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Journal of Laboratory Medicine

Official Journal of the German Society of Clinical Chemistry and Laboratory Medicine

Editor-in-Chief: Schuff-Werner, Peter

Ed. by Ahmad-Nejad, Parviz / Bidlingmaier, Martin / Bietenbeck, Andreas / Conrad, Karsten / Findeisen, Peter / Fraunberger, Peter / Ghebremedhin, Beniam / Holdenrieder, Stefan / Kiehntopf, Michael / Klein, Hanns-Georg / Kohse, Klaus P. / Kratzsch, Jürgen / Luppa, Peter B. / Meyer, Alexander von / Nebe, Carl Thomas / Orth, Matthias / Röhrig-Herzog, Gabriele / Sack, Ulrich / Steimer, Werner / Weber, Thomas / Wieland, Eberhard / Winter, Christoph / Zettl, Uwe K.


IMPACT FACTOR 2017: 0.216

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Volume 39, Issue 2

Issues

Paroxysmal nocturnal hemoglobinuria revisited: news on pathophysiology, clinical course and treatment

Paroxysmale nächtliche Hämoglobinurie: neue Erkenntnisse zur Pathophysologie, klinischem Verlauf und Behandlung

Sixten Körper
  • Corresponding author
  • Institut für Klinische Transfusionsmedizin und Immungenetik Ulm, DRK-Blutspendedienst Baden-Württemberg – Hessen und Universitätsklinikums Ulm, Ulm, Germany
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/ Britta Höchsmann
  • Institut für Klinische Transfusionsmedizin und Immungenetik Ulm, DRK-Blutspendedienst Baden-Württemberg – Hessen und Universitätsklinikums Ulm, Ulm, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Hubert Schrezenmeier
  • Institut für Klinische Transfusionsmedizin und Immungenetik Ulm, DRK-Blutspendedienst Baden-Württemberg – Hessen und Universitätsklinikums Ulm, Ulm, Germany
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Published Online: 2015-03-25 | DOI: https://doi.org/10.1515/labmed-2015-0010

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare benign clonal disorder of hematopoiesis. Its etiologic basis is the clonal dominance of a PIGA-mutated hematopoietic progenitor that gives rise to GPI-deficient blood cells that are unable to express complement inhibitors like CD55 or CD59. These cells are prone to complement-induced hemolysis. In classic hemolytic PNH, granulocyte clone sizes can be up to 90% or more. Much progress has been made during the last years in understanding the interrelations of complement-dependent hemolysis; its consequences like thrombosis, renal failure or pulmonal hypertension; and possible treatment strategies. To gain clinical relevance, the PNH clone has to make a relevant contribution to blood cell generation; however, a minimal clone size as a threshold for the occurrence of symptoms such as thrombosis, dyspnea, chest or abdominal pain cannot be given. Such symptoms can be seen in a relevant proportion of patients with clone size smaller than 10%. The driver for the clonal dominance of the PIGA-mutated hematopoiesis is still not clear. Recently, data about coexisting mutations in cancer genes have been published and new mechanisms for autoimmunity have been presented. The success of eculizumab in the treatment of PNH patients has stimulated the development of a variety of new strategies for complement inhibition. This review will focus on the most important findings in pathophysiology, clinical course and treatments during the last years.

Zusammenfassung

Die paroxysmale nächtliche Hämoglobinurie (PNH) ist eine seltene gutartige klonale Erkrankung der Blutbildung. Ursache für die PNH ist eine klonale Dominanz von hämatopoietischen Progenitorzellen aus welchen Blutzellen entstehen, bei denen komplementinhibitorischen Proteine wie CD55 oder CD59 nicht exprimiert werden können. Solche Zellen sind anfällig gegenüber komplementvermittelter Hämolyse. Die klassische hämolytische PNH zeigt Granulozytenklongrößen von 90% und mehr. In den letzten Jahren haben wir viel über den Zusammenhang zwischen komplementvermittelter Hämolyse und ihrer klinischen Konsequenzen wie Thrombose, Niereninsuffizienz oder Pulmonale Hypertension und möglicher Behandlungsstrategien gelernt. Um klinisch relevant zu werden muss der PNH-Klon einen relevanten Beitrag zur Blutbildung leisten. Eine Schwellenwert für die klinische Relevanz eines PNH-Klons kann nicht angegeben werden, da auch kleine Klone Symptome wie Thrombosen, Dyspnoe, thorakale oder abdominelle Schmerzen verursachen können. Solche Symptome treten mit einen relevanten Anteil auch bei Patienten mit Klongrößen, die kleiner als 10% sind auf. Der Auslöser für die Entstehung der klonalen Dominanz ist bislang nicht geklärt. Kürzlich wurde gezeigt, dass unterschiedliche Mutationen von Genen in PNH-Klonen gefunden werden, die auch bei hämatologischen Neoplasien vorkommen. Auch neue Autoimmunmechanismen wurden beschrieben. Der Erfolg von Eculizumab in der Behandlung von PNH-Patienten hat die Entwicklung von neuen Komplementinhibitoren angeregt. Dieser Review fokusiert auf die wichtigsten Erkenntnisse der letzten Jahre auf dem Gebiet der Patophysiologie, dem klinischen Verlauf und der Therapie der PNH.

Reviewed publication

OrthM.

Keywords: complement inhibitors; eculizumab; paroxysmal nocturnal hemoglobinuria; pathophysiology; therapy

Schlüsselwörter:: Eculizumab; komplementinhibitorischen Proteine; paroxysmale nächtliche Hämoglobinurie; Pathophysiologie; Therapie

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About the article

Correspondence: Sixten Körper, Institut für Klinische Transfusionsmedizin und Immungenetik Ulm, DRK-Blutspendedienst Baden-Württemberg – Hessen und Universitätsklinikums Ulm, Helmholtzstraße 10, 89081 Ulm, Germany, E-Mail:


Received: 2015-01-19

Accepted: 2015-02-20

Published Online: 2015-03-25

Published in Print: 2015-04-01


Citation Information: LaboratoriumsMedizin, Volume 39, Issue 2, Pages 87–96, ISSN (Online) 1439-0477, ISSN (Print) 0342-3026, DOI: https://doi.org/10.1515/labmed-2015-0010.

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