(A) In polycythemia vera, erythropoietin-independent JAK-STAT activation results in increased erythroferrone production to support iron availability for enhanced erythropoiesis. There is also basally increased hypoxia inducible factor (HIF). (B) Iron restriction in polycythemia vera biases the pre-megakaryocytic/erythroid progenitor toward megakaryopoiesis, reducing hemoglobin/hematocrit and increasing platelet count. Reduced cellular iron induced by phlebotomy decreases PHDs, which are the primary negative regulators of HIFs, resulting in further augmentation of HIF activity. Created with BioRender.com.