diagnosis, and therapeutics.

Main Results:

• Flow cytometry is the gold standard for PNH diagnosis.
• C5 inhibitors (eculizumab, ravulizumab) achieve >95% 5-year survival, reducing hemolysis and thrombosis.
• Emerging proximal complement inhibitors (e.g., iptacopan) show promise in addressing residual extravascular hemolysis and improving hemoglobin levels.

Conclusions:

• Complement inhibitors have shifted PNH from fatal to manageable.
• Optimizing treatment access and infection prophylaxis is crucial.
• Novel therapies offer expanded options, improving patient quality of life and clinical outcomes.