Effect of recombinant human megakaryocyte growth and development factor coupled with polyethylene glycol on the platelet storage lesion.
BACKGROUND
Platelet production is regulated by a thrombopoietic growth factor (Mpl ligand). The receptor for this platelet growth factor (Mpl) is expressed on the platelet surface membrane. A recombinant thrombopoietic cytokine, recombinant human megakaryocyte growth and development factor coupled with polyethylene glycol (PEG-rHuMGDF), was added to apheresis platelets in vitro to determine whether Mpl ligand-receptor binding produced any beneficial or adverse effect on the development of the platelet storage lesion during 5 days of storage.


METHODS
This study was designed as a dose-response protocol to determine the effects of adding increasing concentrations of PEG-rHuMGDF (0.0 [control], 2.5, 25, and 250 ng/mL) to apheresis platelets stored in two types of plastic storage containers. The increasing concentrations of PEG-rHuMGDF used simulated the theoretical peak plasma level attained in vivo, with an intravenous dose of 0, 0.1, 1.0 and 10 microg per kg of PEG-rHuMGDF. The platelets were stored with agitation at 20 to 24 degrees C for 5 days. A battery of in vitro assays was performed on storage Days 1 and 5, including pH, blood gases, platelet count, lactate dehydrogenase, mean platelet volume, glucose, lactate, osmotic recovery, morphology score, CD62P, and one-dimensional polyacrylamide gel electrophoresis analyses.


RESULTS
Analysis of results on both Day 1 and Day 5 showed no significant differences among any of the three PEG-rHuMGDF doses and the control group, for any in vitro assay. One-dimensional polyacrylamide gel electrophoresis showed no changes among the platelet protein patterns for the three PEG-rHuMGDF doses studied or the control. Storage-induced changes, however, did occur equally in all four groups of platelets over the 5 days of storage.


CONCLUSIONS
The addition to stored apheresis platelets of up to 10 microg per kg of PEG-rHuMGDF (250 ng/mL), followed by 5 days of storage at standard conditions, does not appear to promote or retard development of the platelet storage lesion.
Snyder
E
E
Blood Bank and the Department of Laboratory Medicine, Yale University School of Medicine, Yale-New Haven Hospital, Connecticut 06504, USA.
Perrotta
P
P
Rinder
H
H
Baril
L
L
Nichol
J
J
Gilligan
D
D
D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D001793:Blood Preservation; D048429:Cell Size; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007773:Lactates / Q000097:blood; D019007:P-Selectin / Q000032:analysis; D010983:Plateletpheresis; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology*
D001786:Blood Glucose; D007773:Lactates; D019007:P-Selectin; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin; D007770:L-Lactate Dehydrogenase