Anemia

Anemia

Most common bleeding disorder in children specially to

those from poor socio economic group.
It is defined as reduction in number and quality of red
blood cells when the hemoglobin content is below the
normal level for particular age group, resulting in
decreased oxygen carrying capacity.
WHO has given the cut-off points of Hb level
for different age groups for diagnosis of
anemia:
 Children 6 months to 6 years – 11 g/dl
 Children 6 to 14 years – 12 g/dl
 Above 14 years – male – 13g/dl and
female – 12 g/dl.
Contd.
At all ages mean corpuscular hemoglobin concentrate
should be 34.
Values below 34 indicate hypochromic RBC, which is
usually found in iron deficiency anemia.
WHO grading of anemia:
 Hb level between 10g/dl and cut off point – mild
anemia
 Hb level between 7g/dl to 10g/dl – moderate anemia
 Hb level below 7 g/dl – severe anemia
Contd.

Clinical grading of anemia:

According to clinical observations, the grading of
anemia is done as:
 Pallor
observed in conjunctiva and mucous
membrane only- mild anemia
 Pallor observed in skin- moderate anemia
 Pallor
observed in palmar crease along with skin and
mucous membrane- severe anemia
Causes of anemia:
1. Impaired RBC production
Due to deficiency of hemopoeitic factors in nutritional
deficiency like iron deficiency anemia , folic acid
deficiency, vitamin B12,B6,C deficiency
2. Increased destruction of RBC ( hemolytic anemia)
I. Hemolysis due to intrinsic factors
 Abnormal hemoglobin synthesis – thalassemia , sickle
cell disease
 Enzymatic defect – glucose 6 phosphate
dehydrogenase deficiency
 Abnormalitiesin RBC membrane or structural defects
of RBC – hereditary spherocytosis
II. Hemolysis due to extrinsic factors
 Infections- malaria , kalazaar
 Antibodyreaction ABO,RH isoimmunization ,
autoimmune hemolytic anemia, lupus
 Drugs such as primiquine , phenytoin
 Poisoning such as lead
 Burns
 Splenomegaly
3. Increased blood loss (hemorrhagic anemia)
 Acute – trauma,epistaxis
 Chronic – hookworms, chronic dysentery,
oesophageal varices.
4. Decreased RBC production (bone marrow
depression)
 Primary –Hypoplasia,aplasia
 Secondary – irradiation, infections, chronic
illness,
 Classification of anemia
According to RBC morphology anemia can be classified as:
 Microcytic hypochromic anemia – it occurs in iron deficiency
anemia and ineffective RBc production
 Normocytic normochromic anemia – it is found in impaired
cell production and hemolysis
 Macrocytic anemia – it develops due to :
 Megaloblastic erythropoiesis –in nutritional deficiency , drug
toxicity and malabsorption
 Nonmegaloblastic erythropoiesis – in chronic hemolytic
anemia,liver disease and hypothyroidism.
Iron-Deficiency Anemia (IDA)

 Most common etiologic factor

 common in infancy because both breast as well as
cow milk do not provide the baby’s needs for iron.
 poor iron stores in premature babies so that, at about
third month (the time for maximal physiologic
reduction of hemoglobin)
 Twins commonly become iron deficient. At times,
only one of them may suffer.
Contd.
 Preschool age and adolescence are particularly more
vulnerable for IDA because of rapid somatic growth.

 In older children, the causes include

• inadequate intake
• Malabsorption
• Infection
• chronic blood loss
Clinical Features

 Progressive pallor
 Anorexia
 Tiredness
 failure to thrive
 atrophy of tongue papillae
 pica
 koilonychia.
 Diarrhea is often present.
 In severe anemia, spleenomegaly, cardiomegaly
 Hemic murmur (soft systolic, having maximal intensity over
the base and changing with position) is common.
 Diagnosis

 microcytic hypochromic anemia along with reduced body/serum

iron.
 Peripheral smear examination shows anisopoikilocytosis (variance
in size and shape of RBC)and polychromasia.(abnormally high
number of immature red blood cells).
 MCV, MCH and MCHC are reduced.
 Contd..
 Red Cell Distribution Width, a measure of variation of
red cell size is increased.
 Mild reticulocytosis, leukocytosis and thrombocytosis.
 Serum iron is reduced (<30 mg/dl is considered
diagnostic), so is serum ferritin(<10 ng/ml).
 Total iron binding capacity (TIBC) over 400 mg/dl
strongly suggests IDA.
Management
iron may be administered orally or parenterally.
A. Oral therapy –
 The dose of elemental iron is 3-6 mg/kg/day in 3 divided
doses.
 Most economic and most easily available one is the simple
ferrous sulfate, containing 20% iron and available as 200 mg
tablets.
 Oral iron,in any form, causes gastric irritation if given in
excess dose.
 The side-effects of oral iron include nausea,vomiting, diarrhea,
constipation, abdominal cramps,staining of teeth and tongue
and discoloration of stools.
 For optimal absorption, iron dose should be
administered in between meals.
 Concurrent administration of vitamin C enhances its
absorption whereas foods rich in phytates (cereals)
and phosphates (milk) reduce it.
 The total duration of treatment varies from 3 to 6
months.
B. Parenteral therapy
 Dose of parenteral iron (intravenous infusion or intramuscular)
is calculated as follows:

 Iron required = 2.5 × body weight (kg) × Hb deficit(Hb deficit

is the difference between measured and desired values of Hb).

 An additional 20-30% of the calculated dose is included to

replenish the stores.
 Blood transfusion should be reserved for life threatening
situations when anemia is very severe and has associated
symptoms warranting a rapid rise in hemoglobin level.
MEGALOBLASTIC ANEMIA

 Megaloblastic changes occur due to deficiency of B12 and

folic acid and in certain inherited disorders involving both
micronutrients.
 Clinical features and usually employed hematological tests do
not distinguish whether folate or B12 deficiency is the cause in
a given case.
Etiology

 Megaloblastic anemia during infancy and early childhood is

more often due to folate deficiency
 That seen among older children results from deficiency of
B12.
 However, recent evidence suggests that even b12 deficiency is
a frequent cause of megaloblastic anemia in infants and young
children. Very often deficiency of both exists.
 Deficiency of B12
In children in developing countries, commonest cause
of B12 deficiency is nutritional.
 Children born to poor /vegetarian mothers who are B12 deficient
have poor stores at birth.
 If these children are exclusively fed on breast milk for unusually
prolonged period, they develop B12 deficiency.
 Among older children, diseases of small intestine resulting in
malaborption (tropical sprue), gastritis, gastrectomy, intrinsic
factor deficiency (pernicious anemia) and fish tape worm
infestation are other causes. Selective B 12 malabsorption is also
described.
 Folate Deficiency
Like B 12 deficiency, most common cause of folate
deficiency is also nutritional.
 Maternal deficiency affecting fetus and infant is a frequent
cause.
 Other causes include goat milk feeding, conditions with
increased requirement (prematurity, chronic
hemolytic anemias), malabsorptive states (tropical
sprue and celiac disease), anticonvulsant therapy and anti-
folate drug therapy.
 Clinical Features

 Other than pallor, children with megaloblastic anemia have

apathy, anorexia, hypotonia and developmental
retardation/regression.
 Hyperpigmentation of knuckles and terminal phalanges is a
common finding described in patients from south-east Asian
region.
 Glossitis with smooth, red, cracked tongue is characteristic.
 megaloblastic anemia is a panmyelopathy (abnormal condition of
all the blood-forming elements of the bone marrow)and hence
fever due to infections
resulting from neutropenia is quite common.
Contd.
 Bleeding manifestations due to thrombocytopenia are
observed in up to 25-30% cases.
 Mild to moderate enlargement of liver and spleen is seen.
 Megaloblastic anemia is frequently seen in cases with
infantile tremor syndromes. Neurological syndrome
associated with B 12 deficiency (subacute combined
degeneration of spinal cord).
 Diagnosis

 Hematological findings include low Hb and macrocytosis,

anisocytosis, poikilocytosis and hyper segmented polymorphs on
peripheral smear examination.
 RBC count is low. MCV is increased. Reticulocyte count is low.
 Pancytopenia has been seen in 40-70% cases of megaloblastic
anemia.
 Bone marrow is hyperplastic with ineffective erythropoiesis and
“megaloblastic changes”
 Serum levels of cobalamin and folate are reduced in respective
deficiency.
 Schilling test is performed to diagnose intrinsic factor deficiency.
 Management
 Administration of folate and B12
 Folic acid in dose as small as 200-500 mcg/day may lead to
adequate response but usually dose of 5 mg orally daily is
administered
 Therapy for 6-8 weeks or longer is usually required.
 B12 deficiency is usually treated with injection of b12 given one or
two times per week.

 Tremors may occur in some patients after administration of such a

large dose. Hence, 250 mg weekly for infants and 500 mg weekly
for older children is a better regimen.
 Concomitant administration of iron and correction of malnutrition
is generally required.
THALASSEMIA(Cooley Anemia, Mediterranean Anemia)

 The word thalassemia is a greek term derived from

thalassa, which means 'the sea' (referring to the mediter­
ranean sea) and emia, which means 'related to blood'.
 Thalas­semias, caused by defects in the globin gene.
 The defects are inherited in an auto­somal recessive
manner.
Pathophysiology
 Normal postnatal Hgb is composed of two α-
and two β-polypeptide chains.
 In β-thalassemia, there is a partial or complete
deficiency in the synthesis of the β-chain of the
Hgb molecule.
 Consequently, there is a compensatory increase
in the synthesis of α-chains, resulting in
defective Hgb formation.
 This unbalanced polypeptide unit is very
unstable; when it disintegrates, it damages
RBCs, causing severe anemia.
 To compensate for the hemolytic process, an
overabundance of erythrocytes is formed
unless the bone marrow is suppressed by
transfusion therapy.
 Excess iron from packed RBC transfusions
and from the rapid destruction of defective
cells is stored in various organs
(hemosiderosis).
 Types
On the basis of severity
1. Thalassemia major:
Severe form also known as cooley anemia/mediterrenian anemia.
Homozygous state of disease means thalassic genes (B chain are inherited from
both parents and production of chain is markedly reduced.
Erythropoeisis becomes ineffective leading to hemolysis and anemia.
This further stimulates erythropoietin resulting more ineffective erythropoiesis.
This results in expansion of medullary cavity of various bones.
Extramedularry hematopoiesis causes enlargement of liver and spleen.
The iron released from breakdown of RBcs and transfused blood cells cannot be
utilized for hemoglobin synthesis which results in hemisderosis.
2. Thalassemia minor
 Mildest form.
 May be heterozygous inheriting only one mutant or beta thal
gene having minimal ill effect on synthesis of beta peptide
chains.
 It may be completely asymptomatic.
 Prognosis is excellent.
3. Thalassemia intermedia
 Chronic hemolytic anemia caused by deficiency in a or B
chain synthesis.
 It may be present with persistent jaundice.
On the basis of defects in protein chain
a. Alpha thalassemia: gene related to alpha globin protein are
absent or mutated.
b. Beta thalassemia : gene defects affects on production of
beta globin protein
Clinical Features

Anemia (Before Diagnosis)

 Pallor
 Unexplained fever
 Poor feeding
 Enlarged spleen or liver
Progressive Anemia
 Signs of chronic hypoxia
 Headache
 Precordial and bone pain
 Decreased exercise tolerance
 Listlessness
 Anorexia
Other Features
 Small stature
 Delayed sexual maturation
 Bronzed, freckled complexion (if not receiving chelation
therapy)
Bone Changes (Older Children If Untreated)
 Enlarged head
 Prominent frontal and parietal bossing
 Prominent malar eminences
 Flat or depressed bridge of the nose
 Enlarged maxilla
 Protrusion of the lip and upper central incisors and eventual
malocclusion
 Generalized osteoporosis
Diagnosis

 Hematologic studies reveal the characteristic changes in RBCs

(e.g., microcytosis, hypochromia, anisocytosis, poikilocytosis,
target cells, and basophilic stippling of various stages).
 Low Hb and Hct levels are seen in severe anemia, although
they are typically lower than the reduction in RBC count
because of the proliferation of immature erythrocytes.
 Hb electrophoresis confirms the diagnosis and is helpful in
distinguishing the type of the thalassemia.
Contd.
 Radiologic findings include thinning of the cortex, widening
of the medulla (due to marrow hyperplasia) and coarsening of
trabeculations in the long bones, metacarpals and metatarsals .
 Skull shows the “hair-on-end” appearance due to vertical
striations from widening of the diploic space and atrophy of
the outer table of the skull
 Management
1. Repeat blood transfusion
Given at regular interval to maintain hb level at 10 – 11 mg/dl.
2. Iron chelating therapy
chelating agents capable of removing excess iron from the body has dramatically
increased life expectancy.
Desferrioxamine ( desferral ) is used to prevent complications of repeated blood
transfusions. Prolonged subcutaneous infusion with total dose of 40-60 mg/kg/day
is infused over 8-12 hours during the night for 5-6 days a week by a mechanical
pump.
3. Spleenectomy
4. Folic acid supplements
5. Bone marrow transplantation
6. Hep B vaccination to prevent transfusion related infection.
 SICKLE CELL ANEMIA

 Sickle cell anemia is an inherited autosomal recessive, lifelong

disease inherits two genes for sickle hemoglobin-one from each
parent.
 People who inherit a sickle hemoglobin gene from one parent and
a normal gene from the otherparent have a condition called sickle
cell trait.
 People who have sickle cell trait don't have thedisease but can
pass the sickle hemoglobin gene to their offspring.
 Sickle cell disease causes red blood cells to form into a
crescent shape, like a sickle.
 The sickle-shaped red blood cells break down easily,
causing anemia.
 Sickle red blood cells live only 10-20days instead of the
normal 120 days.
 The damaged sickle red blood cells also clump together
andstick to the walls of blood vessels, blocking blood flow.
 This can cause severe pain and permanent damage to the
brain, heart, lungs, kidneys, liver, bones and spleen.
 Severe pain in patient with sickle cell disease is an
emergency condition called sickle cell crisis.
 Sickle cell disease is most common in Africans and African-
Americans.
Etio-pathology
 Sickle cell disease is caused by a genetic abnormality in
the gene for hemoglobin, which results in the production
of sickle hemoglobin.
 When oxygen is released from sickle hemoglobin, it
sticks together and forms long rods, which damage and
change the shape of the red blood cell.
 The sickle red blood cell causes the symptoms of sickle
cell disease.
Clinical Features

 Progressive anemia
 Slight icterus
 Fever,headache,
 Arthritis
 Osteopathy of metacarpals and phalanges.
 Spleen is enlarged in the very young but shrinks as also ceases to
function (autosplenectomy) in subsequent years following
repeated thrombosis.
 Ulceration of skin overlying the lower limbs
 Nocturnal enuresis
 Growth retardation
 Folic acid deficiency

 The patient is particularly vulnerable to superadded bacterial

infections and anesthetic complications.

 A painful “crisis” may mimic a surgical abdominal

emergency, rheumatic fever or CNS infection.
 Poor red cell production together with rapid destruction may
lead to “aplastic crisis”.
 Diagnosis

 Peripheral blood smear test: presence of sickle shaped red cells

 Hemoglobin electrophoresis test: The diagnostic blood test is
called hemoglobin electrophoresis
 In high risk area for of sickle cell anemia, diagnosis can be made
prior to birth by amniocentesis and chorionic villus sampling.
Management
 Blood transfusion (common part of sickle cell anemia
management).
 Pain management by analgesic: severe pain is managed by
stronger pain medications
 Hydroxyurea (anticancer drug): used in sickle cell
management appears to reduce thefrequency of acute chest
syndrome and pain episodes.
 Antibiotic regimen (penicillin) is often started in children up
to age 5 in an effort to reduce the risk of potentially life-
threatening infections.
 Correction of acidosis.
 Folic acid and other vitamin supplementation.
 Other symptomatic and supportive care.
APLASTIC ANEMIA

 Bone marrow depression causing involvement of all the blood

elements is called aplastic anemia or simply pancytopenia.
 Involvement of only red cells is called the hypoplastic anemia
 Involvement of granulocytes is agranulocytosis, and
 Involvement of platelets is thrombocytopenia.
 Types
1.Congenital (constitutional) aplastic anemia may be:
• fanconi type (multiple congenital anomalies such as microcephaly
 Mental retardation
 Microphthalmia
 Squint, Nystagmus
 Short stature
 Hypogonadism
 Defects of thumb and radius
 Brown pigmentation of the skin
Contd.

 Dextrocardia and renal abnormalities.

 Schwachman diamond syndrome (pancreatic insufficiency)

2. Acquired aplastic anemia may result from viral, bacterial or

parasitic infections (HIV, HB, EBV)infiltration of marrow by
malignant tissue as in leukemia, osteopetrosis (marble bone
disease), irradiation, from chemicals and drugs such as
chloramphenicol, antimetabolites.
Diagnosis

 Definitive diagnosis is determined from bone marrow

examination, which demonstrates the conversion of red
bone marrow to yellow, fatty bone marrow.
 To make a diagnosis at least 2 of the following must be
present:
 Hb less than 100g/l
 Platelet less than 20,000/mm3, and
 absolute reticulocyte count less than 40,000/mm
Management
 Involves two main approaches:
(1) Immunosuppressive therapy (IST) to remove the presumed immunologic
functions that prolong aplasia or
(2) Replacement of the bone marrow through transplantation.
Blood transfusion
Antilymphocyte globulin (ALG) is the principal drug treatment used for AA.
Contd.
 For SAA and VSAA the treatment of choice is allogeneic bone marrow
transplantation (BMT). In the absence of BMT intensive immunotherapy is
used with anti-lymphocyte or anti-thymocyte globulin, cyclosporin with or
without prednisolone. Monotherapy with cyclosporin or
methylprednisolone are other options. Fanconi’s anemia responds to
androgen therapy.

 Till the time patients respond to therapy, control of anemia and bleeding is
required with transfusions of packed RBC or platelets. Infections need to
be
treated with appropriate antibiotics.