What's paroxysmal nocturnal hemoglobinuria?
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired blood disorder in which a faulty group of blood cells lets the body's complement system destroy red blood cells from inside the bloodstream, causing anemia, a risk of dangerous blood clots, and dark urine.
| Also indexed as | ORPHA:447, MONDO:0100244 |
|---|---|
| Features mapped | 12 |
| Treatments mapped | 4 |
| Published sources | 13 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Hemoglobinuria
In paroxysmal nocturnal hemoglobinuria, red blood cells are destroyed inside the blood vessels by the complement system, and the released hemoglobin passes into the urine. This can make the urine dark, and it is classically most noticeable in the morning.
Headache
Headache can occur in paroxysmal nocturnal hemoglobinuria, sometimes related to anemia or to the way the disease affects blood vessels.
Episodic abdominal pain
In paroxysmal nocturnal hemoglobinuria, the destruction of red blood cells can trigger smooth muscle dystonia, spasm of the involuntary muscles that line organs such as the gut, which may be felt as abdominal pain.
Dyspnea
The ongoing destruction of red blood cells in paroxysmal nocturnal hemoglobinuria can cause shortness of breath.
Anemia
Anemia, a shortage of healthy red blood cells, is a common feature of PNH and can cause fatigue and shortness of breath.
Pancytopenia
Many people with PNH have low blood counts across red cells, white cells, and platelets (cytopenias), reflecting the underlying bone marrow problem.
Venous thrombosis
Paroxysmal nocturnal hemoglobinuria carries a strong tendency to form blood clots in the veins. Before complement-blocking treatment, this thrombosis was described as one of the most severe acquired clotting states.
Hemolytic anemia
Paroxysmal nocturnal hemoglobinuria can present as a hemolytic anemia, meaning a low red blood cell count caused by red blood cells being broken apart. The same disorder can also present as bone marrow failure or as a tendency to form blood clots, or as any combination of these.
Thromboembolism
People with PNH have a high risk of thromboembolism (blood clots that block vessels), which is a leading cause of serious illness and death in the disease.
Deep venous thrombosis
Blood clots (thrombosis) are a defining and dangerous feature of paroxysmal nocturnal hemoglobinuria, often forming in unusual sites such as the deep or abdominal veins.
Asthenia
The ongoing destruction of red blood cells in paroxysmal nocturnal hemoglobinuria can cause fatigue, a deep and persistent tiredness.
Intravascular hemolysis
Intravascular hemolysis, the breakdown of red blood cells inside the blood vessels, is the main feature of paroxysmal nocturnal hemoglobinuria. It happens because the affected blood cells lack two surface proteins, CD55 and CD59, that normally protect them from the complement system.
How it is diagnosed
Paroxysmal nocturnal hemoglobinuria
Diagnosed using: Flow cytometry for GPI-anchored proteins (CD55/CD59).
“GPI-anchored complement regulatory proteins CD55 and…”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
Ravulizumab
Ravulizumab is a long-acting medicine given by infusion that blocks the complement protein C5, reducing the destruction of red blood cells in PNH.
Used to help with: Paroxysmal nocturnal hemoglobinuria.
“Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria…”
Eculizumab
Eculizumab is an antibody medicine that blocks the complement protein C5, reducing the complement-driven destruction of red blood cells in PNH.
Used to help with: Paroxysmal nocturnal hemoglobinuria.
“Eculizumab, a first-in-class monoclonal antibody that inhibits terminal complement, is the treatment of choice for patients with severe manifestations of PNH.”
pegcetacoplan
Pegcetacoplan is a proximal complement inhibitor that targets C3. It is used in paroxysmal nocturnal hemoglobinuria, including for people whose response to terminal (C5) complement inhibitors becomes unsatisfactory, and in real-world use it produced rapid improvements in hemoglobin and markers of red-cell destruction.
Used to help with: Paroxysmal nocturnal hemoglobinuria.
“The proximal (C3) complement inhibitor Pegcetacoplan (PEG) improves this situation in clinical…”
iptacopan
Iptacopan is the first oral proximal complement inhibitor that targets factor B. It is used in paroxysmal nocturnal hemoglobinuria and has shown efficacy and safety, including in people who still have anemia from red-cell destruction outside the blood vessels while on a C5 inhibitor.
Used to help with: Paroxysmal nocturnal hemoglobinuria.
“Iptacopan, the first oral proximal complement inhibitor targeting factor B, has shown efficacy and safety in PNH patients.”
What changes how it shows up
Carrying the genetic change is not the whole story. The factors below are described in the research mapped here as changing whether, or how strongly, the condition appears. They modulate how the genotype is expressed; they do not, on their own, cause or cure it.
somatic PIGA mutation (GPI-anchor deficiency, loss of CD55 and CD59)
Paroxysmal nocturnal hemoglobinuria arises when blood-forming stem cells acquire a somatic (non-inherited) mutation in the PIGA gene and expand into a clone. The resulting blood cells lack the GPI-anchored complement-regulating proteins CD55 and CD59, which leaves them unprotected from the complement system and accounts for the destruction of red blood cells inside the blood vessels.
Described as modulating: Paroxysmal nocturnal hemoglobinuria.
“…arises as a consequence of clonal expansion of hematopoietic stem cells that have acquired a somatic mutation in the PIGA gene. The resulting hematopoietic cells have deficiencies in the GPI-anchored complement regulatory proteins CD55 and CD59, which account for the intravascular hemolysis that is the primary clinical manifestation of…”
How to read the evidence labels
Where this comes from
This guide is built from 13 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.