title: Production of pathogen-inactivated RBC concentrates using PEN110 chemistry: a Phase I clinical study.
abstract: BACKGROUND
  Despite extensive reductions in risk, donor selection and testing cannot eliminate pathogen transmission. The objective of this study was to evaluate clinically the viability of pathogen-inactivated RBCs.
  
  
  METHODS
  Twelve healthy subjects each donated two units of blood that were handled as additive system control units or were inactivated using the PEN110 process (INACTINE, V.I. Technologies) in randomized order. PEN110, which inactivates pathogens by reacting with nucleic acid bases, was incubated with RBCs for 6 hours, followed by washing and quenching with sodium thiosulfate. Radiolabeled RBC recovery and survival determinations were undertaken after 28 days of storage; biochemical and hematologic variables were assessed over 42 days.
  
  
  RESULTS
  After 28 days, treated units had a 24-hour double-label ((51)Cr/(99m)Tc) recovery (85.0 +/- 5.0%) that was indistinguishable from control units (85.9 +/- 2.7%); the times required for reduction of radioactivity of labeled cells to half the Day 1 activity (T(50)) were similar for both groups (treated, 31.9 +/- 8.2 days; control, 32.9 +/- 3.3 days). No deleterious effects of PEN110 treatment were found on RBC antigens tested. Treatment reduced 2,3-DPG levels by half and slightly lowered pH levels. Throughout the 42-day storage period, treated RBCs had a lower level of lactate production and a trend toward lower glucose consumption. Hemolysis remained below 1 percent; supernatant potassium and ATP levels were lower than those seen in control RBCs.
  
  
  CONCLUSIONS
  PEN110-treated RBCs stored for 28 days meet all critical requirements for therapeutically useful units.
authors.affiliation: Cell Labeling Laboratory, Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: AuBuchon
authors.forename: Constance A
authors.initials: CA
authors.lastname: Pickard
authors.forename: Louise H
authors.initials: LH
authors.lastname: Herschel
authors.forename: Jill C
authors.initials: JC
authors.lastname: Roger
authors.forename: James E
authors.initials: JE
authors.lastname: Tracy
authors.forename: Andrei
authors.initials: A
authors.lastname: Purmal
authors.forename: John
authors.initials: J
authors.lastname: Chapman
authors.forename: Samuel
authors.initials: S
authors.lastname: Ackerman
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Beach
mesh_terms: D019794:2,3-Diphosphoglycerate / Q000097:blood; D000017:ABO Blood-Group System / Q000032:analysis; D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D001782:Blood Donors; D001786:Blood Glucose / Q000032:analysis; D001793:Blood Preservation; D018592:Cross-Over Studies; D004203:Disinfection; D004905:Erythrocyte Aging / Q000187:drug effects; D004912:Erythrocytes / Q000737:chemistry* / Q000502:physiology* / Q000821:virology; D005260:Female; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D012204:Rh-Hr Blood-Group System / Q000032:analysis
chemical_list: D000017:ABO Blood-Group System; D001786:Blood Glucose; C451719:PEN 110; D011073:Polyamines; D012204:Rh-Hr Blood-Group System; D019794:2,3-Diphosphoglycerate; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D011188:Potassium