From the Guidelines
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired haematological disorder of haematopoietic stem cells. This condition is characterized by its strong association with certain vascular diseases of the liver, such as Budd-Chiari syndrome (BCS) 1. The key feature of PNH is the presence of a PNH cell population, which can increase the risk of thrombosis, particularly when this population exceeds 60% of the granulocytes 1.
Key Characteristics of PNH
- It is a rare acquired disorder
- Associated with haematopoietic stem cells
- Strongly associated with BCS
- Reported in 9–19% of tested BCS patients 1
- Increases the risk of thrombosis, especially with a high PNH cell population
Clinical Considerations
Testing for PNH should be routinely performed in all BCS patients and considered in patients with portal vein thrombosis (PVT) 1. The exact mechanism for the development of splanchnic vein thrombosis (SVT) in PNH is yet unknown 1.
Management and Risk Factors
While the provided evidence does not delve into the management of PNH, it highlights the importance of identifying PNH in the context of vascular diseases of the liver. Hormonal factors, including oral contraceptive use and pregnancy, are considered risk factors for SVT, which may be relevant in the broader management of patients with PNH 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 treatment of the condition with the drug. Paroxysmal Nocturnal Hemoglobinuria (PNH) is not defined in the provided drug labels 2, 3, or 4.
From the Research
Definition of Paroxysmal Nocturnal Hemoglobinuria (PNH)
- PNH is an ultra-orphan disease characterized by hemolytic anemia, bone marrow failure, and thrombosis 5, 6, 7, 8, 9
- It arises from PNH stem cells in the bone marrow, which expand and produce red blood cells, white blood cells, and platelets that lack cell surface markers, making them vulnerable to complement-mediated destruction 5, 8
Pathophysiology of PNH
- The lack of cell surface markers, such as CD55 and CD59, on PNH cells leads to uncontrolled complement activation, resulting in intravascular hemolysis and thrombosis 5, 6, 7, 8, 9
- Complement activation, endothelial dysfunction, and impaired bioavailability of nitric oxide contribute to the pathogenesis of thrombotic events in PNH patients 9
Clinical Manifestations of PNH
- Symptoms of PNH include abdominal pain, difficulty swallowing, erectile dysfunction, and red or black urine (haemoglobinuria) 5
- Thrombosis is a major clinical manifestation of PNH, affecting up to 40% of individuals, with venous thrombosis being more prevalent 9
- PNH can also lead to bone marrow aplasia, resulting in anemia, leukopenia, and thrombocytopenia 5, 6, 7, 8, 9
Treatment Options for PNH
- Eculizumab, a monoclonal antibody that inhibits C5 in the terminal complement cascade, has revolutionized the treatment of PNH, improving life expectancy and quality of life for patients 5, 7, 8
- Ravulizumab, a longer-acting C5 inhibitor, has been approved for the treatment of PNH and has shown comparable efficacy to eculizumab 5, 6
- Novel complement inhibitors and anticoagulants, such as warfarin and low-molecular-weight heparin, are being developed and used in combination with C5 inhibitors to manage thrombotic events in PNH patients 9