G-CSF administration results in thrombocytopenia by inhibiting the differentiation of hematopoietic progenitors into megakaryocytes.

Hematopoietic stem cell transplantation (HSCT) plays an important role in the therapy of hematological malignancies and some nonmalignant diseases. Granulocyte colony-stimulating factor (G-CSF) is generally used to mobilize and collect hematopoietic stem cells from donors and accelerate neutrophil recovery in transplantation recipients. However, less attention has been paid to the fact that G-CSF administration might result in thrombocytopenia and enhance bleeding risk in HSCT. In this study, we investigated the effects of G-CSF on platelet counts in healthy mice and mice that received bone marrow transplantation. It was observed that G-CSF administration induced thrombocytopenia in healthy mice and aggravated thrombocytopenia in mice that received bone marrow transplantation. Furthermore, we analyzed the regulatory effects of G-CSF on the differentiation of hematopoietic progenitors and megakaryocytes, and activation of platelets and endothelial cells. The results reveal that G-CSF administration causes thrombocytopenia mainly by inhibiting the differentiation of common myeloid progenitors and megakaryotic erythroid progenitors into megakaryocytes and platelet formation but not through enhancing activation of platelets or endothelial cells and following platelet consumption. Collectively, G-CSF administration can result in thrombocytopenia in hematopoietic stem cell donors and exacerbate existing thrombocytopenia in transplantation recipients. More attention should be paid to bleeding risk of G-CSF administration in HSCT, especially autologous HSCT.