Extramedullary Hematopoiesis (EMH)

Extramedullary hematopoiesis (EMH) refers to the formation and development of blood cells outside the medulla of the bone (bone marrow). This process can be either physiologic or pathologic. Physiologic EMH occurs during embryonic and fetal development in sites like the liver, spleen, yolk sac, aorta–gonad mesonephros region, and lymph nodes. Pathological EMH occurs in children or adults when bone marrow function is impaired or insufficient, common causes including myelofibrosis, thalassemias, chronic anemia, advanced tumors, metabolic stress, and infections. It acts as a compensatory mechanism for ineffective hematopoiesis in the bone marrow and most frequently occurs in the spleen and liver, but can also occur in skin, lungs, kidneys, or other organs. The process involves expansion and differentiation of hematopoietic stem and progenitor cells (HSPCs) outside of bone marrow, and the extramedullary microenvironment supports proliferation through cytokine signaling. Clinical manifestations include enlarged spleen (splenomegaly) and liver (hepatomegaly), and skin nodules. Complications may arise from mass effect or organ dysfunction. EMH is regulated by growth factors, transcription factors, and cytokines, and involves interactions between migrating HSCs/HSPCs and supportive microenvironmental cues.