Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents

Antonio M Risitano, Bruno RotoliHematology, Department of Biochemistry and Medical Biotechnologies, Federico II University of Naples, ItalyAbstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal non-malignant hematological disease characterized by the expansion of hematopoietic stem cells (H...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Antonio M Risitano, Bruno Rotoli
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2008
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a0269f5c0eeb49e3abdebbb0ea43c018
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a0269f5c0eeb49e3abdebbb0ea43c018
record_format	dspace
spelling	oai:doaj.org-article:a0269f5c0eeb49e3abdebbb0ea43c0182021-12-02T04:45:11ZParoxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents1177-54751177-5491https://doaj.org/article/a0269f5c0eeb49e3abdebbb0ea43c0182008-06-01T00:00:00Zhttp://www.dovepress.com/paroxysmal-nocturnal-hemoglobinuria-pathophysiology-natural-history-an-a1727https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Antonio M Risitano, Bruno RotoliHematology, Department of Biochemistry and Medical Biotechnologies, Federico II University of Naples, ItalyAbstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal non-malignant hematological disease characterized by the expansion of hematopoietic stem cells (HSCs) and progeny mature cells, whose surfaces lack all the proteins linked through the glycosyl-phosphatidyl inositol anchor. This defect arises from an acquired somatic mutation in the X-linked phosphatidyl-inositol glycan class A gene, with subsequent clonal expansion of the mutated HSCs as a result of a concomitant, likely immune-mediated, selective pressure. The disease is characterized by complement-mediated chronic intravascular hemolysis, resulting in hemolytic anemia and hemosiderinuria; capricious exacerbations lead to recurrent gross hemoglobinuria. Additional cardinal manifestations of PNH are a variable degree of bone marrow failure and an intrinsic propensity to thromboembolic events. The disease is markedly invalidating, with chronic symptoms requiring supportive therapy &minus; usually including periodical transfusions; possible life-threatening complications may also ensue. The biology of PNH has been progressively elucidated in the past few years, but therapeutic strategies remained unsatisfactory for decades, the only exception being stem cell transplantation, which is restricted to selected patients and retains significant morbidity and mortality. Recently, a biological agent to treat PNH has been developed &minus; the terminal complement inhibitor eculizumab &minus; which has been tested in a number of clinical trials, with exciting results. All the data from worldwide clinical trials confirm that eculizumab radically modifies the symptoms, the biology, and the natural history of PNH, strongly improving the quality of life of PNH patients.Keywords: paroxysmal nocturnal hemoglobinuria, GPI-AP, PIG-A, complement, eculizumab Antonio M RisitanoBruno RotoliDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2008, Iss Issue 2, Pp 205-222 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Antonio M Risitano Bruno Rotoli Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents
description	Antonio M Risitano, Bruno RotoliHematology, Department of Biochemistry and Medical Biotechnologies, Federico II University of Naples, ItalyAbstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal non-malignant hematological disease characterized by the expansion of hematopoietic stem cells (HSCs) and progeny mature cells, whose surfaces lack all the proteins linked through the glycosyl-phosphatidyl inositol anchor. This defect arises from an acquired somatic mutation in the X-linked phosphatidyl-inositol glycan class A gene, with subsequent clonal expansion of the mutated HSCs as a result of a concomitant, likely immune-mediated, selective pressure. The disease is characterized by complement-mediated chronic intravascular hemolysis, resulting in hemolytic anemia and hemosiderinuria; capricious exacerbations lead to recurrent gross hemoglobinuria. Additional cardinal manifestations of PNH are a variable degree of bone marrow failure and an intrinsic propensity to thromboembolic events. The disease is markedly invalidating, with chronic symptoms requiring supportive therapy &minus; usually including periodical transfusions; possible life-threatening complications may also ensue. The biology of PNH has been progressively elucidated in the past few years, but therapeutic strategies remained unsatisfactory for decades, the only exception being stem cell transplantation, which is restricted to selected patients and retains significant morbidity and mortality. Recently, a biological agent to treat PNH has been developed &minus; the terminal complement inhibitor eculizumab &minus; which has been tested in a number of clinical trials, with exciting results. All the data from worldwide clinical trials confirm that eculizumab radically modifies the symptoms, the biology, and the natural history of PNH, strongly improving the quality of life of PNH patients.Keywords: paroxysmal nocturnal hemoglobinuria, GPI-AP, PIG-A, complement, eculizumab
format	article
author	Antonio M Risitano Bruno Rotoli
author_facet	Antonio M Risitano Bruno Rotoli
author_sort	Antonio M Risitano
title	Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents
title_short	Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents
title_full	Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents
title_fullStr	Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents
title_full_unstemmed	Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents
title_sort	paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents
publisher	Dove Medical Press
publishDate	2008
url	https://doaj.org/article/a0269f5c0eeb49e3abdebbb0ea43c018
work_keys_str_mv	AT antoniomrisitano paroxysmalnocturnalhemoglobinuriapathophysiologynaturalhistoryandtreatmentoptionsintheeraofbiologicalagents AT brunorotoli paroxysmalnocturnalhemoglobinuriapathophysiologynaturalhistoryandtreatmentoptionsintheeraofbiologicalagents
_version_	1718401094671925248

Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents

Ejemplares similares