Die paroxysmale nächtliche Hämoglobinurie - ein erworbener genetischer Defekt der hämatopoietischen Stammzelle<sup>*</sup>

Schubert, Jörg; Ostendorf, Tammo; Nischan, Claudia; Re, Schmidt

doi:10.1055/s-2008-1043195

Cited by 2 publications

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“…As human red cells do not express CD46, a transmembranous complement regulator, the deficiency of GPI‐linked surface proteins such as CD55 and CD59 will lead to a complete lack of complement inhibiting surface proteins on red cells and platelets. Thus, affected cells will be lysed by an unregulated activation especially of the alternative complement cascade . GPI deficiency in PNH is a result of an acquired mutation within the PIG‐A gene coding for an enzyme involved in the first step of biosynthesis of the GPI‐anchor molecule .…”

Section: Pathophysiologymentioning

confidence: 99%

Update on paroxysmal nocturnal haemoglobinuria: on the long way to understand the principles of the disease

Schubert¹,

Röth

2015

European J of Haematology

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The understanding of the clinical manifestations in paroxysmal nocturnal haemoglobinuria (PNH) has made great progress. 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 NO depletion. In addition, there has been a recent great progress in elucidating the pathophysiology of clonal expansion within PNH bone marrow. In the majority of patients with haemolytic PNH, there are additional mutations within genes beyond PIG-A 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 PNH 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 MDS or AML. Symptomatic haemolytic PNH will be treated with eculizumab, an inhibitor of the terminal complement cascade. Treatment with eculizumab can significantly prevent PNH-related symptoms including the abnormal thrombophilia. Recently, it was demonstrated that in contrast to untreated historic PNH patients, meanwhile a normal life expectancy is observed in eculizumab-treated patients. The recently approved vaccine against meningococci type B by the European Medical Agency (EMA) could probably further help to prevent meningococcal sepsis due to the induced complement deficiency by eculizumab.

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Section: Pathophysiologymentioning

confidence: 99%

Update on paroxysmal nocturnal haemoglobinuria: on the long way to understand the principles of the disease

Schubert¹,

Röth

2015

European J of Haematology

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Immunsystem, Infektion und Abwehr

Schmidt¹

2000

Springer Lehrbuch

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Die paroxysmale nächtliche Hämoglobinurie - ein erworbener genetischer Defekt der hämatopoietischen Stammzelle^*

Cited by 2 publications

References 0 publications

Update on paroxysmal nocturnal haemoglobinuria: on the long way to understand the principles of the disease

Update on paroxysmal nocturnal haemoglobinuria: on the long way to understand the principles of the disease

Immunsystem, Infektion und Abwehr

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Die paroxysmale nächtliche Hämoglobinurie - ein erworbener genetischer Defekt der hämatopoietischen Stammzelle*

Cited by 2 publications

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Update on paroxysmal nocturnal haemoglobinuria: on the long way to understand the principles of the disease

Update on paroxysmal nocturnal haemoglobinuria: on the long way to understand the principles of the disease

Immunsystem, Infektion und Abwehr

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Die paroxysmale nächtliche Hämoglobinurie - ein erworbener genetischer Defekt der hämatopoietischen Stammzelle^*