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Published on: January 2, 2013
In vitro interference of the red cell substitute pyridoxalated hemoglobin-polyoxyethylene with blood compatibility,
G L Alonsozana1, M D Elfath, C Mackenzie
1Department of Pathology, School of Medicine, University of Maryland at Baltimore, USA.
Objectives:
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.
Design:
In vitro studies.
Setting:
University hospital laboratory.
Participants:
Four healthy volunteers, blood types A, B, AB, and O. All were Rh+.
Measurements And Main 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.
Insights
Pyridoxalated hemoglobin-polyoxyethylene (PHP), a red cell substitute, can cause red blood cell aggregation. While blood compatibility testing is unaffected, liver function tests require alternative methods when using PHP.
Area of Science:
- Biomedical Engineering
- Hematology
- Clinical Chemistry
Background:
- Pyridoxalated hemoglobin-polyoxyethylene (PHP) is an investigational red blood cell substitute.
- PHP has shown dose-dependent red blood cell aggregation and rouleaux formation in vitro.
- The impact of PHP on laboratory testing requires thorough evaluation for clinical application.
Purpose of the Study:
- To assess the effects of PHP on blood compatibility testing.
- To determine the interference of PHP with routine coagulation and clinical chemistry assays.
- To evaluate the reliability of laboratory measurements in the presence of PHP.
Main Methods:
- In vitro studies were conducted using blood samples from four healthy volunteers.
- Blood compatibility tests (ABO typing, Rh typing, antibody screening) and coagulation studies were performed on blood mixed with PHP at 1, 2, and 4 g/dL concentrations.
- Clinical chemistry interference was assessed by adding analytes to a serum matrix containing PHP.
Main Results:
- PHP caused dose-dependent red blood cell aggregation and rouleaux formation, particularly at 4 g/dL.
- Saline replacement corrected rouleaux, ensuring accurate ABO and Rh typing and antibody screening.
- Coagulation tests (PTT, PT, fibrinogen) and most clinical chemistry analytes (electrolytes, renal function, cardiac markers) showed no significant interference.
- Liver function tests yielded unacceptable results in the presence of PHP.
Conclusions:
- PHP-induced red blood cell aggregation does not impede standard blood compatibility testing due to effective saline correction.
- Routine blood banking, coagulation assays, and most clinical chemistry measurements are reliable with PHP.
- Alternative methods are necessary for accurate liver function assessment when using PHP.
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