Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-rare, genetically acquired, life-threatening disease of the blood where the body’s complement system destroys its red blood cells.
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:
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.