Relationship of Paroxysmal Nocturnal Hemoglobinuria (PNH) Granulocyte Clone Size to Disease Burden and Risk of Major Vascular Events in Untreated Patients: Results from the International PNH Registry

Paroxysmal nocturnal hemoglobinuria (PNH) is caused by acquired gene mutations resulting in deficiency of glycosylphosphatidylinositol (GPI)–anchored complement regulatory proteins on the surface of blood cells, leading to terminal complement–mediated intravascular hemolysis and increased risk of major adverse vascular events (MAVEs). Using data from the International PNH Registry, this study investigated the relationship between the proportion of GPI-deficient granulocytes at PNH onset and (1) the risk for MAVEs (including thrombotic events [TEs]) and (2) the following parameters at last follow-up: high disease activity (HDA); lactate dehydrogenase (LDH) ratio; fatigue; abdominal pain; and rates of overall MAVEs and TEs. A total of 2813 patients untreated at enrollment were included and stratified by clone size at PNH disease onset (baseline). At last follow-up, higher proportion of GPI-deficient granulocytes (≤ 5