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The main symptoms of this disease such as abdominal pain, renal failure or pulmonary hypertension and even the basis of the dramatic thrombophilia can be related to intravascular haemolysis and liberation of free haemoglobin resulting in <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> depletion. In addition, there has been a recent great progress in elucidating the pathophysiology of clonal expansion within <jats:styled-content style=\"fixed-case\">PNH<\/jats:styled-content> bone marrow. In the majority of patients with haemolytic <jats:styled-content style=\"fixed-case\">PNH<\/jats:styled-content>, there are additional mutations within genes beyond <jats:styled-content style=\"fixed-case\">PIG<\/jats:styled-content>\u2010A and rather affecting growth and differentiation of clonal bone marrow cells. In contrast to the formerly proposed single mechanism hypotheses such as immune selection or intrinsic gain of clonal dominance, this appears to follow a pattern of a complex clonal hierarchy putatively integrating both earlier anticipated mechanisms. Treatment of <jats:styled-content style=\"fixed-case\">PNH<\/jats:styled-content> is mainly supportive. The only curative approach as allogeneic stem cell transplantation should only be applied to patients with complications such as secondary bone marrow aplasia or transformation into <jats:styled-content style=\"fixed-case\">MDS<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>. Symptomatic haemolytic <jats:styled-content style=\"fixed-case\">PNH<\/jats:styled-content> will be treated with eculizumab, an inhibitor of the terminal complement cascade. Treatment with eculizumab can significantly prevent <jats:styled-content style=\"fixed-case\">PNH<\/jats:styled-content>\u2010related symptoms including the abnormal thrombophilia. Recently, it was demonstrated that in contrast to untreated historic <jats:styled-content style=\"fixed-case\">PNH<\/jats:styled-content> patients, meanwhile a normal life expectancy is observed in eculizumab\u2010treated patients. The recently approved vaccine against meningococci type B by the European Medical Agency (<jats:styled-content style=\"fixed-case\">EMA<\/jats:styled-content>) could probably further help to prevent meningococcal sepsis due to the induced complement deficiency by eculizumab.<\/jats:p>","DOI":"10.1111\/ejh.12520","type":"journal-article","created":{"date-parts":[[2015,2,21]],"date-time":"2015-02-21T13:58:56Z","timestamp":1424527136000},"page":"464-473","source":"Crossref","is-referenced-by-count":26,"title":["Update on paroxysmal nocturnal haemoglobinuria: on the long way to understand the principles of the disease"],"prefix":"10.1111","volume":"94","author":[{"given":"J\u00f6rg","family":"Schubert","sequence":"first","affiliation":[{"name":"Internal Medicine II Elblandklinikum Riesa Riesa Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"R\u00f6th","sequence":"additional","affiliation":[{"name":"Department of Haematology West German Cancer 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