Cellular and Molecular Effects of Hydroxycarbamide in Sickle Cell Patients

The increase in mean corpuscular volume (MCV) is the hematological parameter that better correlates with clinical improvement in sickle cell patients taking Hydroxycarbamide (HU). The mechanism by which HU increases erythrocyte MCV is still unclear. It could be due to megaloblastic changes in the bone marrow cells by the action of HU. To test our hypothesis, morphological, morphometric and cytometric analyses in bone marrow (BM) and peripheral blood (PB) cells of sickle cell patients were performed. Bone marrow smears showed signs of megaloblastic change, such as megaloblasts, red cells with open chromatin nuclei, hypersegmented neutrophils, giant metamyelocytes, and hypersegmented megakaryocytic nuclei. Morphometry showed a significant increase in cell surface area of blood cells in the HU group. In conclusion, we showed for the first time that HU causes megaloblastic change of the bone marrow cells of sickle cell patients and increases the MCV and the cell surface area, mechanisms that may reduce the polymerization of HbS molecules and the adhesive phenotype of sickle erythrocytes. This finding may shed light on the mechanisms of action of HU in sickle cell disease, helping in the search of new drugs and more personalized treatment for these patients.