Transient thrombocytopenia produced by administration of macrophage colony-stimulating factor: Investigations of the mechanism

Administration of macrophage colony-stimulating factor (M-CSF) to mice (2 to 8 mg/kg/d x 5d) produced dose-dependent thrombocytopenia, which reached its nadir on days 4 to 5, followed by rapid recovery. Surprisingly, when administration of M-CSF was prolonged, the thrombocytopenia completely resolved, despite continued treatment, Splenectomy did not prevent the thrombocytopenia. Readministration of M-CSF after various intervals continued to produce the thrombocytopenic effect, even after 35 days. Measurements of Meg-CFC and megakaryocyte ploidy during the periods of M-CSF treatment and recovery of normal platelet levels showed no evidence of bone marrow suppression, Platelet survival was markedly decreased after 5 days of M-CSF (at the platelet count nadir) and after 9 days of continued M-CSF treatment, when the platelet count had returned to normal. Platelets from M-CSF-treated donors demonstrated normal survival when transfused into normal recipients. We concluded that thrombocytopenia produced by M-CSF was not due to suppression of thrombopoiesis, but to increased activity of the monocyte/macrophage system. which caused shortened platelet survival, and that subsequently, increased platelet production compensated for ongoing platelet destruction and resulted in normal platelet levels. (C) 1998 by The American Society of Hematology.