title: Management of paroxysmal nocturnal haemoglobinuria: a personal view.
abstract: Paroxysmal nocturnal haemoglobinuria (PNH) is a serious form of acquired haemolytic anaemia with several features that make it unique, including the fact that it is caused by clonal expansion, in the context of bone marrow failure, of a haematopoietic stem cell that has a somatic mutation in a gene crucial for the synthesis of glycosylphosphatidylinositol anchors; and that this also produces a life-threatening acquired thrombophilic state. Until recently, the two only main options for patients with PNH were either allogeneic bone marrow transplantation or supportive management, including blood transfusion: both options require some skill and good patient-doctor collaboration. Since the start of this millennium a major advance has been the introduction of eculizumab, a monoclonal antibody that targets the C5 protein of the complement system: blockade of C5 prevents activation of the complement distal pathway, and thus abrogates the complement-mediated intravascular haemolysis that severely plagues patients with PNH. This review outlines an approach to the management of all three major components of the clinical picture of PNH--namely haemolysis, thrombosis and bone marrow failure--based on the literature and on personal experience. We consider specifically how the use of eculizumab has modified other aspects of the management of PNH, and even the pathophysiology itself of this disease. Finally, we develop a treatment algorithm which others might find helpful.
authors.affiliation: Istituto Toscano Tumori, Florence, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Luzzatto
authors.forename: Giacomo
authors.initials: G
authors.lastname: Gianfaldoni
authors.forename: Rosario
authors.initials: R
authors.lastname: Notaro
mesh_terms: D000741:Anemia, Aplastic; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants / Q000627:therapeutic use; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D016026:Bone Marrow Transplantation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006457:Hemoglobinuria, Paroxysmal / Q000628:therapy*; D006461:Hemolysis; D006801:Humans; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy; D015912:Thrombolytic Therapy / Q000379:methods; D013927:Thrombosis / Q000188:drug therapy
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; C481642:eculizumab