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• Mesoblastic hematopoiesis


  Occurs in the yolk sac, begins between 10th -14th days of gestation, ceased by 10–12 weeks
• Hepatic hematopoiesis


  Starts at 6–8 weeks of gestation, the predominant hematopoietic organ through weeks 20–24 of gestation
• Myeloid hematopoiesis


  Begins in 2nd trimester & continues throughout life
• Production of all hematopoietic tissues

  1. Begins with pluripotent stem cells that are capable of both self-renewal and clonal maturation into all blood cell lineages

  2. Progenitor cells differentiate under the influence of hematopoietic growth factors produced by the fetus

  
• Term hematocrits


  • Range from 50–63%
• MCV


  • Inversely proportional to gestation and to the life span of the cell
  • Embryo >180 fL
  • Midgestation -130 fL
  • Term -110 fL
• Platelet concentrations


  • Remain constant from 18 weeks of gestation through term, with a range of 150,000–450,000/μL
• MPV


  • 8–10 fL at birth, helpful in determining whether diminished platelet counts are caused primarily by decreased production (normal MPV) or increased destruction (large MPV)
• Erythropoiesis in utero


  Controlled by erythroid growth factors produced solely by the fetus
• Erythropoietin (EPO) does not cross the placenta in humans
• Regulation of EPO gene expression

  Involves an oxygen-sensing mechanism, and both hypoxia and anemia stimulate erythropoiesis by stimulating mRNA transcription and EPO production
• Fetal liver


  Produces EPO during the first and second trimesters
• After birth


  The site of EPO production shifts from the liver to the kidney
• In animal models, the sensitivity of the hepatic hypoxia-sensing mechanism appears decreased compared with renal sensitivity postnatally
• EPO-stimulates precursors


  Colony-forming units-erythroid (CFU-E) in bone marrow clonally mature into clusters containing 30–100 normoblasts-erytrocytes
• Hemoglobin


  A complex protein consisting of iron-containing heme groups and the protein moiety globin, with a dynamic interaction between heme and globin giving it unique properties in the reversible transport of oxygen
• Hemoglobin molecule


  A tetramer made up of two pairs of polypeptide chains, with each chain having a heme group attached
• Fetal hemoglobin (HbF)


  Made up of two alpha and two gamma globin chains, represented as α2γ2
• Adult hemoglobin (Hb A)

  Made up of one pair of alpha (α) and one pair of beta (β) polypeptide chains, represented as α2β2
• Fetal Hemoglobin (HbF)


  Contains γ polypeptide chains in place of the β chains of Hb A, its resistance to denaturation by strong alkali is the basis for determining the presence of fetal RBCs in the maternal circulation (the Kleihauer-Betke test)<|>After the 8th gestational week, Hb F is the predominant hemoglobin; at 24 weeks gestation it constitutes 90% of the total hemoglobin<|>During the 3rd trimester, a gradual decline occurs, so that at birth Hb F averages 70% of the total
• Anemia


  Any value for the hemoglobin or hematocrit that is 2 SDs below the mean for age and sex
• Anemia with "normal range" hemoglobin level can occur in cyanotic cardiac or pulmonary disease
• Anemia is often not a disease per se, but rather a manifestation of some other primary process
• Types of anemias


  • Hypochromic, microcytic anemia
  • Normocytic anemias
  • Macrocytic anemia
• Hypochromic, microcytic anemia


  Caused by an inadequate production of hemoglobin, e.g. iron deficiency and thalassemia
• Normocytic anemias


  Associated with a systemic illness that impairs adequate marrow synthesis of RBCs
• Macrocytic anemia


  Caused by vitamin B12 and folic acid deficiencies
• Hemolytic diseases


  • Intrinsic RBC disorders (hereditary spherocytosis, hereditary elliptocytosis, RBC enzyme deficiencies)
  • Disorders extrinsic to the RBC (immune-mediated hemolysis, extravascular and intravascular)
• Hypoproliferative anemias


  Anemias associated with normocytic and normochromic red cells and an inappropriately low reticulocyte response (reticulocyte index <2.0–2.5), e.g. early iron deficiency, acute and chronic inflammation, renal disease, hypometabolic states
• Physiologic Anemia of Infancy

  Progressive decline in hemoglobin level begins and persists for 6–8 weeks, due to increased oxygen availability, developmental switch from fetal to adult hemoglobin, and downregulation of EPO production
• Physiologic anemia in premature infants

  More extreme and rapid decline, due to short survival of RBCs, rapid RBC mass expansion, inadequate EPO synthesis, and blunted EPO response
• Physiologic anemia requires no therapy other than folic acid and iron
• Iron balance


  The majority of iron (75%) is bound in heme proteins (hemoglobin and myoglobin), the remainder is bound in storage proteins or critical enzyme systems, and most iron is recycled from the breakdown of old red blood cells
• The body must protect itself from free iron, which is highly toxic as it participates in chemical reactions that generate free radicals
• Iron-Deficiency Anemia


  Anemia resulting from lack of sufficient iron for synthesis of hemoglobin, the most common hematologic disease of infancy and childhood
• 30% of the global population suffers from iron-deficiency anemia
• In the United States, about 9% of toddlers & adolescent girls are iron deficient; 3% & 2 % respectively have iron deficiency anemia
• In some developing countries, up to 50 percent of preschool children and pregnant mothers have anemia that principally is caused by iron deficiency
• Newborn infant iron content

  About 0.5 g, whereas the adult content is 5 g, requiring an average of 0.8 mg of iron to be absorbed each day during the first 15 years of life
• Dietary iron absorption


  Assumed to be about 10%, requiring a diet containing 8–10 mg of iron daily for optimal nutrition<|>Iron is absorbed 2 to 3 times more efficiently from human milk than from cow's milk