Sites of Haematopoiesis

Normal Haematopoiesis

The bone marrow is the only site of blood production in extrauterine life. The yolk sac and the liver produce blood in the intrauterine life. The two sites have distinct precursors. The yolk sac haematopoiesis, known as primitive haematopoiesis, is transient haematopoiesis that serves the purpose of rapidly providing blood to the growing embryo. Haematopoietis in the liver in utero and subsequently extrauterine haematopoiesis in the bone marrow are known as definitive haematopoiesis. The haemopoietic precursors of primitive haematopoesis disappear once the definitive haematopoiesis establishes.

The first evidence of haematopoiesis in the developing embryo is in the yolk sac. Yolk sac erythropoiesis produced nucleated erythrocytes and macrophages but no granulocytes. The yolk sac erythrocytes are large, nucleated and have embryonic haemoglobins. The yolk sac remains the site for erythropoieis from 19 days to 8 weeks of intrauterine life. The yolk sac haematopoiesis ceases once the liver becomes the dominant site of haematopoiesis.

Liver is the main site for erythropoiesis through intrauterine life. Haematopoiesis taking place in the liver differs from the yolk sac haematopoiesis in the following ways

1. Liver haematopoiesis produced erythrocytes, moncytes and lymphocytes, yolk sac only produces erythrocytes and monocytes
2. Erythrocytes produced by the liver are smaller
3. The erythrocytes enucleate before release into blood. Yolk sac erythrocytes are released with a nucleus that enucleates in circulation.
4. The erythrocytes have have fetal haemoglobin whereas the yolk sac erythrocytes have embryonic haemoglobin.

The precursors involved in definitive haematopoiesis originate in the mesodermal tissue of the the aorta-gonad-mesonephros region and migrate to the liver from there (The Lancet 2013; 381:S12). From the liver, haemopoietic progenitors migrate the bone marrow. The contribution of the bone marrow increases with gestational age and the bone marrow becomes the only site for normal haematopoiesis in the extrauterine life.

Haematopoiesis sites in disease 

Haematopoiesis can take place in the liver, spleen, lymph node, kidney and posterior mediastinum when the bone marrow function is insufficient. Rarely, involvement of other organs including adrenal gland, central nervous system, skin and spine have been described. Extramedullary erythropoiesis is seen where bone marrow is diseased or overwhelmed.

1. Diseased bone marrow: Bone marrow diseases like myelofibrosis and bone marrow infiltrations limit the marrow available for haematopoiesis forcing haematopoiesis to extramedullary sites.
2. Overwhelmed bone marrow: Patients with chronic haemolytic anaemia and thalassaemias have bone marrow expansion to cope up with increased demand of erythrocytes. Extramedullary erythropoiesis may be seen in patients whose needs are not met with full marrow expansion.

Extramedullary haematopoiesis can cause symptoms including

1. Leukoerythroblastic anaemia and the presence of tear drop erythrocytes.
2. Symptoms caused by splenomegaly:
3. Spinal cord compression (usually thoracic)
4. Rare manifestation include effusion due to involvement of the serious membranes and compression by masses arising from the skull and the paranasal sinuses