From the Guidelines
Paroxysmal Nocturnal Hemoglobinuria (PNH) Definition
PNH is a rare, acquired, life-threatening disease of the blood characterized by the destruction of red blood cells, activation of the coagulation system, and impaired bone marrow function 1.
Key Characteristics
- Destruction of Red Blood Cells: PNH is marked by the clonal expansion of red blood cells that lack the ability to inhibit complement-mediated hemolysis 1.
- Complement Activation: Complement activation plays a major role in the pathogenic effects of PNH, leading to the destruction of red blood cells 1.
- Association with Venous Thrombosis: PNH has been associated with a high propensity for venous thrombosis, particularly in the splanchnic vasculature 1.
Treatment Options
- Eculizumab: A terminal complement inhibitor, administered intravenously at a dose of 600mg weekly for 4 weeks, followed by 900mg at week 5, and then 900mg every 14 days thereafter 1.
- Ravulizumab: Another complement inhibitor, at a dose of 3000mg intravenously as an initial dose, followed by 3000mg every 8 weeks, as an alternative to eculizumab.
Important Considerations
- PNH is an important acquired risk factor for splanchnic vein thrombosis (SPVT) 1.
- Testing for PNH may be considered in cases of suspected SPVT 1.
From the FDA Drug Label
1.1 Paroxysmal Nocturnal Hemoglobinuria (PNH) SOLIRIS is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. The FDA drug label does not provide a definition of Paroxysmal Nocturnal Hemoglobinuria (PNH), it only mentions the indication of the drug for the treatment of PNH.
- Key points:
From the Research
Definition and Characteristics of Paroxysmal Nocturnal Hemoglobinuria (PNH)
- PNH is a rare, chronic hematologic disorder associated with inappropriate terminal complement activity on blood cells, resulting in intravascular hemolysis (IVH), thromboembolic events (TEs), and organ damage 4.
- It is a life-threatening, acquired disease in which blood cells lacking complement regulatory proteins are destroyed due to uncontrolled complement activity 5.
- PNH is characterized by the destruction of hematopoietic cells through activation of the complement system, with manifestations that can be life-threatening, including hemolysis, thrombosis, and marrow failure 6.
Pathophysiology and Clinical Complications
- The disease is caused by an acquired mutation in the phosphatidylinositol glycan (PIG)-A gene, leading to a deficiency of glycosylphosphatidylinositol (GPI)-anchors and GPI-anchored proteins on the surface of affected blood cells 7.
- PNH red blood cells are highly vulnerable to activation of complement and the formation of the membrane attack complex (MAC), resulting in chronic intravascular hemolysis 7.
- Clinical complications of PNH include anemia, fatigue, transfusion requirements, renal impairment, pulmonary hypertension, and risk of severe thromboembolic events 4, 7.
Relationship with Other Diseases
- There is a strong link between PNH and other acquired bone marrow failure syndromes, including myelodysplastic syndrome (MDS) 8.
- Cytogenetic, morphological abnormalities or both are observed in the range of MDS/PNH diagnosis, and distinction between these entities may be difficult in some cases 8.
Treatment and Management
- The main objective of PNH treatment is prevention of morbidity and mortality due to terminal complement activation, with the aim of improving patient outcomes 4.
- Terminal complement inhibitors, such as eculizumab and ravulizumab, have shown efficacy in controlling terminal complement-mediated IVH, reducing TEs and organ damage, and improving health-related quality of life in patients with PNH 4, 5.
- Allogeneic hematopoietic cell transplantation (HCT) remains the sole cure for PNH, but eculizumab has been used to prevent complement-mediated hemolysis in patients with PNH since its approval by the Food and Drug Administration in 2007 6.