From the Guidelines
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a hematologic disorder characterized by clonal expansion of red blood cells that lack the ability to inhibit complement-mediated hemolysis. This condition is marked by the deficiency of GPI-anchored proteins, including complement regulatory proteins CD55 and CD59, which normally protect red blood cells from complement-mediated destruction 1. The key characteristics of PNH include:
- Complement-mediated hemolysis
- Thrombosis
- Bone marrow failure Eculizumab, a C5 inhibitor, is approved for use in PNH and works by blocking serum hemolytic activity 1. PNH occurs due to an acquired mutation in the PIGA gene in hematopoietic stem cells, leading to the deficiency of GPI-anchored proteins, including CD55 and CD59 1. The clinical manifestations of PNH can vary, but they often include:
- Nocturnal hemoglobinuria
- Fatigue
- Shortness of breath
- Thrombosis
- Bone marrow failure It is essential to note that PNH is a rare acquired blood disorder, and its diagnosis requires a comprehensive evaluation, including flow cytometry and molecular testing 1.
From the FDA Drug Label
- 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 treatment of the condition with the drug. Paroxysmal Nocturnal Hemoglobinuria (PNH) is not defined in the provided drug labels 2, 2, or 3.
From the Research
Definition and Characteristics of Paroxysmal Nocturnal Hemoglobinuria (PNH)
- PNH is a rare, acquired clonal hematopoietic cell disease characterized by the destruction of hematopoietic cells through activation of the complement system 4.
- It manifests with hemolytic anemia, bone marrow failure, and thrombosis, which can be life-threatening 4, 5.
- PNH arises from a somatic mutation of the PIG-A gene in a hematopoietic stem cell, leading to a deficiency of surface proteins that protect cells against complement-mediated attack 5.
Clinical Features and Treatment
- Clinical features of PNH include intravascular hemolysis, hemoglobinuria, and thrombosis 4, 5.
- Eculizumab, a humanized antibody that inhibits the activation of terminal complement components, has been shown to reduce intravascular hemolysis, hemoglobinuria, and the need for transfusion in patients with PNH 5, 6, 7.
- Treatment with eculizumab can improve anemia, decrease intravascular hemolysis, and reduce the risk of thrombosis 6, 7.
- 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 4.
Response to Treatment
- Responses to eculizumab therapy can vary, and may depend on underlying marrow failure, inflammatory conditions, and red cell clone size following treatment 6.
- Complete response to eculizumab is defined as transfusion independence with normal hemoglobin for age/sex, absence of symptoms, and lactate dehydrogenase <1.5 times the upper limit of normal 6.
- Long-term treatment with eculizumab has been shown to sustain efficacy and improve survival in patients with PNH 7.