approach to anemiia edited.pptx

BDU CMHS Department of Pediatrics and child health
1
Seminar On Approach to Anemia
Moderator : Dr. Yalemwork A.( MD,pediatrician)
Presenter :Dr Tiguaded k.(PCHR1)
2/9/2023 Dr.Tiguaded kindie

OUT LINES
Objectives
Definition
Epidemiology
Classification
Clinical Evaluation
Investigations
Principles of treatment
Common Childhood Anemias
References
2/9/2023 Dr.Tiguaded kindie 2

objectives
At the end of this seminar :
we should define Anemia ,classify and know how to approach a child
with Anemia.
 we should know the commonest causes of Anemia in childhood.

Definition
• Anemia is defined as: a reduction of the hemoglobin concentration or
RBC volume below the range of values occurring in healthy persons.
• In practice anemia most commonly is defined by reductions in one or
both of the following:
HCT: hematocrit is the fractional volume of a whole blood sample
occupied by RBCs, expressed as a percentage.
HGB: this is a measure of the concentration of RBC pigment in whole
blood expressed as gram/dl.

Definition
 WHO’s hemoglobin thresholds to define anemia;
 children 6months to< 5years:11g/dl
 children 5years to <12 years:11.5g/dl
 children 12 years to <15 years:12g/dl
 non pregnant women :12g/dl
 pregnant women :11g/dl
 men>=15 years :13g/dl

Epidemiology
• Anemia is a significant global problem affecting children and pregnant
women.
• In 2019 G.C,global anemia prevalence was 39.8% in children aged 6-
59 months, equivalent to 269 million children with anemia.
• The prevalence of Anemia in children under five was highest in the
Africa region 60.2%.
• Since 2000,the global prevalence of anemia in under 5 has slowly
decreased over the years from 48% to 39.8%.

Anemia is a significant global health problem affecting children
and reproductive-age women

Cont. …
In EDHS 2016,56% of children6-59 month suffered from some
degree of anemia.
• Mild anemia….25%
• Moderate anemia….28%
• Severe anemia….3%
The prevalence of anemia decrease with age from high of 77% among
children age 6-11 month to 40% among children age 48-59 month.
The lowest prevalence of anemia is among children living in Amhara
region(41%) and highest in children living with Somali region(83%).

Classification of anemia
• It can be classified based on etiology or morphology.
• Morphologic classification
-Normocytic
-Microcytic
-Macrocytic
• Etiologic classification
-Increased RBC destruction
-decreased RBC production
-Blood loss

Clinical evaluation
• The evaluation of a child with anemia begins with a thorough history.
Age,Sex,Race and Ethnicity
 symptom characteristics including
 onset and severity
 symptom of hemolysis
 bleeding symptoms
Past medical history
History anemia
Underlying medical condition

Age Causes of anemia
0-3months Blood loss
 Immune hemolytic disease
 Congenital infection
 Twin-twin transfusion and
 Congenital hemolytic anemia (eg, hereditary spherocytosis,
G6PD deficiency)
3-6months hemoglobinopathy.
Toddlers, children, and
adolescents
acquired causes of anemia are more likely, particularly iron
deficiency anemia
11

Cont.…
Drug and Toxin exposure
Family history
Dietary history
Developmental history
Developmental delay can be associated with iron deficiency, vitamin
B12 deficiency, and Fanconi anemia.

Contd…..
Physiologic adjustments to anemia include ;
 Increased cardiac output,
 A shunting of blood flow towards vital organs and tissues.
 The concentration of 2,3-DPG increases within the RBCs------ “shift
to the right” of the oxygen dissociation curve reduces the affinity of
hemoglobin for oxygen and results in more complete transfer of
oxygen to the tissues.
 Higher levels of erythropoietin (EPO)

14
 The resultant “shift to
the right” of the oxygen
dissociation curve
reduces the affinity of
hemoglobin for oxygen
and results in more
complete transfer of
oxygen to the tissues.

Physical examination
• The physical examination also may provide important clues to the
cause of anemia.
• Particular focus should be directed to examination of the skin, eyes,
mouth, faces, chest, hands, and abdomen .
• Pallor is assessed by examining sites where capillary beds are visible(
conjunctiva, palm, and nail beds).

Cont.…
• However, the sensitivity of clinical assessment of pallor in these
locations in detecting severe anemia (HGB <7 g/dL) is only
approximately 50 to 60%.
• Patients with hemolytic processes resulting in anemia may present
with signs of scleral icterus, and hepatosplenomegaly resulting from
increased RBC destruction.

Investigation
 Laboratory Studies
 Initial laboratory testing should include haemoglobin, hematocrit,
and RBC indices
 white blood cell (WBC) count and differential, platelet count,
reticulocyte count, and
 examination of the peripheral blood smear.
The need for additional laboratory studies is dictated by the history,
physical exam, and results of this initial testing.

Contd…
• Hgb and HCT: Normal ranges for HGB and hematocrit vary
substantially with age, so it is important to use age- and sex- adjusted
norms.
• Falsely elevated results may be obtained when HGB and HCT values
are measured using capillary samples (eg, finger or heel "sticks).
• Spurious results may also occur with automated counters in the
presence of lipemia, hemolysis, leukocytosis of >50 x 109/L, or high
immunoglobulin levels .

RBC indices
• Mean corpuscular volume :is measured directly by automated blood
cell counters and represents the mean value in femtoliters of the
volume of individual RBCs in the blood sample.
• Normal values for MCV vary based upon age i.e infants have
increased MCV compared with older children.
• MCV is the most useful RBC parameter when evaluating a patient
with anemia and is used to classify the anemia:
Normocytic
Macrocytic and
 Microcytic.

Contd…
• Red cell distribution width −is a quantitative measure of the
variability of RBC sizes in the sample (anisocytosis).
• Normal values vary little with age and are generally between 12 and
14 percent.

Cont …
• Mean corpuscular hemoglobin concentration:is a calculated index
(MCHC = HGB/HCT), yielding a value of grams of HGB per 100 mL
of RBC.
• MCHC values vary depending upon the age and sex of the child.
• MCHC also increases with decreasing gestational age.
• MCHC measurements may vary slightly based upon the technology
used and should be interpreted using the normal range for the specific
laboratory.

Cont ….
Anemia can also be classified on the basis of MCHC:
Hypochromic anemia is defined as anemia with low MCHC ≤32 g/dL.
Normochromic anemia is defined as anemia with MCHC values in the
normal range 33 to 34 g/dL.
Hyperchromic anemia is defined as anemia with high MCHC ≥35
g/dL.

Cont…
• WBC and platelet count — The other cell lines may provide clues to
the underlying cause of anemia.
• Thrombocytosis : is a common finding in iron deficiency.
• Blood smear :. Even if the patient's RBC indices are normal, review
of the blood smear may reveal abnormal cells that can help identify the
cause of anemia.

Cont….
• The following features should be noted:
RBC size
Central pallor
Fragmented cells
Sickle cells
Elliptocytes
Pencil poikilocytes

Cont ….
Basophilic stippling
The presence of numerous nucleated RBCs indicates rapid bone
marrow turnover and is seen with hemolytic processes.
Target cells, as seen in the various hemoglobinopathies, including
thalassemia, as well as in liver disease, and post-splenectomy.

Cont. ….
• The appearance of the patient's leukocytes should also be noted:
Increases in circulating neutrophils suggests the possibility of
infectious conditions.
Hyper segmented neutrophils suggest vitamin B12 or folate
deficiency.
The presence of early white blood cell forms blasts along with anemia
should raise the suspicion of leukemia or lymphoma.

Cont …
• Reticulocyte count :Reticulocytes are the youngest red cells in the
circulation, and are identified by the presence of residual RNA.
• The reticulocyte is reported as a percentage of the RBC population.
• Absolute reticulocyte count = percent reticulocytes x red blood cell
count/L
• reticulocyte percentage of total RBCs during most of childhood is
approximately 1%, with an absolute reticulocyte count of 25,000-
75,000/mm3 x red blood cell count/L.

Cont ….
• In the presence of anemia, EPO production and the absolute
number of reticulocytes should rise .
• Low or normal numbers of reticulocytes
generally represent an inadequate response to anemia.
• Increased numbers of reticulocytes represent a normal bone marrow
response to ongoing RBC destruction , sequestration, or loss.

General principles of management
Supportive
Supplemental oxygen
Fluid administration-hypovolemic patients
• Blood transfusion

CHILDREN AND ADOLESCENTS
1. Maintain stable status with acute loss of >25% of circulating blood
volume.
2. Maintain hemoglobin >7.0 g/dL in the perioperative period.
3. Maintain hemoglobin >12.0 g/dL with severe cardiopulmonary
disease.
4. Maintain hemoglobin >12.0 g/dL during extracorporeal membrane
oxygenation.
5. Maintain hemoglobin >7.0 g/dL and symptomatic chronic anemia.
6. Maintain hemoglobin >7.0 g/dL and marrow failure.

INFANTS ≤4 Month old
1. Maintain hemoglobin >12.0 g/dL and severe pulmonary disease.
2. Maintain hemoglobin >12.0 g/dL during extracorporeal membrane
oxygenation.
3. Maintain hemoglobin >10.0 g/dL and moderate pulmonary disease.
4. Maintain hemoglobin >12.0 g/dL and severe cardiac disease.
5. Maintain hemoglobin >10.0 g/dL preoperatively and during major
surgery.
6. Maintain hemoglobin >7.0 g/dL postoperatively.
7. Maintain hemoglobin >7.0 g/dL and symptomatic anemia.

Iron-Deficiency Anemia
• Iron deficiency is the most widespread and common nutritional
disorder in the world.
• It is estimated that 30–50% of the global population has iron-
deficiency anemia .
• In USA, 8–14% of children ages 12-36 month are iron deficient ,and
30% of this group progresses to iron-deficiency anemia .
• A full-term newborn infant contains about 0.5 g of iron,
compared to 5 g of iron in adults.

Contd …
• iron deficiency anemia in children can be defined as:
1) For children 6 months to <5 years:
Ferritin <12 micrograms/L and
Hemoglobin <11 g/dL .
2) For children 5 to <12 years:
Ferritin <15 micrograms/L and
Hemoglobin <11.5 g/dL

Pathophysiology

Contd …
About 75% is bound in the heme proiteins
The remainder is bound in the storage protiens –ferritin and
hemosiderin
Small portion<3%is bound in the critical enzymes-catalase
and cytochrome
In healthy adults <5% iron comes from dietary sources
The remainder is from senescent RBCs
In infants and children about 30% iron needs should come
from diet due to rapid growth and increased muscle mass that
occurs in this age range.

Contd …
Peak prevalence occurs during late infancy and early childhood when the
following may occur:
Rapid growth with exhaustion of gestational iron.
 Low levels of dietary iron.
 Blood loss due to internal or external bleeding.
 Complicating effect of cow’s milk-induced exudative enteropathy due
to whole cow’s milk ingestion.
A second peak is seen during adolescence due to rapid growth and suboptimal
iron intake.
This is amplified in females due to menstrual blood loss.

Cont …
 A dietary intake of 8-10 mg of iron daily is necessary to maintain
iron levels
Absorbed in the proximal duodenum with the assistance of gastric
acid
Usually occurs at 9-24 months of age

Etiologies
 Deficient intake
 Inadequate absorption
 Increased demand
 Blood loss
 Impaired absorption
 Inadequate presentation to erythroid precursors

Clinical manifestation
 Most children with iron-deficiency anemia are asymptomatic and are
identified by routine laboratory screening at 9-12 mo of age
 Pallor is the most recognized clinical sign of iron-deficiency anemia but is
not usually visible until the hemoglobin falls to 7-8 g/dL. noted as pallor of
the palms, palmar creases, nail beds, or conjunctivae(capillary dense areas)
 Older individuals may report cold intolerance, fatigue, exercise-induced
dyspnea, or decreased mental acuity.

Cont..
 When the hemoglobin level falls to <5 g/dL, irritability, anorexia, and
lethargy develop, and systolic flow murmurs are often heard.
 If the hemoglobin continues to fall,tachycardia and high output
cardiac failure can occur.

Cont…
 Nonhematologic systemic effects
 Both iron deficiency and iron-deficiency anemia are associated with
impaired neurocognitive function in infancy.
 Increased risk of seizures, strokes, breath-holding spells in children and
exacerbations of restless legs syndrome in adults
 Pica
 Pagophagia

Laboratory
 Sequence of biochemical and hematologic events occurs
First, tissue iron stores are depleted - reduced serum ferritin
RDW(>14.5%) is earliest detectable laboratory change
Next, serum iron levels decrease---serum transferrin increases and
the transferrin saturation falls below normal.
 As iron stores decrease---hemoglobin synthesis is impaired.---IDA

Cont…
 White blood cell count is normal,
 Thrombocytosis is often present.
 Thrombocytopenia is occasionally seen
 microcytic anemia with a high RDW and reduced RBC count
 Stool for occult blood
 Bone marrow iron staining (Prussian Blue Stain
of Bone Marrow)…gold stanadard

Stages of iron depletion
Iron depletion: This occurs when tissue stores are decreased without a
change HCT or serum iron.
Iron deficient erythropoiesis: This occurs when reticuloendothelial
macrophage iron stores are completely depleted.
• The serum iron level drops and the total iron-binding capacity
increases without a change in the hematocrit.
Iron deficiency anemia :This is associated with erythrocyte
microcytosis, hypochromia, increased RDW, and increased FEP.

Treatment
 Ferrous salts (Sulfate, gluconate , fumarate - -most often ferrous sulfate)
provides inexpensive and effective therapy.
 A daily total dose of 3-6 mg/kg of elemental iron in 1 or 2 doses is
adequate ,with the higher dose used in more severe cases.
 The maximum dose is 150-200 mg of elemental iron daily.

Cont …
 Because a rapid hematologic response can be confidently predicted in
typical iron deficiency, blood transfusion is rarely necessary.
 It should only be used when
heart failure is imminent, or
if the anemia is severe with evidence of substantial ongoing blood loss.

Therapeutic response

DDX of microcytic anemia that fails to
respond to iron

Megaloblastic anemia
 Megaloblastic anemia describes a group of disorders that are caused by
 impaired DNA synthesis .
 Red blood cells (RBCs) are larger than normal at every developmental stage, and there
is maturational asynchrony between the nucleus and cytoplasm of erythrocyte.
 All are characterized by;
 Ineffective erythropoesis
 Macrocytes
 Presence of hyper-segemented neutrophils

Folic acid deficiency
• Biologically active folates are derived from folic acid and serve as1-
carbon donors and acceptors in many biosynthetic pathways.
• To form functional compounds, folates must be reduced to
tetrahydrofolates in a process catalyzed by the enzyme dihydrofolate
reductase.

Cont…
• Humans depend on dietary sources.
• Folate is available in green vegetables and animal organs.
• Although rare, megaloblastic anemia as a consequence of folate
deficiency has its peak incidence at 4-7 mo of age, somewhat earlier
than iron-deficiency anemia.

Cont….
Heat labile and water soluble
Absorption is throughout small intestine
Body stores are limited, megaloblastic anemia occur 2-3 months
after folate free diet
Goat milk is deficient

Etiology
• Inadequate Nutrition
• Defects in Absorption
• Increased Requirements or Losses
• Disorders of Cellular Metabolism

Clinical manifestation
Irritability
Failure to gain weight
Chronic diarrhea
Hemorrhage in advanced cases
Hypo-gammaglobulinemia, severe infections,
Failure to thrive,
seizures, developmental delay, and intellectual disability

laboratory
Macrocytic anemia
Low serum folate or serum RBC folate level
Levels of RBC folate are a better indicator of chronic deficiency
Reticulocyte count is low,
Nucleated RBCs with megaloblastic morphology (Hypersegmented
&large neutrophils)

Cont…
• Normal serum folic acid levels are 5-20 ng/mL
• In folate deficiency ,levels are <3ng/mL
• The normal RBC folate level is 150-600 ng/mL of packed cells.
• Serum activity of lactate dehydrogenase, a marker of ineffective erythropoiesis, is
markedly elevated.

Treatment
Folic acid 0.5 mg-1 mg/day for 3-4 weeks
Smaller doses of folate (0.1 mg/day) may be used for 1 wk as a diagnostic
test because a hematologic response can be expected within 72 hr.
Maintenance therapy with a multivitamin (containing 0.2 mg of folate) is
adequate.
Transfusions are indicated only when the anemia is severe or the child is
very ill.

Response to Folic Acid Treatment
 Within 1-2 days, the appetite improves
 a rise in reticulocytes in 24 days, reaching a peak at 4-7 days
 a return of hemoglobin levels to normal in 2-6 week
Leukocytes and platelets increase and megaloblastic changes in the marrow
diminish within 24-48 h

Vitamin B12 deficiency
 Cobalamin is synthesized exclusively by microorganisms
 Humans must rely on dietary sources (animal products)
 The cobalamins are released by the acidity of the stomach
 Combine there with intrinsic factor (IF).
 IF – B12 Complex binds to receptor in terminal ileum for absorption.
 Older children and adults have sufficient vitamin B12 stores to last 3–5 yrs

Etiology
• Inadequate dietary intake of Cbl
• Lack of IF
• impaired intestinal absorption of IF-Cbl
• Absence of transport protein
• surgery

Clinical features
 Common findings include pallor, glossitis, vomiting, diarrhea, and icterus
 Neurologic symptoms
 paresthesia, sensory deficits, hypotonia, seizures,
 developmental delay/regression, and neuropsychiatric changes.
 Neurologic problems from vitamin B12 deficiency may occur in the absence
of any hematologic abnormalities.

Investigation
Low serum vitamin B12 level
Serum concentrations of
Methylmalonic acid and
Homocysteine are usually elevated.
Excessive excretion of methylmalonic acid in the urine
Serum iron and folic acid are normal or elevated.
Serum LDH activity is markedly increased

Treatment
The cause of vitamin B12 deficiency should ultimately dictate treatment dosage as
well as the duration of therapy
The typical dose for children is 50 to 100 mcg parenterally once per week until the
deficiency is corrected and then
once per month (cyanocobalamin) or
once every other month (hydroxocobalamin)

Response to Vitamin B12 Treatment
• Beginning bone marrow reversal from megaloblastic to normoblastic
cells occurs within 6 h and is complete in 72 h.
• The level of alertness and responsiveness improves within 48 h and
developmental delays may catch up in several months in young
infants.

Cont …
• The reticulocytes begin to increase on the third or fourth days,
rise to a maximum on the sixth to eighth days, and fall gradually to
normal about the twentieth day.

Reference
• Nelson text book of pediatrics 21st edition
• Lanzkowsky’s Manual Of Pediatric Hematology And Oncology, Sixth
E
• Uptodate 2018.
• EDHS 2016

THANK YOU

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