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DOI: 10.1055/s-0028-1124013
© Georg Thieme Verlag KG Stuttgart · New York
Paroxysmale nächtliche Hämoglobinurie (PNH)
Pathogenese, Diagnostik und TherapieParoxysmal nocturnal hemoglobinuria (PNH)Pathogenesis, diagnosis and treatmentPublication History
eingereicht: 26.6.2008
akzeptiert: 27.11.2008
Publication Date:
17 February 2009 (online)
![](https://www.thieme-connect.de/media/dmw/200909/lookinside/thumbnails/10.1055-s-0028-1124013-1.jpg)
Zusammenfassung
Die PNH ist klinisch durch eine Trias aus hämolytischer Anämie, Thrombophilie und Zytopenie gekennzeichnet. Ursache der PNH ist eine Mutation des PIG (Phosphatidyl-Inositol-Glykan)-A-Gens der pluripotenten hämatopoetischen Stammzelle, wodurch es zum Verlust des GPI (Glykosylphosphatidylinositol)-Ankers und entsprechend verankerter Proteine auf der Oberfläche der betroffenen Zellreihen kommt. Die Diagnose wird mit Hilfe der Durchflusszytometrie gestellt, wodurch auch Art und Größe des PNH-Klons bestimmt werden können. Im Vordergrund steht die symptomatische Therapie. Bei schweren Verläufen bietet die allogene Knochenmarktransplantation eine kurative Option. Einen neuen Ansatz in der Behandlung der PNH stellt die Hemmung des terminalen Komplement-Weges durch einen monoklonalen Antikörper (Eculizumab) dar. Hierdurch konnte in Studien die Komplement-vermittelte intravasale Hämolyse gehemmt, der Transfusionsbedarf gesenkt, die Lebensqualität der Patienten verbessert und auch das Risiko für thromboembolische Ereignisse gesenkt werden, welche die Haupttodesursache der PNH darstellen.
Summary
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the classic clinical triad of corpuscular hemolytic anemia, thrombophilia and cytopenia. This is caused by an acquired mutation of the PIG(phosphatidylinositol glycan)-A gene of the pluripotent hematopoetic stem cell. This results in a deficiency of GPI(glycosylphosphatidylinositol)-anchors and GPI-anchored proteins on the surface of affected blood cells. Flow cytometry is the standard for diagnosis and measurement of type and size of the PNH clone. Treatment of PNH is mainly symptomatic. Allogeneic bone marrow transplantation is the only curative option in case of severe complications during the course of the diseases. A new targeted treatment strategy is the inhibition of the terminal complement cascade with a monoclonal antibody (eculizumab). As shown in clinical studies this is efficient to reduce complement mediated intravascular hemolysis, reduce the need for transfusions, improve the quality of life in patients with PNH and reduce the risk for thromboembolic complications, which are the main cause of mortality in PNH.
Schlüsselwörter
paroxysmale nächtliche Hämoglobinurie - korpuskuläre hämolytische Anämie - Komplementinhibition - Eculizumab
Keywords
paroxysmal nocturnal hemoglobinuria - corpuscular hemolytic anemia - complement inhibition - eculizumab
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Dr. med. Alexander Röth
Universitätsklinikum Essen, Universität
Duisburg-Essen
Hufelandstr. 55
45122 Essen
Phone: 0201/723-84219
Fax: 0201/723-5934
Email: alexander.roeth@uni-due.de