Embryonic hemoglobins are produced during yolk sacerythropoiesis, then replaced by fetal hemoglobin (hemoglobin F, α2γ2) during the hepatic phase. During the thirdtrimester, gamma chain production gradually diminishes,replaced by beta chains, resulting in hemoglobin A (a2β2). Some fetal factors (e.g., infant of a diabetic mother) delayonset of beta chain production, but premature birth doesnot. Just after birth, with rapid increases in oxygen saturation, erythropoietin production stops and, thus, erythropoiesis ceases. Fetal RBCs have a shorter survival time (60days).
During the first few months of postnatal life, rapid growth, shortened RBC survival, and cessation of erythropoiesis cause a gradual decline in hemoglobin levels, with a nadir at 8 to 10 weeks of life. This so-called physiologic nadir is accentuated in premature infants. Erythropoietin is produced in response to the decline in hemoglobin and decreased oxygen delivery. Erythropoiesis subsequently resumes with an increase in the reticulocyte count. The hemoglobin level gradually increases, accompanied by synthesis of increasing amounts of hemoglobin A. By 6 months of age in healthy infants, only trace gamma chain synthesis occurs.
Production of neutrophil precursors is controlled predominantly by two different colony-stimulating factors (seeFig. 149-1). The most immature neutrophil precursors arecontrolled by granulocyte-macrophage colony-stimulating factor (GM-CSF), produced by monocytes and lymphocytes. GM-CSF increases the entry of primitive precursorcells into the myeloid line of differentiation. Granulocyte colony-stimulating factor (G-CSF) augments the production of more mature granulocyte precursors. GM-CSF and G-CSF, working in concert, can augment production of neutrophils, shorten the usual 10to 14-day production timefrom stem cell to mature neutrophil, and stimulate functional activity. The rapid increase in neutrophil count thatoccurs with infection is caused by release of stored neutrophils from the bone marrow, under the control of GM-CSF.During maturation, a mitotic pool of neutrophil precursorsexists—myeloblasts, promyelocytes, and myelocytes possessing primary granules. The postmitotic pool consists ofmetamyelocytes, bands, and mature polymorphonuclear leukocytes containing secondary or specific granules thatdefine the cell type. Only bands and mature neutrophils arefully functional with regard to phagocytosis, chemotaxis,and bacterial killing. Neutrophils migrate from the bonemarrow, circulate for 6 to 7 hours, and enter the tissues, where they become end-stage cells that do not recirculate.Eosinophil production is under the control of a related glycoprotein hormone, interleukin 3. Eosinophils, which playa role in host defense against parasites, also are capable ofliving in tissues for prolonged periods.
Megakaryocytes are giant, multinucleated cells derivedfrom the primitive stem cell and are polyploid (16 to 32 timesthe normal DNA content) because of nuclear but not cytoplasmic cell division. Platelets form by invagination of themegakaryocytic cell membrane and bud off from the periphery. Thrombopoietin is the primary regulator of plateletproduction. Platelets adhere to damaged endothelium andsubendothelial surfaces via specific receptors for the adhesive proteins, von Willebrand factor (vWF), and fibrinogen.Platelets also have specific granules that readily release theircontents after stimulation and trigger the process of plateletaggregation. Platelets circulate for 7 to 10 days and have nonucleus.