2. Outline
DeFinitiOn OF AneMiA
OVeRVieW OF eRYtHROPOieSiS
ClASSiFiCAtiOnS OF AneMiA
HiStORY AnD PHYSiCAl eXAMinAtiOn
lABORAtORY eXAMinAtiOn
iROn-DeFiCienCY AneMiA
HeMOlYtiC AneMiA
PHYSiOlOgiC AneMiA OF inFAnCY
2
3. DEFINITION OF ANEMIA
Anemia may be defined as a reduction in red blood
cell mass or blood hemoglobin concentration.
In practice, anemia most commonly is defined by
reductions in one or both of the following:
1. Hematocrit (HCT) — The hematocrit is the
fractional volume of a whole blood sample
occupied by red blood cells (RBCs); it is expressed
as a percentage.
3
4. DEFINITION OF ANEMIA cont…
2. Hemoglobin (HGB) — This is a measure of the
concentration of the RBC pigment hemoglobin in
whole blood, expressed as grams per 100 mL (dL)
of whole blood.
The age variation for HGB and HCT is pronounced
in the pediatric population; thus, it is particularly
important to use age and sex adjusted norms when
evaluating a pediatric patient for anemia
4
5. OVERVIEW OF ERYTHROPOIESIS
• Developmental hematopoiesis occurs in three
anatomic stages: mesoblastic, hepatic, and myeloid.
• Fetal erythropoiesis begins with primitive
megaloblastic erythropoiesis; these cells can be
identified at approximately four to five weeks
gestation .
• A transition is made to normoblastic erythropoiesis at
approximately six weeks gestation.
• At this time, blood formation begins in the liver,
which is the primary organ of hematopoiesis from the
third to sixth month of gestation .
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6. OVERVIEW OF ERYTHROPOIESIS cont..
At approximately the third month of gestation,
hematopoiesis begins in the spleen, thymus, and lymph
nodes.
The liver and spleen continue to produce blood cells
into the first week of postnatal life.
Bone marrow hematopoiesis begins around the fourth
month of gestation and increases throughout
intrauterine development.
6
7. OVERVIEW OF ERYTHROPOIESIS cont..
Erythropoiesis decreases dramatically after birth.
Red cell production decreases by a factor of 2 to 3
in the first few days of life and by a factor of 10 in
the week following birth.
This decrease is initiated by the increase in tissue
oxygen level that occurs at birth and is
accompanied by a decrease in erythropoietin
production resulting in the "physiologic anemia of
infancy"
7
8. OVERVIEW OF ERYTHROPOIESIS cont..
Red cell production is at a minimum during the
second week after birth and subsequently rises to
maximum values at approximately three months.
The net result of these changes is an anemia that
typically nadirs at 6 to 9 weeks of age.
Anemia in preterm infants may be more
pronounced because of the shorter life span of
preterm red cells.
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9. CLASSIFICATIONS OF ANEMIA
Anemias may be classified on either
-pathophysiologic mechanisms or
-a morphologic basis.
Physiologic etiologies for anemia may be classified:
Disorders resulting in an inability to adequately produce red
blood cells (i.e. bone marrow depression).
Disorders resulting in rapid RBC destruction (hemolysis)
RBC losses from the body (bleeding)
These categories are not mutually exclusive
9
10. CLASSIFICATIONS OF ANEMIA cont…
Morphologic classification -Anemias may be
classified also according to RBC size (mean
corpuscular volume, MCV), hemoglobin content
(mean corpuscular hemoglobin, MCH), or
hemoglobin concentration (mean corpuscular
hemoglobin concentration, MCHC).
10
11. Approach to the patient
HISTORY AND PHYSICAL EXAMINATION
HISTORY:
When evaluating an anemic child in addition to the age and sex
of the child, Severity and initiation of symptoms
Acute anemia
Chronic anemia
Prior episodes of anemia may indicate inherited forms, whereas
anemia in a patient with previously documented normal blood
counts suggests an acquired etiology.
11
12. HISTORY AND PHYSICAL EXAMINATION cont..
Questions relating to hemolytic episodes:
changes in urine color, jaundice associated with the symptoms
of anemia should be asked.
Any family history of anemia.
symptoms consistent with pica.
Birth history — A birth and neonatal history including
infant and mother's blood type, any history of exchange ,
and a history of anemia in the early neonatal period
should be obtained.
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13. HISTORY AND PHYSICAL EXAMINATION cont..
Physical examination :
Areas of particular importance on the physical examination
include: the skin, eyes, mouth, facies, chest, hands, and
abdomen.
Pallor should be assessed by examining sites where capillary
beds are visible through the mucosa (e.g. conjunctiva,
palm, and nail beds).
Jaundice and hepatosplenomegaly resulting from increased
red cell destruction Patients with hemolytic anemia.
13
14. LABORATORY EXAMINATION
a complete blood count including red blood cell indices,
a reticulocyte count, and a review of the peripheral
blood smear.
Blood smear- a review of the peripheral smear is an
essential part of any anemia evaluation.
– The diameter of a normal RBC should be the same as the
diameter of the nucleus of a small lymphocyte
The mean corpuscular volume (MCV) is perhaps the most
useful RBC parameter used in the workup of anemia
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15. LABORATORY EXAMINATION
Mean corpuscular hemoglobin concentration — The
MCHC is a calculated index (MCHC= HGB/HCT),
yielding a value of grams of HGB per 100 mL of RBC.
Red cell distribution width -the red cell distribution
width (RDW) is a quantitative measure of the variability
of RBC sizes in the sample (anisocytosis).
-values lower than normal indicate the presence of hypochromia.
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18. Approach to Common Causes of Anemia in
Children
Is anemia associated with other hematologic
abnormalities?
If yes, consider
Aplastic anemia
Leukemia
Other bone marrow replacement disorders
Is anemia associated with reticulocytosis?
If yes, usually a consequence of bleeding or
ongoing hemolysis
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19. Approach to Common Causes of Anemia in
Children
Is there associated hyperbilirubinemia or
increased serum lactate dehydrogenase
If yes, usually due to hemolysis
Review of peripheral blood smear
Spherocytes (hereditary spherocytosis, autoimmune
hemolytic anemia, Wilson disease)
Sickle forms (sickle cell disease, sickle-ß-thalassemia)
Target cells (hemoglobin SC disease)
19
20. Approach to Common Causes of Anemia in
Children
Hypochromic RBC, nucleated RBC (homozygous ß-
thalassemia, )
Microangiopathy (hemolytic-uremic syndrome,
thrombotic thrombocytopenia)
Bite cells/blister cells (G6PD deficiency)
20
21. Approach to Common Causes of Anemia in
Children
Is anemia associated with a lower than
appropriate reticulocyte response?
If yes, assess red blood cell size
o Are red blood cells microcytic?
If yes, usually due to defect in hemoglobin
synthesis
Iron deficiency
Hemoglobin E disorders
Lead poisons
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22. Approach to Common Causes of Anemia in
Children
Are red blood cells macrocytic?
If yes, is there neutrophil hypersegmentation
(megaloblastic changes)?
If yes, consider
– Folate deficiency, vitamin B12 deficiency, inborn errors of
metabolism
If no, consider
– Diamond-Blackfan anemia
– Congenital dyserythropoietic anemia
– Pearson syndrome
22
23. Approach to Common Causes of Anemia in
Children
Are red blood cells normocytic?
If yes, consider
Anemia of chronic disease usually (associated comorbid
conditions)
Anemia of renal disease (renal failure)
Transient erythroblastopenia of childhood
Anemia associated with hypothyroidism
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24. IRON BALANCE
The major role of iron in mammals is to carry O2 as part of
hemoglobin.
The majority of iron (75 percent) is bound in heme proteins
(hemoglobin and myoglobin).
The remainder is bound in the storage proteins
ferritin and hemosiderin
3 percent of iron is bound in critical enzyme systems, such as
catalase and cytochromes .
In normal subjects, only a small amount of iron enters and leaves
the body on a daily basis.
the body must protect itself from free iron, which is highly toxic
in that it participates in chemical reactions that generate free
radicals such as singlet O2 or OH–.
Most iron is recycled from the breakdown of old red blood cells
by macrophages of the reticuloendothelial system
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25. Iron-Deficiency Anemia
Lack of sufficient iron for synthesis of hemoglobin is the
most common hematologic disease of infancy and
childhood.
Iron store in the new born is 0.5gm & that of adult is
5gm. For this discrepancy, an average of 0.8mg of iron
must be absorbed each day during the first 15 yr of life.
Normal losses of iron by shedding of cells. So, to
maintain positive iron balance in childhood, about 1mg
of iron must be absorbed each day.
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26. Iron-Deficiency Anemia cont..
Iron is absorbed in the proximal small intestine,
Absorption of iron is about 10%
Nutrient containing 8-10mg of iron is mandatory.
Iron is absorbed two to three times more efficiently
from human milk than from cow's milk, partly because
of differences in calcium content.
Infants breast-fed exclusively should receive iron
supplementation from 4 mo of age.
Adolescents are also susceptible to iron deficiency
because of high requirements due to the growth spurt,
dietary deficiencies, and menstrual blood loss.26
28. Iron-Deficiency Anemia cont..
Etiology. Low birth weight and unusual perinatal
hemorrhage are associated with decreases in neonatal
hemoglobin mass and stores of iron.
Hook worm infestation, peptic ulcer, Meckel
diverticulum, polyp, or hemangioma, or by
inflammatory bowel disease.
In term infants it is unusual before 6 mo and usually
occurs at 9–24 mo of age.
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29. Cont…
Low birth weight
Premature birth
Perinatal blood loss
Poor supplementation
Intestinal malabsorption
Occult blood loss
milk protein–induced inflammatory colitis, peptic ulcer,
Meckel diverticulum, polyp, or hemangioma, or
inflammatory bowel disease
Hook worm infestations & H.pylori
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30. Clinical Manifestations
Pallor is the most important sign of iron deficiency.
In mild to moderate(Hgb levels of 6–10g/dL),
compensatory mechanisms, increased levels of 2,3-
DPG.
Irritability, Pagophagia, When the hemoglobin level falls
below 5g/dL, irritability and anorexia are prominent.
Tachycardia and cardiac dilation occur, and systolic
murmurs are often present
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31. Cont…
Impaired psychomotor and/or mental development
Cognitive impairment in adolescents
Palmar, nailbed, and conjunctival pallor
Pagophagia, the desire to ingest unusual substances such as
ice or dirt
Irritability and anorexia characteristic of advanced cases
Attention span, alertness, and learning in both infants and
adolescents is decreased
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32. Cont…
Typical of IDA
KOILONYCHIA( SPOON NAILS)
BLUE SCLERA
PICA & PAGOPHAGIA
PATERSON-KELLY/PLUMMER-VINSON SYNDROME
Dysphagia
Oesophageal web
Atrophic glossitis
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33. Laboratory Findings
In progressive iron deficiency, a sequence of biochemical and
hematologic events occurs.
First, the tissue iron stores represented by bone marrow
hemosiderin disappear.
Next, serum iron level decreases, the iron-binding capacity of
the serum (serum transferrin) increases, and the percent
saturation (transferrin saturation) falls below normal.
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37. Treatment
The regular response of iron-deficiency anemia to
adequate amounts of iron is an important diagnostic and
therapeutic feature.
Oral administration of simple ferrous salts (sulfate,
gluconate, fumarate) provides inexpensive and
satisfactory therapy.
Tolerable in young children unless there is
malabsorption.
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38. Treatment…
General principles of iron treatment
Iron is absorbed in the duodenum & pro.jejunem
Shouldn’t be given with food
Best absorbed in a mildly acidic media
UGI discomfort is directly related to the amount of iron
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39. Treatment…
Oral preparation
Ferrous sulfate 65mg of elemental iron
Ferrous fumarate 106mg of elemental iron
Ferrous gluconate 28-36mg of elemental iron
Ferrous sulfate elixir 44mg/5ml
Side effect
GI upset
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40. Cont…
4–6 mg/kg /day of elemental iron in 3 divided doses.
Blood transfusion: if Hgb is less than 4mg/dl transfuse with
packed or whole blood.
Prevention- iron-fortified formula or cereals during infancy
(started at 4-6 months for term and earlier for preterm )
Duration of treatment
Continue after normalization of HGB to replenish the iron
stores
3-6months after normalization of HGB
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41. Responses to Iron Therapy in Iron-
Deficiency Anemia
Time After Iron
Administration
Response
12–24 hr Replacement of intracellular iron enzymes;
subjective improvement; decreased
irritability; increased Appetite
36–48 hr Initial bone marrow response; erythroid
hyperplasia
48–72 hr Reticulocytosis, peaking at 5–7 days
4–30 days Increase in hemoglobin level
1–3 mo Repletion of stores
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42. Hemolytic anemias
Different ways of classification of causes of HA
Intracorpuscular/ Extracorpuscular
Inherited/ Acquired
Intravascular/ extravascular
Immune-mediated/ non-immune mediated
Immune mediated
Warm/ cold Antibody
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44. Definitions and Classification of
Hemolytic Anemias
Hemolysis is defined as the premature destruction of red blood
cells (RBCs).
Anemia results when the rate of destruction exceeds the capacity
of the marrow to produce RBCs.
Normal RBC survival time is 110–120 days.
0.85% of the most senescent RBCs are removed and replaced
each day.
During hemolysis, RBC survival is shortened, the RBC count falls,
erythropoietin is increased, and the stimulation of marrow activity
results in heightened RBC production.
Elevated reticulocyte count
Hemolysis
acute blood loss
replacement therapy for iron, vitamin B12, or folate deficiency.
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45. DIAGNOSTIC APPROACH
Classic case
New onset of pallor or anemia
Jaundice ( high indirect bilirubin)
Gallstones
Splenomegaly
Presence of circulating spherocytic RC
Increased LDH
Decreased serum haptoglobin
+ Coomb’s test
High retic % or ARC
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48. Physiologic Anemia of Infancy
Normal newborn infants have higher hemoglobin and hematocrit levels
with larger red blood cells (RBCs) than older children and adults.
Within the first week of life, a progressive decline in hemoglobin
level begins and persists for 6–8 wk.
HGB-oxygen saturation increases from 50-95%.
High oxygen affinity fetal HGB replaced by low oxygen affinity
adult HGB.
48
49. Cont…
Factors involved.
With the onset of respiration at birth, considerably more
oxygen is available for binding to hemoglobin, and the
hemoglobin-oxygen saturation increases from 50 to 95% or
more.
developmental switch from fetal to adult hemoglobin
synthesis actively replaces high-oxygen-affinity fetal
hemoglobin with lower-oxygen-affinity adult hemoglobin
the increase in blood oxygen content and tissue oxygen
delivery downregulates EPO production
49
50. Cont…
The hemoglobin concentration continues to decrease until
tissue oxygen needs are greater than oxygen delivery.
Normally, this point is reached between 8–12 wk of age,
when the hemoglobin concentration is 9–11 g/dL.
As hypoxia is detected by renal or hepatic oxygen sensors,
EPO production increases and erythropoiesis resumes.
The iron previously stored in reticuloendothelial tissues can
be used for hemoglobin synthesis
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51. physiologic anemia (Premature
infants )
The decline in hemoglobin level is both more extreme and
more rapid.
The same factors are operative as in term infants, but they
are exaggerated.
Short survival of the RBCs of premature infants
Rapid expansion of the RBC mass that accompanies growth.
Inadequate synthesis of EPO in response to hypoxia.
Blunted EPO response seen in premature infants.
TREATMENT.
Physiologic anemia requires no therapy other than folic acid
and iron.
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