The document discusses normal hematopoiesis and anemia. It begins by defining hematopoiesis as the formation of blood cellular components from hematopoietic stem cells in the bone marrow. It describes the three lineages of blood cells and the stages of hematopoiesis in embryo and postnatal life. The document then covers the clinical presentation, evaluation, classification, causes including nutritional deficiencies, and treatment of anemia. It provides details on iron deficiency anemia, including risk factors, etiology, and pathophysiology in infancy.

1. Dr. Salem F Gerbadi
Master Degree In Pediatrics

2. Normal Hematopoiesis
 Is the formation of blood cellular
components.
 All cellular blood components are derived
from haematopoietic stem cells (HSCs) .
 HSCs are primitive stem cells have the
unique ability to give rise to all of the
different mature blood cell types .

3. NORMAL HEMATOPOIESIS
In Embryo Life
 (before 16 days gestation) do not have
blood.
 Intrauterine hematopoesis passes into 3
stages:-
 1st 8 weeks → in yolk sac
8th week - 6th month → in the liver
 after 6th month → in bone marrow

4. NORMAL HEMATOPOIESIS
 At Birth &Infancy: it takes places in
bone marrow of all bones.
 During Childhood: it takes place only in
red bone marrow in flat bones only (ends
of long bones (femur & tibia), , skull,
sternum and ribs).
 the inactive yellow marrow in the long
bones can restore its activity in case of
excessive hematopoietic needs.

5. All blood cells are divided into three
lineages.
1. Erythroid
 Are the oxygen carrying .
 Both reticulocytes and
erythrocytes (functional )are
released into the blood.
Erythropoies
is

7. HORMONAL CONTROL OF
ERYTHROPOIESIS
 Erythropoietin (EPO) release by the liver & kidneys is
triggered by:
 Enhanced erythropoiesis increases the RBC
count in circulating blood & Oxygen carrying
ability of the blood
Hypoxia &
anamia

8.  Thyroid hormones, thyroid-
stimulating hormone
 Adrenal cortical steroids,
adrenocorticotrophic hormone
 Human growth hormone (HGH)
All promote erythropoietin formation
(erythropoiesis)

9. 2. Lymphocytes
 Are the cornerstone of the adaptive
immune system. They are derived from
common lymphoid progenitors.
 The lymphoid lineage is primarily
composed of T-cells and B-cells .
Lymphopoiesis

10. 3. Myelocytes
 which include granulocytes,
megakaryocytes and macrophages.
 Are derived from common myeloid
progenitors
 Involved in such diverse roles as
innate immunity, adaptive immunity,
and blood clotting.
Myelopoiesi
s

11.  Decreased life span of neonatal RBCs
within the circulation (60-90 days)
 In prematur, e remarkably shorter
RBCs life span (35-50 days)
 In children = 100- 120 days (adult)

12.  Hb molecule is composed of Heme
groups (ferrous iron containing) attached
to 4 polypeptide chains which define the
type of Hb.
Types
Fetal Hb (Hb F) → containing (α2 , ɣ2) chains , has
high affinity to 02.
Adult Hb → HB A (α2 & β2) , HB A2 (α2 & Δ2)

13. *At the 3 – 6 month after birth→ normal switch from ɣ to β
chain occurs
At 6 months
At birth
Intrauterine
Hb type
> 0.5 %
70 %
Dominant
Hb F
97%
30%
---
Hb A
2.5%
Trace
---
Hb A2

14. 1. Hemoglobin content:
 In 1st 2 weeks = 14 - 20 gm/dl.
 In Infancy = 10 - 14 gm/dl.
2. RBCs count:
 In newborn→ 6 million/mm3.
 Afterwards → 4 - 6 million/mm3.

15. 3. Hematocrite value (Ht)
 Packed red cell volume = percent
of RBCs volume in 100 ml blood →
33 -44%.
4. Mean corpuscular volume (MCV)
 The average volume of a red blood
corpuscle.
If < 80 = RBCs are small (Microcytes).
If > 94 =RBCs are big (Macrocytes)

16. 5. Mean corpuscular hemoglobin (MCH)
 Refers to the average quantity of hemoglobin
present in a single red blood cell.
 Range = 27- 32 pg.
 If < 27 pg → RBCs are hypochromic.
6. Mean corpuscular hemoglobin concentration
(MCHC)
 The average amount of hemoglobin in a group of red
blood cells. Range → 32-36 g/dL.

17. 7. Reticulocytic count = account 1 %.
Reticulocytosis occur in:
 Hemolytic anemias.
 Hemorrhage
 Response to hematinics e.g. (iron, folic
acid, B12)
 Recovery of bone marrow from
suppression.
8. Platelet count= 150.000 - 400.000 /mm3

18. ANEMIA

19. DEFINITION
 Anemia is defined as a condition
where the hemoglobin conc. or
hematocrit (packed red cell volume) of
an individual is lower than the level
considered normal for the person’s
age and sex.

20. Age (yrs) Hb <g/dl Hct % RBCs Reticulocytes
%
Cord
blood
13.7 - 20 55 5.3 5
2ws –
3ms
11.5 - 13 35 4.3 1
6ms to 5
yrs
11.5 - 13 36 4.7 1
6 to 14
yrs
12 - 14 39 5 1

21. Prevalence Of Anemia
*40% In Children Aged 6ms -5yrs (269 Million Children With
Anemia)
Developed
nations
Developing
nations
Age group
17 %
42 %
Pre School Children
%
9
%
53
School children

22. Anemia Grades
*Who Classification Of Anemia 2021 In Pediatrics (NATIONAL FAMILY
HEALTH SURVEY)
Hb g/dl
Grade
10.9 – 10
Mild
9.9 – 7
Moderate
< 7
Severe

23. Causes Of Anemia
(Classification!!!)
Anemia from inadequate production.
Anemia due to  destruction (hemolytic)
Anemia of blood loss (post-hemorrhagic).
3.

24. Causes Of Anemia
 Decreased production
Specific factor
defeciency
(Dyshemopiotic anemia)
Decreased production despite
normal RBCs precursors)
Decreased erythroid cells in
bone marrow (Bone marrow
failure)
 Iron deficiency
 Folic acid &
B12 deficiency
 Protein
deficiency.
Anemia of chronic
disease:
- Chronic inflammation.
- Chronic infection
- Chronic renal failure.
 Pure red cell anemia.
 Aplastic anemia
 Marrow infiltration
e.g.: Leukemia ,
Myelofibrosis

25. Causes Cont…
Anemia due to increased destruction
(Hemolytic) :
Extra-corpuscular causes:
 Immune:
- Iso-immune: Rh and ABO incompatibility
- Auto-immune: idiopathic or 2ry (e.g. SLE)
 Non immune: - March hemoglobinuria
- Paroxysmal nocturnal hemoglobinuria
- Infections (malaria, toxoplasmosis, septicemia)
- Toxic: snake venom, industrial toxins
- Mechanical: burns, prosthetic cardiac valve
 Hypersplenism
Corpuscular causes:
 RBC membrane: hereditary
spherocytosis, elliptocytosis,
etc.
 RBC enzymes: G6PD
deficiency, pyruvate kinase
deficiency.
 Hemoglobin: -
 Qualitative: sickle cell
disease, Hb C, D, etc
 Quantitative: thalassemias

26. Causes Cont…
 Anemia from blood loss ( post-hemorrhagic):
Acute post-hemorrhagic anemia after overt
bleeding
 Chronic post-hemorrhagic anemia (occult
bleeding-iron deficiency). e.g. due to Ancylostoma
orcow's milk allergy)

27. Classification
 Clinical
findings
 Acute / Chronic
 Hereditary /
Acquired
 Red cell size
 Determined by MCV
 Red cell
kinetics
 Determined by
reticulocyte count

28. Classification
According to MCV ( 76 – 96 femtolitre)
 Normocytic:
 Anemia of chronic disease
 Bone marrow failure / aplasia/
hypoplasia
 Renal failure
 HIV infection
 Microcytic:
 Fe deficiency
 Thalassemia
 Congenital sideroblastic anaemia

29.  Macrocytic:
 B12 or folate deficiency
 Hypothyroidism
 Chronic liver disease
 Down syndrome
 Marrow failure
 Alcohol

31. Clinical Presentation
1. Common manifestations: Pallor,, exercise
intolerance, dyspnoea, palpitations, headache,
lack of conc., loss of appetite, irritability, excessive
sleeping, syncope, hemic murmurs.
1. Less commonly: anorexia, nausea, flatulence,
constipation, mild proteinuria, fever
2. Severe cases:  C.O, CHF

32. 3. Manifestations of etiology :
 Hge, occult blood
 Growth failure: Chronic Dis.
 Acute hemolysis: beans, dark urine
 Chr. Hemolysis → jaundice, skeletal changes,
organomegally
 Acute hemolysis: beans, dark urine
 Veno-occlusive crisis: SCA
 Iron def.: PEM, nail, glossitis
 Neurologic signs: ataxia, + ve Babinski: PA
 Short stature, sk., cardiac, renal :Aplastic

33. Clinical Evaluation
A. History
1. Symptoms of anaemia: lethargy, shortness of
breath on exertion.
2. Age: Iron deficiency anaemia, Neonatal anaemia
3. Sex: G6PD.
4. Race: Sickle cell anaemia
5. Family history: G6PD deficiency, sickle cell,
Fanconi anaemia, spherocytosis, family member
with early cholecystectomy or splenectomy,
ethnicity, race.

34. .
1. Nutrition: cow’s milk, strict vegetarian, goat’s
milk, pica, cholestasis, malabsorption.
2. Overt blood loss: epistaxis, haematemesis,
haematuria, blood in stools.
3. Drugs: cytotoxics, antibiotics, antimalarial,
anticonvulsants, NSAIDs
4. Diarrhea: malabsorption of Vit.B12 or E or
iron, inflammatory bowel disease, milk protein
intolerance, intestinal resection
5. Infection: giardia, fish tapeworm, mycoplasma,
HIV, malaria, blind loop, EBV, CMV,
parvovirus, endocarditis, hepatitis

35. B. Examination
1. Skin:Pigmentation, Petechiae
2. Head:FrontalBossing, Microcephaly, HairChanges
3. Eyes:Retinopathy, BlueSclera, Kayser-fleischerRings
4. Ears:Deafness
5. Mouth:Glossitis, AngularStomatitis, GumBleeding
6. Chest:WidespreadNipples, Murmur
7. Abdomen:Organomegaly, AbsentKindney
8. Extremities:SpoonNails, MeesLines, AbsentThumbs
9. Rectal:Haemorrhoids, HemePositiveStools
10. Nerves:Irritability, Apathy, Dementia ,Ataxia, P.Neuropathy
11. General:SmallStature

39. Laboratory Investigations
1. General
Hb , Hct
RBCs count, WBCs, Platelets
Blood Indices
Reticulocytes
Cell morphology (PBF, bone
marrow aspiration)

40. 2. Specific
 S. iron
 T.IB.C
 S. ferritin
 S. Bilirubin
 Coomb’s test
 Fragility test
 Schilling’s test
 electrophoresi
s
 G6PD levels

41. Treatment
According To The
Cause

42.  Resuscitation
 Treat underlying disease
 Stop ongoing losses
 IV fluids
 Analgesia
 Iron therapy
 Dietary evaluation
 Blood transfusions
 Drugs eg. Corticosteroids, antibiotics,
immunosuppression.
 Vit.B12 / Folate
 Splenectomy
 Bone marrow transplant

43. NUTRITIONAL ANEMIA

44. Iron Deficiency Anemia
(IDA)
Megaloblastic Anemia

45. IDA
 Due to deficiency of specific nutrients (iron)
 Most common nutritional deficiency in
children and is worldwide. WHY???
 Prevalence : it is estimated that roughly 5%
of the world population
 Highest :
 6 - 24 months
 Artificially fed infants.
 low socioeconomic status.

46. Physiology
 Storage Iron :
 Newborn→ about 0.5 gm of iron.
 Child → 70 mg/kg
 Iron stores are built up in the last trimester of
pregnancy.
 Sufficient for 4 ms of term newborn
 Preterm and low birth wt. infants are associated with
decreased Fe stores.
 The transport and storage of iron is largely mediated
by 3 proteins:
 Transferrin
 Transferrin receptor (TR)
 Ferritin

47. Normal Daily Requirements Of Iron
 Term breast fed: starting from 4 ms.
 PT & Formula fed: from 1 - 2 months.
 1 mg/kg/day elemental iron for normal
infants and children (max 15 mg/day).
 2 mg/kg/day elemental iron: LBW,very low
Hb

48. Dietary Iron
I. Heme iron compounds (hemoglobin and
myoglobin) :
 High bioavailability (20‐30%)
 Foods of animal origin: 1.5 - 6 mg iron /100 g
meat, liver, poultry, fish, etc.
 Easily digested and readily absorbed.
 Absorption is not affected by diet.

49. II. Non-heme iron ( ferric iron salts ) :
 Poor bio availability (2‐5%)
 Egg yolk, green vegetables, whole grains,
legumes, nuts ( + 1.5 mg/100 g). ferric 
ferrous before absorption.
 Absorption (50% : breast milk , 10% of
cow’s milk iron

50. Iron Absorption
Absorption Promoters
(40%↑↑)
 Ascorbic acid
 Amino acids (meat,
fish)
 HCl
 Fermentation
(probiotic)
Absorption Inhibitors
 Phytates (Cereals)
 Tannin (Tea, coffee)
 ↑ phosphates (in
bread, cow milk and egg
yolk)
 Soy protein

51. Functions Of Iron
Critical element in function of
cells
Hb facilitates O2 transfer to
tissues
Myoglobin transfer O2 to
muscle cells

52. Risk Factors In Infancy
Maternal iron deficiency
Breastfeeding beyond 6 ms without
complementary food
Complementary food low in iron or
poorly bioavailable.

53. Etiology of IDA
Inadequate iron stores at
birth:
 Premature.
 Multiple births.
 Severe maternal iron def.
 Fetal blood loss.
Impaired absorption of iron:
chronic diarrhea and celiac
disease.
Blood loss during infancy:
 Cow milk allergy.
 Acute or chronic
hemorrhages.
 Parasitic infestations as
hook worms.
Inadequate dietary intake
 Early cow milk.
 Exclusive breast feeding
after 6 months.
 Low intake
Failure to meet increased
demands for growth:
 premature.
 adolescence.

54. Stages Of The Development Of Iron Deficiency
Prelatent
Reduction in iron stores without reduced serum iron levels
Hb (N), MCV (N), iron absorption (), transferin saturation
(N), serum ferritin (), marrow iron ()
Latent
Iron stores are exhausted, but the blood haemoglobin level
remains normal
Hb (N), MCV (N), TIBC (), serum ferritin (), transferin
saturation (), marrow iron (absent)
Irondeficiencyanemia
Blood haemoglobin concentration falls below the lower limit
of normal
Hb (), MCV (), TIBC (), serum ferritin (), transferin
saturation (), marrow iron (absent)

55. Clinical manifestations
1. General manifestations of anemia
2. particular findings of effect of iron def. on
systems:
GIT: Anorexia, atrophic glossitis, dysphagia, Pica
(ingestion of wall plaster, clay), Geophagia (earth),
Pagophagia (ice), malabs.lactose int.
CNS: Short attention span, irritability, breath holding,
↓ alertness, ↓ learning ability and school performance.

56. Immunological:
URTI common but bact. infections↓.
Spleen slightly enlarged in 15%
Growth retardation and signs of other deficiencies
CVS:  HR , cardiac hypertrophy
Plasma volume
Musculoskeletal System:
Impaired performance
Rapid lactic acidosis
Physical signs
 pallor, hemic murmur
 tongue: pallor, bald & shining tongue, loss of
 papillae
 angular stomatitis
 Nails: platynychia, koilonychia
.

57. Laboratory findings
.
↓↓
Serum Iron Concentration
↑↑
Total Iron-binding Capacity
↓↓
Saturation Of Transferrin
↓↓
Serum Ferritin Levels
↑↑
Serum Transferrin Receptors

58.  Hypochromic Microcytic Anemia, Anisocytosis (variation
in size) & Poikilocytosis (variation in shape).

59. Treatment Of IDA
 Hb below 5 g/dl: Risk of cardiac failure; Hospitalization is
desirable.
 If Hb is below 3 g/dl (< 4 g/dl with infection and in young
children): Blood transfusion is usually required; packed red cell
transfusion 2‐3 ml/kg at one time.
 For treatment dose of oral iron is 3 - 6 mg/kg/day; ferrous
sulphate, gluconate and fumarate are most commonly used and
cost effective. Newer iron compounds like ferrous glycine
sulphate, carbonyl iron are costly and have not been studied
adequately in children

60. Oral Iron Therapy
 Dose: 3‐6 mg/kg of elemental iron
 Divided in 1‐2 doses
 On empty stomach –ideal
 On full stomach if intolerance
 Duration : 3 ms after Hb has
normalized

61. Oral Iron Side Effects
 Nausea, vomiting, pain in abdomen,
diarrhea, constipation in about 14%
cases
 Discoloration of stool
 Staining of tongue / teeth
 True intolerance rare

62. Response To Iron Therapy
 24‐48 hrs Erythroid hyperplasia
 Reticulocytosis 48 - 72 hrs, peak: 5th - 10th d.
 ↑ Hb after 4-30 days ( 0.25 - 0.4 g / dl/ day).
 ↑ hematocrit (1 % / day).
 Repletion of Iron stores in 1 - 3 ms.

63. Non Responders To Iron Therapy
 Wrong formulation and dosage
 Poor compliance
 Basic cause not treated esp. bleeding
 Thalassemia
 Red cell aplasia

64. Treatment cont…
 Parenteral iron therapy: Iron dextran mixture
(Imferon) 50 mg elemental iron / ml: only in
intolerance or malabsorption or severe GIT
disease.
 Blood transfusion: Severely anemic children
with Hb < 4 g/dl given packed RBCs
 Partial exchange transfusion: surgical
emergency, CHF
 Treatment of etiology correct diet and
Ancylostoma.

65. Acute Iron Intoxication
 Accidental ingestion of large doses of iron:
mortality rate 50%.
 Early symptoms : Vomiting, diarrhea, dehydration,
corrosive iron on stomach,intestines.
 Later : Severe irreversible CV collapse, shock, coma.
marked in plasma iron.
 Treatment: Forced vomiting & gastric lavage with
sodium bicarbonate.
 Desferrioxamine (Desferal) specific chelator of iron
(antidote).
 Blood and plasma transfusion, oxygen, and electrolyte
correction.

66. Megaloblastic Anemia

67. Definition
Anemiawith megaloblasts in BM
and macrocytes (Hypersegmented
neutrophils) in peripheral blood.
 All blood components may affected
 Common in infancy…why ???

68. Causes
1- Inadequate intake of folic acid:
 Feeding on goat’s milk (very poor in folic acid).
 Feeding on heat-sterilized cow’s milk <50% folic acid.
2- Relative deficiency :
 Rapid growth : prematures.
 Chronic hemolytic anemias, leukemias, lymphomas.
3- Defective absorption:
 Chronic diarrhea.
 Prolonged antibiotics , antiepileptics (phenytoin, phenobarb.).
 Malabsorption syndromes, congenital folate malabsorption
syndrome.
 Folic antagonists: Co-trimoxazole, methotrexate, pyrimethamine .
 Ascorbic acid deficiency

69. Clinical Pictutre
Early few weeks after birth (pure vegan mother)
Anemia (Anorexia, pallor, ........ )with slight jaundice.
GIT manifestations :
 Red glazed tongue & glossitis.
 Abdominal pain and chronic diarrhea.
Neurologic manifestations:
-May occur Only with vitamin B12 deficiency:
 Posterior column degeneration → sensory ataxia
 Pyramidal tract degeneration → delayed motor milestones
 Peripheral Nerve degeneration→paraesthesia.
 Hyper‐pigmentation of knuckles/ terminal phalange

71. Laboratory Investigations
 Peripheral blood:
  Hemoglobin (< 6 g/dl).
  MCV to 100 fl (macrocytosis).
  reticulocytic count.
 Neutropenia + hypersegmented nuclei
of mature polymorphs.
 Mild thrombocytopenia.
 Serum & RBC folate ↓↓
 Bone marrow :
 Hypercellular with predominant
megaloblasts.

72. The Schilling test
 Is used to determine whether the body absorbs vitamin
B12 normally.
 Two doses of vitamin B12 (cobalamin). The first dose
is radioactive and taken by mouth. The second dose is
not radioactive and is given as a shot 2 - 6 hours later
to saturate transcobolamin.
 Urine will then be collected over the next 24 hours to
measure whether vitamin B12 was absorbed normally
or not.
 Normal Values:
-Urinating 8 - 40% of the radioactive vitamin B12 within
24 hours is normal.

73. Treatment
1. Folic acid deficiency:
- Folic acid tablet 0.5 - 1 mg/day for 3-4 weeks.
- If diagnosis of folic acid deficiency is doubtful use smaller
dose 0.1 mg/day for a week & look for reticulcytosis
(therapeutic test).
(large dose of folic acid worsen neurologic manifestation of
vitamin B12 deficiency)
2. Vitamin B 1 2 deficiency:
1- Without SCD: B12 1 mg IM monthly for life.
2- With SCD: B12 1mg IM daily for 2 weeks then 1 mg IM
monthly for life.
* With successful treatment; reticulocytosis is seen in 2- 4 days.