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Recombinant human megakaryocyte growth and development factor attenuates postbypass thrombocytopenia
Masanori Nakamura, MD, Christopher F Toombs, PhD, Ignacio G Duarte, MD, Russell S Ronson, MD, L.Susan Schmarkey, BS, Sara L Katzmark, BS, Jill Robinson, BS, Dirck L Dillehay, PhD, Jakob Vinten-Johansen, PhD, Robert A Guyton, MD The Annals of Thoracic Surgery Volume 66, Issue 4, Pages (October 1998) DOI: /S (98)
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Fig 1 Plasma concentration of c-mpl ligand (endogenous megakaryocyte growth and development factor plus polyethylene glycol derived recombinant human megakaryocyte growth and development factor [PEG-rHuMGDF]) during the course of the experiment. The plasma level of c-mpl ligand was significantly increased in the PEG-rHuMGDF group before the operation (Pre Op) and 1 hour after the operation (Po 1 h). However, plasma titers were less than 3 ng/mL, a level at which PEG-rHuMGDF does not affect platelet function. (Po = postoperative; ∗p < 0.05 versus previous time in PEG-rHuMGDF; +p < 0.05 between groups.) The Annals of Thoracic Surgery , DOI: ( /S (98) )
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Fig 2 Immediately before (Pre Op) and after (Po 1 hr) extracorporeal circulation, the hematocrit (Hct) was significantly decreased relative to the previous time point. However, Hct was comparable between the groups throughout the experiment, suggesting there was no difference in the degree of hemodilution and no effect of polyethylene glycol derived recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on the erythrocyte population. (EC = extracorporeal circulation; NS = not significant; ∗p < 0.05 versus previous time in placebo; +p < 0.05 versus previous time in PEG-rHuMGDF.) The Annals of Thoracic Surgery , DOI: ( /S (98) )
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Fig 3 White blood cell (WBC) count was increased 6 hours after extracorporeal circulation (EC) in both groups. However, WBC counts were comparable between the groups, suggesting polyethylene glycol derived recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) did not have any effect on the WBC population. (NS = not significant; ∗p < 0.05 versus previous time in placebo. +p < 0.05 versus previous time in PEG-rHuMGDF.) The Annals of Thoracic Surgery , DOI: ( /S (98) )
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Fig 4 The preoperative platelet count did not differ from predrug count in placebo or polyethylene glycol derived recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) groups. During 60 minutes of hypothermic extracorporeal circulation (EC), platelet count decreased to 10% of baseline and at 90 minutes platelet count during hypothermic EC recovered to 70% of baseline. Platelet count was comparable between the groups before and during EC. However, after EC, platelet counts were greater in the PEG-rHuMGDF group than in the placebo group. Within the first 6 hours after hypothermic EC, platelet count increased in drug-treated animals but was unchanged in the placebo group. In the placebo group at 72 hours after hypothermic EC, platelet count showed a second phase decrease while increasing progressively in the PEG-rHuMGDF group (∗p < 0.05 versus placebo.) The Annals of Thoracic Surgery , DOI: ( /S (98) )
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Fig 5 Platelet aggregation response to 10 μmol/L of adenosine diphosphate (the peak response) at each point. Extracorporeal circulation tended to impair platelet function at 1 hour postoperatively (Po), which recovered by the first Po day. There were no significant differences between groups after administration of drug or discontinuation of extracorporeal circulation. (PEG-rHuMGDF = polyethylene glycol derived recombinant human megakaryocyte growth and development factor, Pre Op = preoperative; ∗p < 0.05 between Po 1 h and Po 4 days in placebo.) The Annals of Thoracic Surgery , DOI: ( /S (98) )
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Fig 6 Platelet aggregation response to collagen. Polyethylene glycol derived recombinant human karyocyte growth and development factor (PEG-rHuMGDF) slightly enhanced platelet aggregation induced by collagen, 10 μg/mL, but there were no significant group differences at any time. (Po = postoperative; Pre Op = preoperative; ∗p < 0.05 between time points.) The Annals of Thoracic Surgery , DOI: ( /S (98) )
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