title: Universal pooled plasma (Uniplas(®)) does not induce complement-mediated hemolysis of human red blood cells in vitro.
abstract: BACKGROUND
  Pooling of plasma of different blood groups before large scale manufacturing of Uniplas(®) results in the formation of low levels of soluble immune complexes (CIC). The aim of this study was to investigate the level and removal of CIC during Uniplas(®) manufacturing. In addition, an in vitro hemolysis assay should be developed and investigate if Uniplas(®) does induce complement-mediated hemolysis of human red blood cells (RBC).
  
  
  METHODS
  In-process samples from Uniplas(®) (universal plasma) and Octaplas(LG)(®) (blood group specific plasma) routine manufacturing batches were tested on CIC using commercially available ELISA test kits. In addition, CIC was produced by admixing heat-aggregated immunoglobulins or monoclonal anti-A/anti-B antibodies to plasma and removal of CIC was followed in studies of the Uniplas(®) manufacturing process under down-scale conditions. The extent of RBC lysis was investigated in plasma samples using the in-house hemolysis assay.
  
  
  RESULTS
  Levels of CIC in Uniplas(®) are within the normal ranges for plasma and comparable to that found in Octaplas(LG)(®). Down-scale experiments showed that both IgG/IgM-CIC levels are significantly removed on average by 40-50% during Uniplas(®) manufacturing. Uniplas(®) does not induce hemolysis of RBCs in vitro. Hemolysis occurs only after spiking with high titers of anti-A/anti-B antibodies and depends on the antibody specificity (i.e. titer) in the plasma sample.
  
  
  CONCLUSIONS
  The results of this study confirm the safety of Uniplas(®) regarding transfusion to patients of all ABO blood groups.
authors.affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H, Research & Development, Oberlaaer Strasse 235, A-1100 Vienna, Austria. Electronic address: andrea.heger@octapharma.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Heger
authors.affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H, Research & Development, Oberlaaer Strasse 235, A-1100 Vienna, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Brandstätter
authors.affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H, Research & Development, Oberlaaer Strasse 235, A-1100 Vienna, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Prager
authors.affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H, Research & Development, Oberlaaer Strasse 235, A-1100 Vienna, Austria.
authors.forename: Janja
authors.initials: J
authors.lastname: Brainovic
authors.affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H, Research & Development, Oberlaaer Strasse 235, A-1100 Vienna, Austria.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Cortes
authors.affiliation: Octapharma Pharmazeutika Produktionsges.m.b.H, Research & Development, Oberlaaer Strasse 235, A-1100 Vienna, Austria.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Römisch
mesh_terms: D000017:ABO Blood-Group System / Q000097:blood / Q000737:chemistry; D000936:Antigen-Antibody Complex / Q000097:blood / Q000737:chemistry; D004912:Erythrocytes / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D005260:Female; D006461:Hemolysis; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000737:chemistry; D008297:Male; D010949:Plasma / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000017:ABO Blood-Group System; D000936:Antigen-Antibody Complex; D007518:Isoantibodies
keywords: CIC; Functional assay; In vitro hemolysis; Soluble immune complexes; Uniplas; Universal plasma