Erroneous determination of hyperphosphatemia ('pseudohyperphosphatemia') in sera of patients that have been treated with liposomal amphotericin B (AmBisome).
BACKGROUND
Hyperphosphatemia is not an expected consequence of dosing with amphotericin B formulations. However, hyperphosphatemia or pseudohyperphosphatemia (erroneously high phosphorous measurements) has been variously reported in a number of recent case studies associated with liposomal amphotericin B (L-AmB, AmBisome®). In some of these cases, hyperphosphatemia was assumed to obtain, and direct treatment or alterations to antifungal therapy were carried out. In other cases, pseudohyperphosphatemia was assumed to obtain.


METHODS
Using two different Beckman-Coulter measurement platforms (Synchron® LX20 with PHOSm or PHS chemistry systems) phosphorus values were obtained in human serum titrated with L-AmB or L-AmB placebo (identical composition to L-AmB, but without the drug molecule present).


RESULTS
We demonstrate an L-AmB specific assay interference with the PHOSm chemistry system resulting in a linear (in amphotericin B) upward shift in phosphorus values (pseudohyperphosphatemia) and owing to an L-AmB specific interference with the mannitol containing assay system. Interference is not seen with L-AmB placebo. The PHS chemistry exhibits a minor interference from L-AmB, and it is in the form of lower assay values. L-AmB spiked sera treated with LipoClear* or subjected to ultrafiltration exhibit correct phosphorous values.


CONCLUSIONS
We demonstrate L-AmB specific assay interference with the PHOSm chemistry system resulting in pseudohyperphosphatemia and owing to an L-AmB dependent alteration in the kinetic performance of the reagent system. The PHS chemistry system exhibits lesser interference from L-AmB, and it is in the form of lower assay values. Two methods of generating reliable phosphorus data (use of LipoClear or the Microcon-30) are provided.
Jensen
Gerard M
GM
Gilead Sciences Inc., 650 Cliffside Drive, San Dimas, CA, 91773, United States. gjensen@gilead.com
Bunch
Tarquinus H
TH
Wolf
Steven
S
Laybourne
Stefanie
S
D000666:Amphotericin B / Q000097:blood / Q000627:therapeutic use*; D016477:Artifacts; D001774:Blood Chemical Analysis / Q000379:methods*; D003951:Diagnostic Errors; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood* / Q000175:diagnosis*; D010758:Phosphorus / Q000097:blood / Q000737:chemistry
C068538:liposomal amphotericin B; D010758:Phosphorus; D000666:Amphotericin B