title: In vitro interference of the red cell substitute pyridoxalated hemoglobin-polyoxyethylene with blood compatibility, coagulation, and clinical chemistry testing.
abstract: OBJECTIVE
  Pyridoxalated hemoglobin-polyoxyethylene (PHP) is a prototypical red cell substitute approved for phase I studies. Peripheral blood smears of human blood mixed with PHP in 1 to 4 g/dL concentrations showed dose-dependent red cell aggregation and rouleaux. Whether this aggregation limits interpretation of blood compatibility testing and whether the intense coloration of serum or plasma containing PHP affects routine coagulation and clinical chemistry measurements was tested.
  
  
  METHODS
  In vitro studies.
  
  
  METHODS
  University hospital laboratory.
  
  
  METHODS
  Four healthy volunteers, blood types A, B, AB, and O. All were Rh+.
  
  
  RESULTS
  ABO typing, Rh typing, and antibody screening and coagulation studies were performed on blood: PHP admixtures having final concentrations of 1, 2, and 4 g/dL. For clinical chemistry interference studies, known concentrations of analytes were added to a serum matrix containing PHP. ABO (forward) and Rh typing showed no interference in the three concentrations tested. Reverse ABO typing and antibody screening showed rouleaux at 4 g/dL, which corrected with routine saline replacement. Partial thromboplastin time (PTT), prothrombin time (PT), and fibrinogen showed no clinically significant differences from the controls. Results for electrolytes, renal function analytes, and markers of cardiac injury were acceptable by standard laboratory methods. However, results of liver function tests were unacceptable in PHP-containing specimens.
  
  
  CONCLUSIONS
  PHP-induced aggregation was observed with high PHP concentration; however, compatibility testing was not affected because agglutination was corrected by saline replacement, which is standard practice. Although routine blood banking, coagulation, and most clinical chemistry analytes can be measured reliably, alternative methods and strategies are needed for assessing liver function in the presence of PHP.
authors.affiliation: Department of Pathology, School of Medicine, University of Maryland at Baltimore, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Alonsozana
authors.forename: M D
authors.initials: MD
authors.lastname: Elfath
authors.forename: C
authors.initials: C
authors.lastname: Mackenzie
authors.forename: L C
authors.initials: LC
authors.lastname: Gregory
authors.forename: S H
authors.initials: SH
authors.lastname: Duh
authors.forename: B
authors.initials: B
authors.lastname: Trump
authors.forename: R H
authors.initials: RH
authors.lastname: Christenson
mesh_terms: D001777:Blood Coagulation; D001788:Blood Grouping and Crossmatching; D001802:Blood Substitutes / Q000494:pharmacology*; D002624:Chemistry, Clinical; D006454:Hemoglobins / Q000494:pharmacology*; D006801:Humans; D011092:Polyethylene Glycols / Q000494:pharmacology*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C050907:pyridoxalated-hemoglobin-polyethylene glycol conjugate; D011092:Polyethylene Glycols