Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria

Abstract

SummaryParoxysmal nocturnal haemoglobinuria (PNH) has been recognised as a discrete disease entity since 1882. Approximately a half of patients will eventually die as a result of having PNH. Many of the symptoms of PNH, including recurrent abdominal pain, dysphagia, severe lethargy and erectile dysfunction, result from intravascular haemolysis with absorption of nitric oxide by free haemoglobin from the plasma. These symptoms, as well as the occurrence of thrombosis and aplasia, significantly affect patients' quality of life; thrombosis is the leading cause of premature mortality. The syndrome of haemolytic-anaemiaassociated pulmonary hypertension has been further identified in PNH patients. There is currently an air of excitement surrounding therapies for PNH as recent therapeutic developments, particularly the use of the complement inhibitor eculizumab, promise to radically alter the symptomatology and natural history of haemolytic PNH.

A Prospective Multicenter Study of Paroxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure

“…Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation leading to intravascular hemolysis and an inflammatory prothrombotic state (1,2). The etiology of this rare hematopoietic stem cell disorder is an acquired clonal genetic deficiency of glycosylphosphatidylinositol (GPI)-anchored and GPIlinked proteins on the surface of blood cells.…”

Detection of PNH cells by flow cytometry, using multiparameter analysis

“…The involved different mutations result in the deficient synthesis of glycosylphosphatidylinositol (GPI)-anchor molecule and the resulting partial or absolute deficiency, in all blood cell lineages, of the expression of GPI-anchored membrane proteins, like CD55, CD59, CD14, CD16, CD24, CD48, among others (1,7,15,18) .…”

The prothrombotic state in paroxysmal nocturnal hemoglobinuria: a multifaceted source

“…19 PNH red blood cells can be labeled type I, II or III; type I cells have normal expression of GPI-APs, type II have partial deficiency and type III lack all GPI-APs. 20 The clinical manifestations are variable; intravascular hemolysis, thrombosis and anemia are significant, however, other symptoms may be present. 1 Schrezenmeier et al analyzed 1610 patients and showed the proportion of symptoms, such as fatigue (80%), dyspnea (64%), hemoglobinuria (62%), abdominal pain (44%), chest pain (33%) and impaired renal function (14%), with only 16% of patients having a history of thrombotic events.…”