Neonatal and geriatric assessment of hematological parameters

ABSTRACT

OBJECTIVE: This work aims at highlighting
the hematological variables of these groups (neonates and
elderly) and call for the hematological values at all the
different stages of these groups.

METHOD: Consultation of different
scientific presentation were made and relevant information were
retrieved.

CONCLUSION: Hematological changes are
obvious in both the neonates and the elderly persons and at such,
different hematological variables must be implemented in various
developing stages of the neonates as well as the different
classes of aged elderly individuals. Also among the elderly,
certain hematological disorders are more dominants and clinicians
should be attentive to this.

KEYWORDS: Hematology, Parameters, Neonates,
Elderly

Corresponding Author: Peter Ubah
Okeke

Student, School of Science &
Engineering,

Atlantic International University,
Honolulu- Hawaii

www.aiu.edu

Term paper

INTRODUCTION TO
NEONATAL HEMATOPOIESIS

The newborn infant, older child and adults
all exhibit profound hematologic differences. Because children
mature at different rates, it is inappropriate to use adult
reference ranges for the assessment of pediatric blood values.
Pediatric hematology has emerged as a specialized science with
age- specific reference ranges that correlate the hematopoietic,
immunologic and chemical changes of a developing
child.

Hematopoiesis, the formation and
development of blood cells from stem cells begins in the first
weeks of embryonic development and proceeds systematically
through three phases of development; Mesoblastic (yolk sac),
Hepatic ( liver), and myeloid (bone marrow). The cells produced
in the developing embryo are primitive erythroblasts formed in
the yolk sac. These cells are particularly interesting because
they do not develop into mature erythrocytes. They are
erythropoietin insensitive and have the ability to differentiate
into other cell lines on exposure to appropriate growth factors
Christensen R D (1989).

By the second month of gestation,
hematopoiesis ceases in the yolk sac and the liver becomes the
centre for hematopoiesis, reaching its peak activity during the
third and fourth gestational months. Leukocytes of each cell type
systematically make their appearance. In week 9 of gestation,
lymphocytes can be detected in the region of the thymus. They are
subsequently found in the spleen and lymph nodes. During the
fourth and fifth gestational months, the bone marrow emerges as
major site of blood cell production and it becomes the major site
by birth Forestier F et al (1995).

Hematopoietically active bone marrow is
referred to as red marrow, as opposed to 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 differentiation and amplification. In
addition to the mature cells in fetal blood, there are
significant numbers of circulating progenitor cells in cord blood
Linch et al (1982)

In a full term infant, hepatic
hematopoiesis has ceased except in widely scattered small foci
that become inactive soon after birth Hann et al (1983).
Postembryonic extramedullary hematopoiesis is abnormal in a full
term infant. In a premature infant, foci of hematopoiesis are
frequently seen in the liver and occasionally observed in the
spleen, lymph nodes or thymus Yoder et al (2002)

Different
neonatal developmental stages

Pediatric hematologic values change
markedly in the first weeks and months of life. As a result, many
variables influence the interpretation of what might be
considered normal values at the time of birth. It is important to
provide age appropriate pediatric hematologic values that span
from neonatal life through adolescence. The pediatric population
can be divided into three different developmental
groups;

• 1. The neonatal period, which
  represents the first four weeks of life.

• 2. Infancy, which incorporates the
  first year of life.

• 3. Childhood, which spans form age
  1 to puberty (8 to 12 years).

The RBC count increases during the first 24
hours of life, remains at this plateau for about 2 weeks and then
slowly declines. This elevation may be explained by the partial
in utero anoxia that becomes more progressive as the fetus grows.
Anoxia, the trigger for increased secretion of erythropoietin,
stimulates erythropoiesis Zaizov & Matoth (1976). At birth,
the physiologic environment changes and the fetus makes the
transition from its placenta- dependent oxygenation to the
increased tissue oxygenation of the lungs. After this brisk
elevation, there is a continuous decline in the number of RBCs.
The mechanism may be a decrease in the secretion of
erythropoietin Pahal et al (2000). Studies show erythropoietin
levels before birth equal to or greater than adult levels with
gradual drops to near zero a few weeks after birth Christensen et
al (2000). This corresponds with the physiologic anemia seen at 5
to 8 weeks of life. The span of erythrocytes in full term infants
is shorter than that of adult erythrocytes; the life span of RBCs
in premature infants is considerably shorter. The more immature
the infant is, the greater the degree of reduction.

Erythrocyte
morphology at birth

Segal & Palis (2006) reported that
early normoblasts are megaloblastic, hypochromic and irregulary
shaped. During hepatic hematopoiesis, normoblasts are smaller
than the megaloblasts of the yolk sac but are still macrocytic.
Erythrocyte morphology remains macrocytic from the first 11 weeks
of gestation until day five of post natal life, Soldin et al
(2005).The macrocytic RBC morphology gradually changes to the
characteristic normocytic normochromic morphology. Orthochromic
normoblasts frequently are observed in the full term infant on
the first day of life but disappear within post natal days three
to five. Nucleated RBC may persist longer than a week in immature
infants. The presence of nucleated RBCs for more than five days
suggests hemolysis, hypoxic stress or acute infections Luchtman-
Jones et al (2006).

Reticulocytes

An apparent reticulocytosis exists during
gestation decreasing from 90% reticulocytes at 12 weeks
gestation. Reticulocytosis persists for about 3 days after birth
then declines abruptly to 0.8% on postnatal days 4 to 7. At 2
months, the number of reticulocytes increases slightly followed
by a slight decline from 3 months to 2 years, when adult levels
are attained Thomas et al (1983).

Anemia of the
neonates

The hemoglobin(Hb) concentration of term
infants decreases during the first 5 to 8 weeks of life a
condition called physiologic anemia of infancy. Infants born
prematurely also experience a decrease in Hb concentration which
is termed physiologic anemia of prematurity Cavaliere T A (2004).
Additionally, the fetal RBC has a shorter life span than normal
erythrocytes. Studies conducted with chromium labeled newborn
RBCs, corrected for the elution rate of chromium from newborn
cells estimated a survival time of 60 to 80 days Segal &
Palis(2006). This physiologic anemia is not known to be
associated with any abnormalities in the infant. The reasons for
the shortened life span are unclear. Along with Hb, there is a
reduction in the number of RBCs, a decrease in the reticulocytes
percentages and undetectable levels of erythropoietin. When the
lungs replace the placenta as the source of oxygen, the increased
oxygen saturation of the blood may generate a negative feed back
response, slowing erythropoietin production Geaghan S M (1999)
and erythropoiesis Halvorsen & Finne(1968).

White blood cell
and Platelet values of the newborn

Fluctuations in the number of WBCs are
common at all ages but are greatest in infants. Leukocytosis is
typically at birth for full term and preterm infants alike at the
first 12 hours of life Dallman P R (1977). There is an excess of
polymorphonuclear Neutrophils, bands and occasional
metamyelocytes with no evidence of disease. During the subsequent
days the leukocyte count continue to decrease, the trend
continues until fourth year. Neutrophilic leukocytes of Term and
preterm infants show a greater absolute neutrophil count than of
older children, who normally maintain higher
lymphocytes.

The platelet count usually ranges from 100
to 400 X 109/L for full term and preterm infants respectively.
Low normal platelet counts have been associated with birth
trauma. Platelets of newborn show great variation in size and
shape. Adult reference ranges are achieved by 6 months of age.
Thrombocytopenia in premature infants should be considered
abnormal not physiologic Christensen R D (2000).

INTRODUCTION TO
THE ELDERLY HEMATOPOIESIS

The life expectancy and quality of life of
the elderly have improved dramatically in recent years. Global
aging is occurring at a record breaking rate. Although age 65 is
considered the mean geriatric age, this number is constantly
rising with 122 as the upper limit. The World Health Organization
reports that by 2050, one fifth of the global population will be
adults 65 years and older (Federal interagency form on aging
related statistics-2006).

The elderly can be roughly divided into
three age categories according to Zauber & Zauber
(1987);

• 1. The young- old age 65 to
  74

• 2. The old- old age 74 to
  84

• 3. The very old age 85 and
  older.

The care of the elderly has become a
growing trend as the life expectancy of the population continues
to increase. Disease and disabilities are not a function of age,
although age may be a risk factor for many diseases. With the
increase in the aging population, the incidence of age related
health conditions also is likely to increase.

Geriatric medicine is a rapidly growing
branch of medicine. Inappropriate reference values may lead to
unnecessary testing and investigations or more importantly, they
may fail to detect a critical underlying disease. A growing
concern about the interpretation of hematologic data in context
with age is due partly to the tremendous heterogeneity of the
aging process and partly to the difficulty in separating the
effects of age per se from the effects of occult diseases that
accompany aging Chatta & Dale (1996).

Aging process and
Hematopoiesis

The aging process is associated with the
functional decline of several organ systems, such as
cardiovascular, renal, musculo-skeletal, pulmonary and bone
marrow reserve. Certain cells lose their ability to divide
(example nervous tissue, and muscles) whereas bone marrow and the
gastrointestinal mucosa, remain mitotic. Marrow cellularity
begins at 80% to 100% in infancy and decreases to about 50% after
30 years, followed by a decline to 30% after age 65 years
Lansdorp P M (1997).

Assessment of
Hematologic parameters in healthy elderly
adults

Erythrocytes

Anemia is frequently found in the elderly.
Males characteristically have higher Hb levels than females,
owing to the stimulating effects of androgens on erythropoiesis,
however the difference narrows with decreasing androgen levels in
elderly males Allan & Alexander (1965).

Leukocytes

In the healthy elderly with no underlying
pathologic condition, there are no statistically significant
differences in the total leukocyte count or WBC differential
between old-old compared with middle- aged adults Salive et al
(1992).

Lymphocytes

Immune senescence, age –related
defects in lymphopoiesis, affects humoral and cellular immunity.
The thymus disappears by early middle age and adults depend on T
lymphocyte response in the secondary tissue Globerson A (1995).
The number of naïve T cells decreases in the elderly,
increasing the dependency on memory T cells. T cells of the
elderly have impaired responsiveness to mitogens and antigens as
a result of a decreased expression of co-stimulator CD28. B
lymphocyte function depends on T cell interaction. When T cell
inadequacies occur, there may be a decreased ability to generate
an antibody response Song et al (1993).

Platelets

The platelet count is not significantly
changed with age. There have been reports of increased levels of
ß- Thromboglobulin and platelet factor 4 in the a granules
and decreased platelet membrane protein kinase C activity
Grubeck-Lobenstein B (1997).

Anemia and the elderly

The World Health Organization defines
anemia as hemoglobin less than 13 g/dl in males and less than
12g/dl in females. Based on this definition, the prevalence of
anemia in males older than 85 years is approximately 44% Smith D
(2002). It is unclear however, if the low Hb levels observed in
the elderly are due to disease or normal changes related to
aging. Most elderly persons maintain a normal blood count and
elderly individuals with low Hb levels have an underlying health
problem. The variables contributing to anemia are a decrease in
bone marrow function, a decline in physical activity,
cardiovascular disease and chronic inflammatory disorders. Iron
deficiency anemia and anemia of chronic inflammation are the most
common causes of anemia in the elderly.

To lesser degree, the elderly are prone to
anemias such as sideroblastic, aplastic, hemolytic, myelophthisic
or anemia due to protein calorie malnutrition. Hypoproliferation
or decreased production of RBCs is a common form of anemia in the
elderly. Initially, this form of anemia was called unexplained
anemia, senile anemia and anemia of senescence. Hypoproliferative
anemia often occurs secondary to iron deficiency, vitamin B12 or
folate deficiency, renal failure, hypothyroidism, chronic
inflammation or endocrine disease Howe R B (1983). Often the
etiology of anemia in the elderly cannot be
determined.

Hematologic neoplasia in older
individuals

Although hematologic malignancies may occur
at any age, certain disorders are common in those older than 50
years.

Myelodysplastic
syndrome

Myelodysplastic syndromes a heterogenous
group characterized by a defect in the hematopoietic stem cell
that may affect multiple cell lineages are diagnosed more
frequently in the elderly and in some patients myelodysplastic
syndrome terminates in acute leukemia.

Myeloproliferative
disorders

Myeloproliferative disorders are monoclonal
proliferations of hemapoietic stem cells with overaccumulation of
RBCs, WBCs or platelets in various combinations. The average age
of patients with polycythemia vera is 60 years. The incidence of
chronic myelogenous leukemia increases after age 50. Chronic
idiopathic myelofibrosis occurs in age between 50 to 70
years.

Chronic Lymphocytic Leukemia
(CLL)

CLL is the most common cause of
lymphocytosis in the elderly and constitute 30% of all leukemias
seen in western countries. The onset is usually asymptomatic at a
median age of 60 to 65 years and it occurs twice as often in
males as compared with females Rozman & Montserrat
(1995).

Multiple Myeloma

Multiple myeloma is a plasma cell cancer
characterized by monoclonal gammopathy and multifocal destructive
bone lesions throughout the skeleton. The neoplastic plasma cells
secret complete or incomplete immunoglobulins. The age of peak
incidence for multiple myeloma is 67 years, with 80% of cases
occurring after 60 (American cancer society 2006). It occurs at
an equal frequency in males and female.

Conclusion: The hematological changes are
obvious in both the neonates and the elderly persons and at such,
different hematological variables must be implemented in various
developing stages of the neonates as well as the different
classes of aged elderly individuals. Also among the elderly,
certain hematological disorders are more dorminant and clinicians
should be attentive to this.

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Autor:

Peter Ubah Okeke

2011