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Abnormal Hemoglobins
Approach to Lymphocytosis
Nutrition and Blood
Systemic Mastocytosis
Erythropoiesis Stimulating
Pediatric hematology has emerged as a specialized science with age-speci c Medicines
reference ranges that correlate with the hematopoietic, immunologic and chemical Surgery and Hemostasis
changes in a developing child. A newborn represents the culmination of Pediatric Hematology
developmental events from conception and implantation through organogenesis. Amyloidosis
The embryo requires red cells for the transport of maternal oxygen to permit this New Oral Anticoagulants
growth and development. Birth brings dramatic changes in circulation and Antiphospholipid Syndrome
oxygenation, which affects hematopoiesis, as the newborn makes the transition to Castleman Disease
a separate biological existence. Clinical Trials
Common Hematology Tests
During embryogenesis, hematopoiesis occurs in distinct sites, including the Tumor Immunology
extraembryonic yolk sac, the fetal liver, and the preterm bone marrow. Bone Marrow Examination
Erythropoiesis is established soon after implantation of the blastocyst, with
primitive erythroid cells appearing in yolk sac blood islands by day 18 of gestation.

Hematopoietically active bone marrow is referred to as red marrow, as opposed to

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inactive yellow (fatty) marrow. At the time of birth, the bone marrow is fully active
and extremely cellular, with all hematopoietic cell lineages undergoing cellular Anemias
differentiation and ampli cation. In addition to the mature cells in fetal blood, Bleeding Disorders
there are signi cant numbers of circulating progenitor cells in cord blood. Blood Morphology
In a full-term infant, hepatic hematopoiesis has ceased except in widely scattered Blood Tests
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small foci that become inactive soon after birth. Postembryonic extramedullary
CD Markers
hematopoiesis is abnormal in a full-term infant. In a premature infant, foci of
Clinical Trials
hematopoiesis are frequently seen in the liver and occasionally observed in the
Cutaneous Lymphomas
spleen, lymph to
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Disorders of the red cell
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Dramatic changes occur in the blood and bone marrow of the newborn infant Drugs
during the rst hours and days after birth and there are rapid uctuations in the Hematologic Emergencies
quantities of all hematologic elements. The values of most of the hematological Hemoglobinopathies
parameters studied were highest especially hemoglobin concentration, packed cell Hemostasis
volume, reticulocyte count and red cell indices on the rst day of life and thereafter Immune System
declined. Factors contributing to the decline in hematological parameters in the Infections
newborn are due to decrease in blood erythropoietin concentration soon after Introduction to Hematology
birth, reducing the erythropoietic rate. Also, transient hemolysis is high during the Iron Disorders
Leukemias
rst days or week after birth. Signi cant hematologic differences are seen
Lymphomas
between term and preterm infants and among newborns, infants, young children,
Miscellaneous Leukocyte
and older children.
Abnormalities
Neonatal hematologic values are affected by the gestational age of the infant, the Miscellaneous Red Cell
age in hours after delivery, the presence of illness, and the level of support Abnormalities
required. Other important variables to be considered when evaluating laboratory Myelodysplastic Syndromes
data include the site of sampling and technique (capillary versus venous puncture, Myeloproliferative Disorders
warm or unwarmed extremity), the timing of sampling, and conditions such as the Nutrition
course of labor and the treatment of the umbilical vessels. The presence of fetal Paraneoplastic Syndromes
hemoglobin (Hb F), bilirubin, and lipids in newborns can also interfere with Pediatric Hematology
hematology laboratory testing. As with all laboratory testing, each laboratory Plasma Cell Disorders
should establish reference intervals based on its instrumentation, methods, and Platelet Disorders
Procedures
patient population.
Radiology
The concentration of hemoglobin uctuates dramatically in the weeks and months Red Cell Enzyme Defects
after birth as a result of physiologic changes, and various factors must be Sickle cell disease (HbS)
considered when analyzing pediatric hematologic values. The site of sampling, Spleen Disorders
gestational age, and the time interval between delivery and clamping of the Stem Cell Transplantation
umbilical cord can in uence the hemoglobin level in newborn infants. In addition, Thalassemias
there are signi cant differences between capillary and venous blood hemoglobin Thrombotic Disorders
levels. Capillary samples in newborns generally have a higher hemoglobin Transfusion Medicine
concentration than venous samples, which can be attributed to circulatory factors. Transfusion Reactions
Racial differences must also be considered when evaluating hemoglobin levels in
children. African American children have hemoglobin levels averaging 0.5 g/dL Archives
lower than those in white children.
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Normal Hemoglobin Values in Infants
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Hemoglobin synthesis results from an orderly evolution of a series of embryonic,
June 2018
fetal, and adult hemoglobins. At birth, Hb F constitutes 70% to 80% of the total
May 2018
hemoglobin. Hb F declines from 90% to 95% at 30 weeks’ gestation to
April 2018
approximately 7% at 12 weeks after birth and stabilizes at 3.2 ± 2.1% at 16 to 20
March 2018
weeks after birth. The switch from Hb F to Hb A is genetically controlled and
February 2018
determined by gestational age; it does not appear to be in uenced by the age at
January 2018
which birth occurs. December 2017
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Early normoblasts are megaloblastic, hypochromic, and irregularly shaped. During
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hepatic hematopoiesis, normoblasts are smaller than the megaloblasts of the yolk October 2017 
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sac but are still macrocytic. Erythrocytes remain macrocytic from the rst 11 September 2017
weeks of gestation until day 5 of postnatal life. August 2017
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Peripheral blood lm for a normal newborn demonstrating a normal March 2016
lymphocyte, macrocytes, polychromasia, and one nucleated red blood cell February 2016
(×1000).

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The macrocytic RBC morphology gradually changes to the characteristic
normocytic, normochromic morphology. Orthochromic normoblasts frequently are
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observed in the full-term infant on the rst day of life but disappear within
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postnatal days 3 to 5. These nucleated RBCs (NRBCs) may persist longer than a
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week in immature infants. The average number of NRBCs ranges from 3 to 10 per
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100 white blood cells (WBCs) in a normal full-term infant to 25 NRBCs per 100
WBCs in a premature infant. The presence of NRBCs for more than 5 days
suggests hemolysis, hypoxic stress, or acute infection.

Peripheral blood lm for a premature infant showing a normal lymphocyte,

four nucleated red blood cells, and increased polychromasia (×500).

The erythrocytes of newborns show additional morphologic differences. The

number of biconcave discs relative to stomatocytes is reduced in neonates (43%
discs, 40% stomatocytes) compared with adults (78% discs, 18% stomatocytes).
In addition, increased numbers of pitted cells, echinocytes, spherocytes, and other
abnormally shaped erythrocytes are seen in neonates. The number of these
“dysmorphic” cells is even higher in premature infants. Zipursky et al found 40%
discs, 30% stomatocytes, and 27% additional poikilocytes in premature infants.

Apparent reticulocytosis exists during gestation, decreasing from 90%

reticulocytes at 12 weeks’ gestation, to 15% at 6 months’ gestation, and
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ultimately to 4% to 6% at birth. Reticulocytosis persists for about 3 days after
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birth, then declines abruptly to 0.8% reticulocytes on postnatal day 4 to 7. At 2
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months, the number of reticulocytes increases slightly, followed by a slight decline

from 3 months to 2 years, when adult levels of 0.5% to 1.5% are attained. The
reticulocyte count of premature infants is typically higher than that of term infants;
however, the count can vary dramatically depending upon how ill the newborn is.
Signi cant polychromasia seen on a Wright-stained blood lm is indicative of
postnatal reticulocytosis

In summary, hemopoiesis mainly occurs in the liver of the fetus. After birth and
throughout life, hemopoiesis occurs in the bone marrow. In infants and the
growing child, this occurs in all bones of the skeleton. An understanding of the
normal cytology is essential in order to allow for the identi cation of abnormalities
on the blood lm. Red cells are the most numerous cell type encountered in the
blood lm. In the pediatric lm, normal red cells are the size of the lymphocyte
nucleus with a diameter of 7–9µm and a mean corpuscular volume (MCV) of 75–
90 fL. They should be round in shape with a smooth contour appearing as a
biconcave disc. Approximately, one-third of the cell should have a central pallor.
The neonatal blood lm differs from the pediatric blood lm. It is not uncommon to
see burr cells (echinocytes), occasional nucleated red blood cells (RBC), target
cells, fragmented red cells, and some spherocytes. Neonates typically have an
elevated MCV and red cells are therefore macrocytic. Nucleated red cells or
normoblasts are immature red cells with a retained nucleus. They are usually
found only in the circulating blood of the fetus and the newborn infant. Post
infancy, their presence in the peripheral blood is indicative of disorder in blood
production. Nucleated red blood cells are immature cells, they do not enter the
peripheral blood under normal circumstance. They are often seen in the peripheral
blood in leukoerythroblastic anemia, hemolysis, hypoxia, and marrow in ltration.

White blood cells can be divided into the myeloid/monocytic cells (neutrophils,
eosinophils, basophils, and monocytes) and lymphocytes. Segmented neutrophils
are the predominant white cells in the peripheral blood. The total white cell count
and the neutrophil, monocyte and lymphocyte counts are often much higher in the
neonate than the older child. In addition, it is important to remember that the
automated lymphocyte count may be
falsely elevated due to the presence of nucleated red blood cells.

Healthy newborn infants may have a WBC count from 13,000 to 38,000 per
mm3 (13.0 to 38.0 × 109 per L) at 12 hours of life. By two weeks of age, this
decreases to approximately 5,000 to 20,000 per mm3 (5.0 to 20.0 × 109 per L),
and gradually declines throughout childhood to reach adult levels of 4,500 to
11,000 per mm3 (4.5 to 11.0 × 109 per L) by about 21 years of age. There is also a
shift from relative lymphocyte to neutrophil predominance from early childhood to
the teenage years and adulthood.

White Blood Cell Count Variation with Age

Platelets are small, non-nucleated cells. They normally measure 1.5–3 µm in

diameter. They are derived from the cytoplasmic fragments of
megakaryocytes. The platelet count usually ranges from 150 to 400 × 109/L for
full-term and preterm infants, comparable to adult values. Platelet counts
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generally increase in both term and preterm infants in the rst few months of life,
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as evidenced by increased mean platelet volume in the rst month of life.
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Thrombocytopenia of fewer than 100 × 109 platelets/L may be seen in high-risk

infants with sepsis or respiratory distress and neonates with trisomy syndromes,
and investigation should be undertaken for underlying pathology. Platelets of a
newborn infant show great variation in size and shape.

The physiology of the hemostatic system in infants and children is different from
that in adults. The vitamin K–dependent coagulation factors (factors II, VII, IX, and
X) are at about 30% of adult values at birth; they reach adult values after 2 to 6
months, although the mean values remain lower in children than in adults. Levels
of factor XI, factor XII, prekallikrein, and high-molecular-weight kininogen are
between 35% and 55% of adult values at birth, reaching adult values after 4 to 6
months. In contrast, the levels of brinogen, factor VIII, and von Willebrand factor
are similar to adult values throughout childhood. Factor V decreases during
childhood, with lower levels during the teen years as compared with adults. The
physiologic anticoagulants and inhibitors of coagulation—protein C, protein S,
antithrombin, and a disintegrin-like and metalloprotease domain with
thrombospondin type 1 motifs 13 (ADAMTS 13)—are reduced to about 30% to
40% at birth. Antithrombin reaches adult values by 3 months, whereas protein C
does not normalize until after 6 months. In the brinolytic system, levels of
plasminogen and α2-antiplasmin are similar to adult levels at birth, whereas
levels of tissue plasminogen activator are low and levels of plasminogen activator
inhibitor (PAI) are increased. The hemostatic components are not only changing in
concentration over the rst few weeks to months of life, but their values are also
dependent upon the gestational age of the child, and premature infants have
different values at birth than term infants.

References:
Esan AJ. Hematological differences in newborn and aging: a review study.
Hematol Transfus Int J. 2016;3(3):178-190. https://medcraveonline.com/HTIJ/HTIJ-
03-00067.php

Linda H. Goossen. Pediatric and Geriatric Hematology

https://oncohemakey.com/pediatric-and-geriatric-hematology/

McNaughten B, Thompson A, Macartney C, et al. Arch Dis Child Educ Pract Ed

2018;103:263–266. https://ep.bmj.com/content/edpract/103/5/263.full.pdf

LYRAD K. RILEY, MD, and JEDDA RUPERT, MD. Evaluation of Patients with
Leukocytosis. https://www.aafp.org/afp/2015/1201/p1004.html

Adewoyin AS, Nwogoh B. Peripheral blood lm – a review. Ann Ib Postgrad Med

2014;12:71–9.

Gordon-Smith T. Haemopoiesis – the formation of blood cells. Medicine

2009;37:129–32.

Hays T, Jamieson B. Atlas of paediatric peripheral blood smears. 1st edn: Abbott
Laboratories, 2008.

Bain BJ, Bates I, Laffan MA. Dacie and Lewis practical haematology: Elsevier
Health Sciences, 2016.

Bain BJ. Blood cells: a practical guide: John Wiley & Sons, 2015.

Summary

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Article Name

Pediatric Hematology

Description

Pediatric hematology has emerged as a specialized

science with age-speci c reference ranges that correlate
with the hematopoietic, immunologic and chemical
changes in a developing child.

Author

Dr Moustafa Abdou

Publisher Name

askhematologist.com

Publisher Logo

Dr Moustafa Abdou

Category: Pediatric Hematology

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