Paroxysmal nocturnal hemoglobinuria (PNH) is a hemolytic anemia caused by an acquired defect of the (PIGA) gene, which leads to dysfunction of a red cell membrane protein (glycosylphosphatidylinositol) that is normally responsible for protecting RBCs from complement-mediated destruction. PNH can present with (particularly and episodic hemoglobinuria), systemic vasoconstriction, , and pancytopenia. It can also occur in patients with aplastic anemia or myelodysplastic syndrome. Diagnostics typically reveal with a negative direct Coombs test (DAT), and PNH can be confirmed using flow cytometry of peripheral blood. Management ranges from watchful waiting and supportive care to targeted anti-C5 antibody therapy (e.g., eculizumab, ravulozumab) for patients with significant clinical manifestations. Notable complications include Budd-Chiari syndrome, infections, and acute leukemia.
Epidemiological data refers to the US, unless otherwise specified.
- Physiologically, a membrane-bound glycosylphosphatidylinositol (GPI) anchor protects RBCs against complement-mediated hemolysis.
- Acquired mutation on the PIGA gene located on the X chromosome → GPI anchor loses its protective effect → RBC destruction by complement and reticuloendothelial system → intravascular and extravascular hemolysis 
- The GPI anchor proteins involved in PNH are:
- PNH can also occur in patients with aplastic anemia and MDS. 
- Pallor, excessive fatigue, weakness
- Intermittent jaundice
- Episodes of hemoglobinuria causing pink/red/dark urine which usually occurs in the morning due to the concentration of urine overnight. 
- Vasoconstriction 
- Venous thrombosis in unusual locations (e.g., hepatic, cerebral, and/or abdominal veins) 
- Increased risk of infections (in case of pancytopenia)
- CBC: anemia, thrombocytopenia, and/or pancytopenia ; usually ↑ reticulocytes 
- : ↓ haptoglobin, hemosiderinuria, hemoglobinuria 
- Direct Coombs test: negative 
- Flow cytometry of peripheral blood (confirmatory test for PNH): can show deficiency of GPI-linked proteins on the surface of RBCs and WBCs (e.g., CD55, CD59) 
- Bone marrow biopsy: not required for the diagnosis of PNH, but indicated in patients with significant pancytopenia
- Additional studies: to assess for complications, for example:
Typical biochemical findings in hemolysis include ↓ haptoglobin, ↑ LDH concentration, ↑ indirect bilirubin concentration, peripheral blood smear abnormalities (e.g., ↑ reticulocytes, schistocytes, spherocytes, polychromasia), and urinalysis abnormalities (e.g., hemoglobinuria, hemosiderinuria, and urobilinogen).
- Patients with mild or no clinical manifestations: with close surveillance
- Patients with significant clinical manifestations: Start targeted therapy.
- Provide supportive care for all patients.
Targeted therapy 
- Indications include severe anemia, thrombosis, severe fatigue, pain crises, and end-organ damage
- First-line treatment: complement inhibition with an anti-C5 antibody (e.g., eculizumab , ravulozumab)
- Second-line treatment:
Supportive care 
- Consider hemolysis or a history of VTE and have not been treated with eculizumab. for patients who have active
- Avoid medications that increase the risk of thrombosis (e.g., ).
- Start therapeutic anticoagulation without delay for any venous thromboembolic event (e.g., deep vein thrombosis, pulmonary embolism).
- Decisions regarding therapeutic anticoagulation for arterial thromboembolic events should be made in consultation with a specialist.
- Neisseria meningitidis infection
- Vasoconstriction and thrombotic emboli leading to thrombotic complications, e.g., infarction, 
- Development of acute leukemia
- Renal failure
- Smooth muscle dystonia
- Pulmonary hypertension
We list the most important complications. The selection is not exhaustive.