Anemia of Inadequate

production

Anaemia
Hemoglobin level below the normal
range for the age and sex
Neonate < 14 gr/dl
1-12 months < 10 gr/dl
1-12 years < 11 gr/dl
Hemoglobin at birth cord blood = 16-18 gr/dl
24-48 hour of age Increase due to hemoconcentration
3 months of age - Drop up to 9.5 11 gr/dl

Causes of Anaemia
Impaired red cell production

Approach to Common Causes of Anemia in Children

Dysmorphic

Microcytic

Iron Deficiency Anemia

Iron Metabolism
Etiology
Clinical manifestations
Laboratory investigations
Differential Diagnosis
Treatment

Iron Metabolism
Total body iron content
New born baby 250 mg ( nelson -0.5 gr )
Adult - 4- 5 gr

Iron requirement
To fulfill the deficit - 4.5 gr over 15 years
4.5 gr/365 = 0.8 mg/day

To replace Iron loss via epithelial shedding

Total elemental iron requirement = 1 mg/kg/d
Iron requirement
One year old infant = 8mg/day
Father = 9 mg/day
Mother =15 mg/day

Iron intake
Breast milk 1.5 mg/L 50% absorbed
Infant formula 5-9 (7-12) mg/L 10% absorbed
Preterm formula - 15mg/l for b.wt < 1800 gr

Cows milk 0.5 mg/L 10% absorbed

Mixed diet 4-9 mg/day 10-15% absorbed
Interfered by food tea (tanin), Caws milk (calcium),
High fiber foods ( phytate)
Iron from cereals only 1% is absorbed

Facilitated by Breast milk, vitamin C

Iron supplementation
After 4 months for exclusively breast fed babies

Iron Deficiency and Anemia

US
1-2 years 9% deficient 3 % anemic
(nelson)

Adolescent - 9% iron deficient 2%

anemic(nelson)
Prevalence of iron deficiency - 18% whites and 33%
immigrants (illustrated)

Sri Lanka
30-40 % anemic
Iron Deficiency ?

Etiology
Inadequate intake

( iron reclaimed by drop in Hb in 2-3mo)

Early - LBW or unusual blood loss at birth

9-24 mo- Term babies

Absorption
Interfered by cows milk,
Facilitated by Vit C

Blood loss
GIT polyp, hemangioma, inflammatory bowel disease,
Hookworm, Chronic diarrhea, cows milk protein allergy
Blood loss due to heat labile protein in cows milk
Blunting of villi due to iron deficiency can lead to loss of iron
Intense exercise conditioning in girls

Clinical Manifestations
Pallor
Irritability & behavioral problems
Impaired neurological and
intellectual functions ( girls with Serum ferritin level less
than 12 ng/l improved after 8 weeks of iron)

Pagophagia
Cardiac tachycardia, cardiomegaly, systolic
murmur
Breath holding attacks are reduced by iron
Iron is found
in Monoamine oxydase, cytochromes , catalase and peroxidase
therapy

Laboratory Findings in iron

deficiency

Serum ferritin
Serum iron
Iron binding capacity
Transferin saturation
Free Erythrocyte protoporphyrine ( EFP)
MCV & MCH
(Microcytic, Hypo chromic)
Blood picture Phoikilocytosis, Nucleated
RBC
Reticulocyte ( relative )
Thrombocytosis ( similarity of erythropoietin &
Thrombopoitin)

Deferential Diagnosis
Hypo Chromic Microcytic Anemia
Thalasaemia trait ( beta, alpha, E)
RBC count raised in thal trait, not in iron deficiency
RDW is wide in iron deficiency

Anemic of chronic disease( usually Normocytic but can be Microcytic)

Lead poisoning
Other Microcytic anemia
Sideroblastic anemia (

dimorphic and high RDW, serum iron increased,

transferring saturation increased and ring sideroblasts in the marrow

Congenital sideroblastic anemia ( X linked with

lionization)

Atransferinemia; congenital absence of iron binding

protein ( treated with apo-transferrin)

Treatment
Regular response to iron!
Simple iron salts can be used

( sulphate,

gluconate,fumarate)

Sodium iron editate and polysacharide iron

complex does not stain teeth

Dose 4-6 mg/kg of elemental iron in three

doses
only 20% of ferrous sulphate is elemental iron

Duration
3 months
8 weeks after blood value come to normal

Treatment ct.
Intolerance to iron is uncommon in young
children than adolacents and adult
Consumption of milk should be reduced
Expected rate of Hb rise 1 gr/dl/week (0.5
mg/dl/day)

Blood transfusion not necessary and can

be dangerous due to hypervolemia and
cardiac dilatation.
Hb value less than 4 gr/dl should get only
4ml/kg of packed cells at a time.

Response to iron therapy in iron

deficiency anemia
Time after
Response
iron
administra
tion
12=24
Replacement of intracellular
hours
iron, subjective improvement;
decreased irritability,
increased appetite
36-48 hours Initial bone marrow response ;
erythroid hyperplasia
48-72 hours Reticulocytosis, peaking at 5-7

Megaloblastic Anemias
1. Ineffective erythropoiesis Active
erythropoiesis with premature death of cells
2. High MCV and hyper segmented WBC
3. Deficiency of B12 or folate and rare
metabolic disorders

Folate deficiency
Folate abundant in green vegetable
and animal food heat
labile( polyglutamate)
Polyglutamate monoglutamate by
folate conjugase in entire intestinal
brush border
Folic acid Tetrahydrofolate
( biologicaly active form) by Tetra
Hydro Folate reductatse enzyme
Body stores are limited Anemia in

Clinical features
Neonate and infant
Common in Very low birth weight babies
routine supplementation
Peak incidence 4-7 mo ( earlier than iron
deficiency)
Signs and symptoms related to anemia
Irritable, fail to gain weight, chronic diarrhea
Thrombocytopenia and Hemorrhage

Older children
Signs and symptoms related to anemia

Etiology
Inadequate intake
Decreased absorption
Congenital abnormalities in folate
metabolism
Drug induce abnormalities of folate
metabolism

Etiology
Inadequate intake
Increased demand ( pregnancy, infancy, hemolysis)
Aggravate by infections

Decreased absorption
Chronic diarrhea and other bowel disease
Antiepileptic drugs ( Phenytoin, primidone,
Phenobarbital)

Congenital abnormalities in folate metabolism

Treated with high doses of folate

Drug induce abnormalities of folate metabolism

MTX, Trimethoprim, Pyrimethmine

Laboratory findings in Folic acid

Deficiency

Macrocytic MCV > 100 fl

Reticulocyte count low
Neucleated RBC
Neutropenia and thrombocytopenia
Reduced RBC folate level ( normal 150600 ng/ml)
Bone marrow hypercelluler

Treatment
Folic acid 0.5 -1 mg/day
High doses may correct B12
deficiency anemia also. Therefore If
the diagnosis is in doubt ; trial of folic
acid 0.1 mg/day for one week and
see the response
Duration of treatment 3-4 week

Vitamin B- 12 Deficiency

Vitamin B12 ( Cobalamin) deficiency

Cobalamin - produced by micro-organisms

Stomach Combine with R protein and IF
Duodenum Break down R protein by pancreatic enzymes
Ileum ( distal) absorption
Plasma Bind to trans Cobalamin II and
transported to liver, bone marrow,
Cells Receptor mediated endocytosis and converted to
methylcobalomin and adenosyl cobolamin ; Transfer of methyl
groups to DNA

Etiology of B12 Deficiency

Inadequate Intake
Lack of intrinsic factor
Impaired Vitamin b12 absorption
Absence of Vitamin B12 transport
protien

Etiology of B12 Deficiency

Inadequate Intake
Stores sufficient for 3-4 years ( neonates 4-5 mo)
Strict vegetarians and their babies

Lack of intrinsic factor

Congenital Pernicious anemia
Juvenile pernicious anemia
Gastric surgery

Impaired Vitamin b12 absorption

Intestinal pathologies or resections ( NEC, IBD)
Bacterial overgrowth or tapeworm

Absence of Vitamin B12 transport protein

TC II deficiency ( normal B12 level due to TCI and TCIII)

Clinical features of B12

Deficiency
General Weakness, fatigue, Failure
to thrive, irritability, pallor, glossitis,
Vomiting, diarrhea, icturus.
Neurologic Paresthesia, sensory
deficit, Hypotonia, seizures,
development delay, regression,
neuropsychiatric changes
Hyporeflexia babinski responses and
clonus

Laboratory findings in B12

Deficiency
Identical with folate deficiency
Serum B12 levels below 100 pg/ml
Increased levels of methylmelonic acid in urine
( normal 0- 3.5 mg/24 hr)
Schilling test C57 labeled B 12 Orally
High dose ( flushing dose) of B12 Paretaral 2 hrs later
Normal 10-30% C57 labeled B 12 excretion in urine
IF deficiency <2% excretion but corrected by IF
Intestinal pathology Not corrected by IF

Treatment of B12 deficiency

Parenteral B12 (1 mg)
Response in 2-4 days
Neurological deficiencies IM doses
daily for 2 weeks
Maintenance Monthly 1 mg IM for
life

Other Megaloblastic Anemia

Oroticaciduria
Thiamine-Responsive Megaloblastic
Anemia
Deficiency of adenosyl Cobalamin
and methyl Cobalamin

Physiologic Anemia of
Infancy

Physiologic Anemia of
Infancy
At birth Hb 18-20 gr/dl
At 8-12 wk Hb - 9-11gr/dl (Physiologic anemia)
Reasons for physiologic anemia
Increase of availability of oxygen saturation from
fetus to new born from 50% to 95%
Change the type of Hb ( HbF HbA)
Down regulation of erthropoitin production
Erythropoiesis is suppressed

Iron is recycled and sufficient up to 20 wks

with no intake

Physiologic Anemia of Premature Infants

More rapid and extreme drop of Hb 7-9
gr/dl by 3-6 weeks ( may be lower in Very premature
babies)

Causes for anemia of premature infants

Blood loss due to Sampling
Suboptimal erythropoietin response
( hepatic Renal occur around 40
weeks )
Short survival of RBC 40-60 days Vs 120
days
Rapid growth
Slow ongoing hemolysis

Physiologic Anemia of Premature Infants

Treatment on the clinical condition

( can tolerate up to 6.5gr/dl)
Folic acid and iron ( 4-6 mg/kg/d)
Blood transfusion 10-15 ml/kg
Erythropoietin ?

Prevention
Minimize blood loss by sampling

5 ml from a 800 gr baby = 500 ml from a 80 kg (80

000 gr) man

Causes of Anaemia
Impaired red cell production

ther Causes - Anemia of inadequate productio

ed cell aplasia
Diamond-Blackfan Anemia
Transient Erythroblastopenia of
childhood (TEC)
Parvovirus B19 infection
Anemia of Chronic Disorder (ACD) &
ARF
Congenital Diserythropoietic Anemia
(CDA)

Definition for Severe Aplastic

Anaemia
Two or more of the following cell line
are compromised in a patient with
moderate or severely hypo cellular
bone marrow
Absolute neutrophil count less than
500/mm3
A Platelet count less than 20 000/mm3
A reticulocyte count less than 1% after
correction for the hematocrit

Aplastic Anaemia
Reduction of all three cell lines Pancytopenia
RBC Anaemia
Platelets Thrombocytopenia
White cells leucopenia

Causes of Aplastic anaemia

Inherited
Infections hepatitis
Drugs Sulphonamides, chemotheraphy
Toxins Benzene, glue

Acquired Fanconi anaemia

Idiopathic

Fanconi Anemia

Fanconi Anaemia Clinical

features
Most comment inherited anaemia
Autosomal recessive inheritance
Associated with congenital abnormalities
Short stature
Abnormal radii and thumb
Renal malformations
Micropthalmia
Pigmented skin lesions
Signs of bone marrow failure usually appears at 5-6 yrs of
age

Fanconi anaemia
Diagnosis
Neonates with Fanconi nearly always
has normal blood counts
Increased chromosomal breakage of
peripheral blood cells
Death due to aplastic anaemia or
leukemia
Treatment Bone marrow transplant
from unaffected siblings

Schwaman- Diamond
syndrome
Rare
Autosomal recessive
Clinical features
Aplastic anaemia
Pancreatic exocrine failure
Skeletal abnormalities

Risk of acute leukemia

Transient Erythroblastopenia of Child

hood - TEC

The most common acquired red cell

aplasia
Commoner than congenital red cell
aplasia
6 months to 3 years of age ( most
above 1 yr)
Transient immunologic suppression
of erythropoiesis may follow viral
infections but not Parvovirus B19
Neutropenia in 20%

Transient Erythroblastopenia of Child

hood - TEC

MCV normal
HbF Not present
Red Cell ADA levels Normal ( high
in other congenital aplastic Anemias)
Recover within 1-2 months
Transfusions may be required ( usually
only one)

Acquired Pancytopenias

Acquired Pancytopenias
Drugs and chemicals

Acquired Pancytopenias

Radiation
Immune diseases
Pregnancy
Paroxysmal Nocturnal
Hemoglobinuria

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