Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of hematopoietic stem cells. A somatic mutation in the PIGA gene prevents formation of glycosylphosphatidylinositol (GPI) anchors. Without those anchors, affected blood cells cannot display the complement regulators CD55 and CD59. CD55 and CD59 normally restrain complement on the cell surface. In PNH, those protective brakes are missing, so complement can destroy red cells within the circulation. The result is intravascular hemolysis, with release of free hemoglobin into plasma and urine. The name can mislead. Hemolysis is not confined to nighttime; dark urine is often most noticeable on waking because urine has concentrated overnight. The characteristic pattern is a combination of: - Hemolysis: fatigue, pallor, dyspnea, tachycardia, elevated LDH, low haptoglobin, and hemoglobinuria - Thrombosis: often in unusual locations such as the hepatic, portal, cerebral venous, or mesenteric circulation - Bone-marrow dysfunction: anemia with neutropenia and/or thrombocytopenia, particularly when PNH overlaps with aplastic anemia or another marrow disorder Free hemoglobin also scavenges nitric oxide. That can produce abdominal pain, dysphagia or oesophageal spasm, erectile dysfunction, and pulmonary hypertension. The same disease can...