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The bone marrow, one of the largest organs in the human body, accomplishes the enormous and complex task of blood cell production. In adults, the marrow produces 2.5 billion red cells, 2.5 billion platelets, and 1 billion granulocytes per kilogram of body weight on a daily basis. Blood cell production, which can increase up to 30-fold, depending upon increased peripheral demand or increased destruction, is mediated by complex interactions of marrow stem cells with stromal cells, hematopoietic growth factors, and interleukins. This chapter provides an overview of the developmental changes in hematopoiesis that occur from embryonic development through adolescence, addressing changes in the sites of hematopoiesis, components of peripheral blood, and the type of hemoglobin that is produced.


The anatomic sites of hematopoiesis change during the development of the embryo and fetus (Fig. 425-1). Red blood cell (RBC) formation first occurs within the yolk sac at 2 weeks’ gestation. In this primitive phase of hematopoiesis, clusters of cells called blood islands form in the yolk sac; the peripheral cells differentiate to become the walls of blood vessels, while the central cells become primitive red cells or hemocytoblasts. These primitive erythroblasts begin to enter the embryo proper at 21 to 22 days’ gestation, and circulate for approximately 12 weeks of gestation. A second wave of yolk-sac–derived definitive erythroid progenitors go to the liver at 5 weeks’ gestation. Hematopoietic progenitors are not seen in the yolk sac after 7 weeks’ gestation. Of note, yolk sac hematopoiesis is mainly of erythro-myeloid lineage.

Figure 425-1

Production of blood and hemoglobin (Hb) throughout development. Top: Changing sites of erythropoiesis throughout development. Red blood cell formation starts in the yolk sac in the embryo. Erythropoiesis then transitions to the liver and, to a lesser extent, the spleen during fetal life. The bone marrow is the sole normal site of erythropoiesis beginning shortly after birth and continuing throughout the remainder of life. Bottom: Simultaneous changes in globin production that occur as the site of blood formation changes. The main Hb of the fetus is Hb F (α2γ2). The predominant Hb after about 3 months of life is Hb A (α2β2).

Hematopoiesis continues mostly in the liver and to a lesser extent in the spleen between 7 to 15 weeks’ gestation. The liver continues as the main site of hematopoiesis through the fifth month of gestation and continues to produce blood cells through the first week of life (Fig. 425-1). The liver is the first site of definitive production of leukocyte precursors and platelet precursors (megakaryocytes), although erythroid elements are the predominant cell type.

Bone marrow hematopoiesis begins during the third and fourth months of gestation; it becomes the predominant site of hematopoiesis by the ...

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