~20,000 people have PNH worldwide.1
PNH can affect any age group, but is often diagnosed in people ~30-40 years old.2,3
As PNH is ultra-rare, it can be difficult to detect. Fewer than 40% of people with PNH receive a diagnosis within 12 months of symptom onset and 24% of all PNH diagnoses can take five years or longer.4
Symptoms of PNH vary greatly from one person to another and not everyone has every symptom.2 Symptoms are also common to many diseases, and appear gradually, making a diagnosis of PNH easily overlooked.
Paroxysmal:
sudden and irregular
Nocturnal:
at night
Haemoglobinuria:
presence of haemoglobin in urine
The name refers to passing dark urine in the morning, which is a common symptom of PNH, however not all people with PNH experience this symptom.3 Haematologists will often use signs of intravascular haemolysis (destruction of red blood cells in the circulation with the release of cell contents into the plasma), thrombosis (blood clots which blocks veins or arteries) and cytopenia (reduced number of blood cells) as clinical indications of PNH.4
In the bone marrow, stem cells act as templates for blood cells. In a healthy person, specific proteins are present on the surface of red blood cells to protect them.
In a person with PNH, some stem cells have a mutated gene, called the phosphatidylinositol glycan class A gene (PIG-A), which causes red blood cells to be produced without certain proteins (CD55 and CD59) which protect them from the body’s immune system.
The complement system, a part of the immune system, mistakes these red blood cells as invaders, and kicks off a chain of events to destroy them.2, 5
In PNH, the destruction of red blood cells (haemolysis) can lead to many symptoms which can dramatically affect the quality of life.
If PNH is not appropriately treated, it can lead to life-threatening health problems, such as3:
PNH is currently treated with C5 complement inhibitors, which target the C5 protein in the complement system and stop the destruction of red blood cells.6 The treatment of PNH has improved with the advent of complement inhibitors, however, current treatment is associated with:
Frequent, life-long treatment, given subcutaneously or intravenously. Regular intravenous administration can be a significant treatment burden and impact daily life.2,3
Inadequate disease control as the effects of the disease, such as anaemia and the need for transfusions, may persist due to incomplete C5 inhibition.6,7,8,9,12
Genetic resistance to C5 inhibitors in a small percentage of people with PNH, which prohibits them from benefiting from current treatments.10
Many people with PNH worldwide lack treatment options and access.11
It is essential to further research the intricacies of the complement system, to investigate and provide better treatment options, including to those who cannot access it, to transform the lives of people with PNH.
References
Grand View Research. Paroxysmal nocturnal hemoglobinuria (PNH) treatment market size, share and trends analysis report by treatment and segment forecasts, 2018 – 2025. [Internet; cited August 2022]. Available from:
Peri C. Paroxysmal nocturnal hemoglobinuria (PNH). [Internet; cited August 2022]. Available from:
National Organization for Rare Diseases. Paroxysmal nocturnal hemoglobinuria. [Internet; cited August 2022]. Available from:
Parker C. et al. 2005. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. doi: 10.1182/blood-2005-04-1717
Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124:2804-2811.
Harder M, et al. Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation. Blood. 2017;129:970-980.
Risitano AM, et al. Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: Time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019;10:1157.
Röth A, et al. The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria. Blood. 2020;135(12):912–920.
Brodsky RA. How I treat paroxysmal nocturnal hemoglobinuria. Blood. 2009;113(26):6522–6527.
Nishimura J, et al. Genetic variants in C5 and poor response to eculizumab. N Engl J Med. 2014;370:632-639.
Cançado RD et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematol Transfus Cell Ther. 2021;43(3):341-348.
De Latour RP et al. Assessing complement blockade in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab. Blood. 2015;125:775-783.
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