PNH

Paroxysmal nocturnal hemoglobinuria is caused by an acquired somatic mutation in the PIGA gene of a hematopoietic stem cell. This mutation impairs synthesis of GPI anchors, so red blood cells lack protective GPI‑anchored proteins, especially CD55 and CD59. Without these regulators, complement-mediated intravascular hemolysis occurs, leading to hemoglobinuria and other complications.

Treatment for paroxysmal nocturnal hemoglobinuria (PNH) centers on complement inhibition (eculizumab or ravulizumab) to reduce hemolysis, supportive care with red-cell transfusions, folate and iron management, and anticoagulation when thrombosis risk or occurrence is present. Allogeneic stem-cell transplantation is the only curative option. Vaccination and prophylactic antibiotics are required before complement-inhibitor therapy.

Life expectancy in paroxysmal nocturnal hemoglobinuria (PNH) varies. Historically median survival was about 10–15 years due to thrombosis and bone marrow failure, but modern complement inhibitor therapy (eculizumab, ravulizumab) has markedly improved outcomes. Many treated patients now have near-normal life expectancy, though risks (thrombosis, infections, organ damage) persist and require lifelong management; transplant can be curative in select cases.

Paroxysmal nocturnal hemoglobinuria causes chronic hemolytic anemia with fatigue, pallor, jaundice and dark red urine (hemoglobinuria), often noticed in the morning. Patients commonly have abdominal pain, dysphagia, erectile dysfunction and shortness of breath. They’re at high risk for recurrent, potentially life‑threatening thromboses (hepatic, portal, cerebral), renal impairment, chest pain and bone marrow failure with increased infection risk.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, potentially life‑threatening blood disorder causing complement‑mediated red‑cell destruction, chronic hemolysis, anemia and high risk of thrombosis — the leading cause of death. It can cause renal failure, pulmonary embolism, stroke, and bone marrow failure. Severity varies widely; outcomes have improved with complement inhibitors and stem cell transplant, but close monitoring and treatment are essential.

PNH is suspected from symptoms (hemoglobinuria, fatigue, thrombosis) and hemolysis labs: low hemoglobin, elevated LDH and bilirubin, low haptoglobin, reticulocytosis, and a negative direct antiglobulin (Coombs) test. Diagnosis is confirmed by flow cytometry showing absent or reduced GPI-anchored proteins (CD55/CD59 or FLAER binding) on blood cells; bone marrow exam and PIGA genetic testing may be used.