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Paroxysmal nocturnal haemoglobinuria treatment with eculizumab is associated with a positive direct antiglobulin test
Author(s) -
Höchsmann B.,
Leichtle R.,
von Zabern I.,
Kaiser S.,
Flegel W. A.,
Schrezenmeier H.
Publication year - 2012
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/j.1423-0410.2011.01530.x
Subject(s) - eculizumab , medicine , haemolysis , population , gastroenterology , monoclonal , coombs test , immunology , antibody , monoclonal antibody , complement system , environmental health
Background/Objectives Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by intravascular haemolysis with a negative direct antiglobulin test (DAT). Eculizumab is a humanized monoclonal antibody that inhibits complement component C5 and is approved for PNH treatment. Recent publications demonstrated that some patients with PNH develop a positive DAT during eculizumab treatment. These published clinical trials investigated a highly selected patient population. Therefore, it seems important to study this topic in a general PNH patient population with a longer follow‐up. Materials and Methods We analysed haemolytic activity, RBC transfusion requirement, effect on DAT and ferritin levels in 41 patients with PNH before and during eculizumab therapy with a median follow‐up of 24 months (range 1–63 months). Results During eculizumab therapy, median LDH decreased (1657–258 U/l; P < 0·0001), while median haemoglobin increased (9·2–10·3 g/dl). Eighteen of 32 pts (56%) who previously required regular transfusions became transfusion independent. DAT was positive for C3d in 72·4% of 21 eculizumab‐treated pts with available DAT. Ferritin levels increased (69–348 ng/ml, P < 0·0001). This increase was more pronounced in pts with ongoing transfusion dependency during eculizumab therapy. Conclusion Eculizumab therapy for PNH should be added to the list of possible causes for a positive DAT. Intravascular haemolysis was inhibited by eculizumab, but signs of extravascular haemolysis should be monitored. Because renal iron loss was stopped, eculizumab‐treated pts can be prone to iron overload and therefore ferritin concentrations should be monitored closely.