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 fac tor (Mpl ligand). The receptor for this platelet growth factor (Mpl) is exp ressed on the platelet surface membrane. A recombinant thrombopoietic cytok ine, 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 benefi cial or adverse effect on the development of the platelet storage lesion du ring 5 days of storage. STUDY DESIGN AND METHODS: This study was designed as a dose-response protoc ol to determine the effects of adding increasing concentrations of PEG-rHuM GDF (0.0 [control], 2.5, 25, and 250 ng/mL) to apheresis platelets stored i n two types of plastic storage containers. The increasing concentrations of PEG-rHuMGDF used simulated the theoretical peak plasma level attained in v ivo, with an intravenous dose of 0, 0.1, 1.0 and 10 mu g per kg of PEG-rHuM GDF. The platelets were stored with agitation at 20 to 24 degrees C for 5 d ays. A battery of in vitro assays was performed on storage Days 1 and 5, in cluding pH, blood gases, platelet count, lactate dehydrogenase, mean platel et 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-rH uMGDF doses studied or the control. Storage-induced changes, however, did o ccur equally in all four groups of platelets over the 5 days of storage. CONCLUSION: The addition to stored apheresis platelets of up to 10 mu g per kg of PEG-rHuMGDF (250 ng/mL), followed by 5 days of storage at standard c onditions, does not appear to promote or retard development of the platelet storage lesion.