title: Paroxysmal nocturnal haemoglobinuria treatment with eculizumab is associated with a positive direct antiglobulin test.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Wuerttemberg, Hessen, Germany. b.hoechsmann@blutspende.de
authors.forename: B
authors.initials: B
authors.lastname: Höchsmann
authors.forename: R
authors.initials: R
authors.lastname: Leichtle
authors.forename: I
authors.initials: I
authors.lastname: von Zabern
authors.forename: S
authors.initials: S
authors.lastname: Kaiser
authors.forename: W A
authors.initials: WA
authors.lastname: Flegel
authors.forename: H
authors.initials: H
authors.lastname: Schrezenmeier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002648:Child; D005260:Female; D005293:Ferritins / Q000097:blood / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D005293:Ferritins; C481642:eculizumab; D007770:L-Lactate Dehydrogenase