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CHAPTER 7 less than 2 to 3 percent of the total hemoglobin by 6 months of age. The mean

HEMATOLOGY OF THE FETUS hemoglobin level in cord blood at term is 16.8 g/dL, with 95 percent of the
values falling between 13.7 and 20.1 g/dL. The red cells of the newborn are
AND NEWBORN macrocytic, with a mean cell volume in excess of 110 fL/cell. The red cell, hemo-
globin, and hematocrit values decrease only slightly during the first week after
birth, but decline more rapidly in the following 5 to 8 weeks, producing the
physiologic anemia of the newborn. The absolute number of neutrophils in the
James Palis and George B. Segel blood of term and premature infants is usually greater than that found in older
children. Segmented neutrophils are the predominant leukocytes in the first
few days after birth. As their number decreases, the lymphocyte becomes the
SUMMARY most numerous cell type and remains so during the first 4 years of life. Phago-
cytosis of bacteria by neutrophils from premature and term infants is normal.
During embryogenesis, hematopoiesis occurs in spatially and temporally Bactericidal activity varies according to the conditions of testing and the clin-
distinct sites, including the extraembryonic yolk sac, the fetal liver, and the ical status of the neonates. The platelet counts in term and preterm infants
preterm marrow. The development of primitive erythroblasts in the yolk sac are between 150 and 400 × 10 /L, comparable to adult values. The absolute
9
is critical for embryonic survival. Primitive erythroblasts differentiate within number of lymphocytes in the newborn is equivalent to that in older children,
the vascular network rather than in the extravascular space and circulate as with lower values in premature infants at birth. The absolute number of CD3+
nucleated cells. Although it is widely assumed that primitive red cells remain and CD4+ (helper/inducer phenotype) T-cell subsets in blood of newborns is
nucleated throughout their life span, primitive erythroblasts ultimately enu- significantly higher than in adults. Humoral (B-cell) immunity also develops
cleate upon terminal differentiation. After 7 weeks of gestation, hematopoi- early in gestation, but it is not fully active until after birth. In the newborn,
etic progenitors are no longer detected in the yolk sac. Hematopoietic stem approximately 15 percent of lymphocytes have immunoglobulin on their sur-
cells emerge from major arterial vessels at 5 weeks of gestation. The liver face, with all immunoglobulin isotypes represented. The term newborn has
serves as the primary source of red cells from the 9th to the 24th week of ges- reduced mean plasma levels (<60 percent of adult levels) of factors II, IX, X,
tation. Like primitive erythropoiesis in the yolk sac, definitive erythropoiesis XI, and XII, prekallikrein, and high-molecular-weight kininogen. In contrast,
in the fetal liver is necessary for continued survival of the embryo. In contrast the plasma concentration of factor VIII is similar and von Willebrand factor is
to the yolk sac, where hematopoiesis is restricted to maturing primitive ery- increased compared to older children and adults.
throid, macrophage, and megakaryocytic cells, hematopoiesis in the fetal
liver consists of definitive erythroid, megakaryocyte, and multiple myeloid, as
well as lymphoid lineages. Hematopoietic cells are first seen in the marrow
of the 10- to 11-week embryo, and they remain confined to the diaphyseal FETAL HEMATOLYMPHOPOIESIS
regions of long bones until 15 weeks of gestation. Lymphopoiesis is present
in the lymph plexuses and the thymus beginning at 9 weeks of gestation. Yolk PRODUCTION OF EMBRYONIC AND FETAL
sac stem cells were first thought to seed the liver and eventually the marrow. HEMATOPOIETIC CELLS
However, later experiments in avian and amphibian embryos indicate that the During embryogenesis, hematopoiesis occurs in spatially and tempo-
hematopoietic stem cells that seed the marrow arise within the body of the rally distinct sites, including the extraembryonic yolk sac, the fetal liver,
embryo proper rather than from the yolk sac. The aorta-gonad-mesonephros the thymus, and the preterm marrow. The origin of hematopoietic cells
(AGM) region generates hematopoietic stem cells that seed the liver and the is closely tied to gastrulation, the formation of mesoderm cells, and to
marrow to provide lifelong hematopoiesis. Hemoglobin (Hgb) Gower-1 (ζ ε ) the emergence of the endothelial lineage. Hematopoiesis is first estab-
2 2
is the major hemoglobin in embryos younger than 5 weeks. Hgb F (α γ ) is the lished soon after implantation of the blastocyst, with the appearance of
2 2
major hemoglobin of fetal life. The fetal hemoglobin concentration in blood primitive erythroid cells in blood islands of the yolk sac beginning at
1
decreases after birth by approximately 3 percent per week and is generally day 18 of gestation. The spatial and temporal association of embryonic
red cells and endothelial cells in these blood islands suggests that the
transient erythromyeloid potential of the yolk sac arises from heman-
gioblast precursors that also contain endothelial potential. This concept
2
is supported by in vitro studies of human embryonic stem cells cultured
as embryoid bodies. Hematopoietic stem cells, containing erythromy-
3,4
Acronyms and Abbreviations: ADP, adenosine diphosphate; AGM, aorta- eloid and lymphoid potential, subsequently arise from intraembryonic
gonad-mesonephros; ATP, adenosine triphosphate; ATPase, adenosine triphos- vasculature, particularly the aorta (Fig. 7–1). These hematopoietic stem
phatase; BFU-E, burst-forming unit–erythroid; BPG, bisphosphoglycerate; BPI, cells provide for fetal and long-term postnatal blood cell production.
bacterial permeability-increasing protein; cAMP, cyclic adenosine monophosphate; The ontogeny of the hematopoietic system remains a topic of active
CFU-E, colony-forming unit–erythroid; CFU-GEMM, colony-forming unit–granu- research using mammalian and several nonmammalian model systems.
locyte-erythroid-monocyte-macrophage; CFU-GM, colony-forming unit–granulo-
cyte-monocyte; CFU-Meg, colony-forming unit–megakaryocyte; G-CSF, granulocyte Yolk Sac Hematopoiesis
colony-stimulating factor; GM-CSF, granulocyte-monocyte colony-stimulating fac- “Primitive” red cells derived from the yolk sac constitute a distinct
tor; IL, interleukin; MCV, mean cell volume; NBT, nitroblue tetrazolium; NK, natural transient erythroid lineage that differs from “definitive” red cells that
killer; RDW, red cell distribution width; SIDS, sudden infant death syndrome; TNF, subsequently mature in the fetal liver and marrow. The development of
tumor necrosis factor; TPO, thrombopoietin. primitive erythroblasts is critical for embryonic survival. In the mouse,
targeted disruption of the transcription factors SCL (TAL1), LM02

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