What causes extramedullary hematopoiesis (extramedullary blood cell production)?

From the Guidelines

Extramedullary hematopoiesis (EMH) is primarily caused by chronic hematologic disorders, such as myelofibrosis, polycythemia vera, and chronic myeloid leukemia, which lead to the formation of blood cells outside the bone marrow in organs like the liver, spleen, and lymph nodes. The condition occurs when the bone marrow is unable to produce sufficient blood cells, prompting the body to develop alternative sites for blood cell production 1. EMH can also result from bone marrow infiltration by malignancies or infections that disrupt normal hematopoiesis. Some key points about EMH include:

• The underlying mechanism involves hematopoietic stem cells migrating to and colonizing organs that had hematopoietic function during fetal development 1.
• This process represents a compensatory mechanism to maintain adequate blood cell production when the bone marrow is compromised.
• EMH can lead to organ enlargement, particularly hepatosplenomegaly, and may cause symptoms related to mass effect on surrounding structures, including abdominal discomfort, early satiety, and in severe cases, respiratory or neurological complications if EMH occurs in the thoracic cavity or spinal canal.
• The thoracic vertebral column is the most frequent site of nonhepatosplenic extramedullary hematopoiesis (EMH) in primary myelofibrosis (PMF), and other sites include lymph nodes, lung, pleura, small bowel, peritoneum, urogenital tract, and heart 1. Low-dose radiation therapy is currently the treatment of choice for PMF-associated nonhepatosplenic EMH, effectively treating symptomatic occurrences with 0.1 to 1 Gy in five to 10 fractions 1.

From the Research

Causes of Extramedullary Hematopoiesis

• Insufficient bone marrow function or ineffective erythropoiesis 2
• Chronic anemia 3
• Hematological disorders, such as malignancies 4
• Stromal disorders of the bone 4
• Infection, advanced tumors, anemia, and metabolic stress 5
• Ineffective hematopoiesis of the bone marrow 5

Associated Conditions

• Hematological disorders, including non-Hodgkin lymphoma 3
• Bone marrow examination showing insufficient hematopoietic function 6
• Clinical diagnosis of EMH, with variable mixture of bone marrow elements on fine-needle aspiration cytology (FNAC) 6

Pathophysiology

• Expansion and differentiation of hematopoietic stem and progenitor cells outside of the bone marrow 5
• Reactivation of the embryonic hematopoietic structure in organs 5
• Initiation of EMH by circulating hematopoietic stem cells trapped by chemokine (C-X-C motif) ligand 12 (CXCL12)-positive cells 4