EPO and Splenomegaly: In the context of EPO-induced splenomegaly in murine models, the enlargement of the spleen may be attributed to several interrelated processes, including increased splenic function (e.g., extramedullary hematopoiesis), abnormal blood flow (e.g., portal hypertension), accumulation of abnormal proteins or lipids, and infiltration of benign or malignant cells (18–20).