Dr M Kashif Ishaqi

Assistant Professor, PEDIATRICS

TAIBAH UNIVERSITY
To demonstrate knowledge of the process and stages of
Haematopoiesis.
To demonstrate basic knowledge of the structure and function
of Haematopoietic cells.
To be able to interpret Normal blood counts.
To demonstrate basic knowledge of pathophysiology, clinical
features and treatment outline of common diseases affecting
blood cells.
To be able to identify the Normal and abnormal blood cells.
Plasma-liquid
55%
Blood Cells-Formed elements
45%
Three types
Erythrocytes/RBCs
Leukocytes/WBCs
Granulocytes
Neutrophils
Eosinophils
Basophils
Agranulocytes
Lymphocytes
Monocytes

Thrombocytes/Platelets
3
 What is Hematopoiesis
Hematopoiesis is a term describing the formation and
development of blood cells.

Cells of the blood are constantly being lost or destroyed. Thus,

to maintain homeostasis, the system must have the capacity for
self renewal. This system involves:
Proliferation of progeny stem cells
Differentiation and maturation of the stem cells into the functional
cellular elements.

In the adult, all blood cell formation (red blood cells, white
blood cells and platelets) occurs in the Red Bone Marrow or
myeloid tissue.
Hemocytoblasts (hematopoietic stem cells)
All blood cells arise from hematopoietic stem
cell (HSC)
Hormones and growth factors push the cell
toward a specific pathway of blood cell
development
Hematopoiesis begins as early as the nineteenth
day after fertilization in the yolk sac of the embryo
Only erythrocytes are made
The RBCs contain unique fetal hemoglobins
At about 6 weeks of gestation, yolk sac production
of erythrocytes decreases and production of RBCs
in the human embryo itself begins.
At two months, the fetal liver becomes the chief site of blood cell
production.
Erythrocytes are produced
The beginnings of leukocyte and thrombocyte
production occurs
The spleen, kidney, thymus, and lymph nodes serve as minor sites of
blood cell production.
The lymph nodes will continue as an important site of lymphopoiesis
(production of lymphocytes) throughout life, but blood production in
the other areas decreases and finally ceases as the bone marrow
becomes the primary site of hematopoiesis at about 6 months of
gestation and continues throughout life.
When the bone marrow becomes the chief site of
hematopoiesis, leukocyte and thrombocyte
production become more prominent.
At birth, liver and spleen stop
hematopoietic activity.
Bone marrow now becomes active site
of hematopoiesis
Children up to teen years, has
hematopoiesis in all bones
Hematopoiesis gradually decreases in
shafts of long bones.
• In adults, red bone marrow is primarily
found in bones of the
– Axial skeleton
– Pelvic and pectoral girdles
– Proximal epiphyses of the humerus
and femur.
Medullary
Hematopoiesis in the bone marrow is called medullary
hematopoiesis

Extra medullary
Blood cell production in hematopoietic tissue other than
bone marrow
Liver
Spleen
Compensatory mechanism to provide blood cells in times of
need.
This can lead to hepatomegaly and/or splenomegaly
(increase in size of the liver and/or spleen because of
increased functions in the organs).
 • Red blood cells
–• carry oxygen via hemoglobin.

• Leukocytes/White Blood Cells make up the cells of the

immune system.
–• These cells help clear parasites, bacteria,tumors, debris, they
present antigens and activate other cells

Thrombocytes/Platelets
–•Must be present for clotting to occur
–• Involved in hemostasis
Size… Same size as the nucleus of a small
lymphocyte that is 7.2 um

Cell shape; round

Cytoplasm; Pink 7.2

Center pallor; Hemoglobin is mm
comparatively less in the center, showing
central pallor on dried film
1/3 size of the cell

Normal RBC, suspended in fluid is biconcave.

Transport oxygen from lungs to

tissues and carbon dioxide from
tissues to lungs
Dr M KASHIF ISHAQI
Composed of hemoglobin
Erythropoiesis O   O
2 2
= RBC production
Stimulated by hypoxia
Controlled by erythropoietin
Hormone synthesized in kidney
Hemolysis O   O
= destruction of RBCs 2 2

Releases bilirubin into blood stream oxyhaemoglobin

Normal lifespan of RBC = 120 days
Types
Neutrophils: Most common;
phagocytic cells destroy bacteria
(60%)
Eosinophils: Detoxify chemicals;
reduce inflammation (4%)
Basophils: Alergic reactions; Release
histamine, heparin increase inflam.
response (1%)
Lymphocytes: Immunity 2 types; b &
t Cell types. IgG-infection, IgM-
microbes, IgA-Resp & GI, IgE- Alergy,
IgD-immune response
Monocytes: Become macrophages
19-16
 Eosinophil Lymphocyte
Basophil

platelet

Neutrophil
Monocyte
Cell fragments pinched
off from
megakaryocytes in red
bone marrow
Important in
preventing blood loss
Platelet plugs
Promoting formation
and contraction of
clots

19-18
The changes caused by disease may be
detected by lab tests that measure
deviations of the blood constituents from
the normal values. These lab test may
include:
Type and crossmatch
Complete blood count
Red blood count
Hemoglobin measurement
Hematocrit measurement(packed cell
volume)
Mean corpuscular volume (MCV)
Mean corpuscular hemoglobin
concentration (MCHC)

White blood count

Differential white blood count
19-20
Platlet count
Hemoglobin electrophoresis
Radiologic Studies
CT/MRI of lymph tissues
Biopsies
Bone Marrow examination
Lymph node biopsies
RBC
Anemias–“lacking blood”
Polycythemia–“manyblood cells”
WBC
Leukopenia–low white blood cell count
• Leukemia–high white blood cell count
– Acute: quickly advancing; blast--‐type cells
– Chronic: slowly advancing; more mature cells
Platelets
Thrombocytopenia
Thrombocytosis
Erythrocytes/Red Blood Cells
Definition of Anaemia
Reduction of haemoglobin concentration or red blood cell (RBC)
volume below the range of normal values.

Means and ranges of normal haemoglobin varies with age and sex.

Anaemia is not a diagnosis, but sign of a disease which should be investigated.

Dr M KASHIF ISHAQI
 Normal Mean & Lower Limits of Normal Hb, HCT & MCV
AGE (YR) HEMOGLOBIN HEMATOC RIT (%) MCV (Μm3)
(G/DL)
MCV (fL): 70+ Age
(years)

Mean Lower Limit Mean Lower Limit

Mean Lower Limit

Newborn 16.8 14.0 55 45 119 110

0.5-1.9 12.5 11.0 37 33 77 70
2-4 12.5 11.0 38 34 79 73
5-7 13.0 11.5 39 35 81 75
8-11 13.5 12.0 40 36 83 76
12-14 female 13.5 12.0 41 36 85 78

12-14 male 14.0 12.5 43 37 84 77

15-17 female 14.0 12.0 41 36 87 79

What happens in anaemia?
 O2 carrying capacity of the blood

Increase cardiac output, augmented oxygen extraction and shunting of

blood flow towards vital organs and tissues.

Increased concentration of 2,3-diphosphoglycerate within RBC with

resultant right shift of the oxygen dissociation curve.

Few physiological disturbances occur until Hb < 80g/L.

Pallor only evident when Hb < 80g/L.

Younger children less symptoms and signs

Dr M KASHIF ISHAQI
Symptoms & signs of anaemia
Symptoms
Pallor
Lethargy & irritability
Decreased exercise tolerance/ shortness of breath
Dizziness
Signs
Pale mucous membrane & palmar creases
Tachycardia
Tachypnea
Flow murmur
Cardiac failure (severe anaemia)
Other signs related to underlying disease process

Dr M KASHIF ISHAQI
Classification of anaemia

Pathological classification
versus
Morphological classification

Dr M KASHIF ISHAQI
 Pathological classification

Substrate (Ineffective erythropoiesis)

production destruction

factory

Dr M KASHIF ISHAQI
Dr M KASHIF ISHAQI
Pathological classification

1. Inadequate production of RBC in the bone marrow

  RBC precursors in the bone marrow (red cell aplasia)

 e.g. Diamond Blackfan syndrome
 Aplastic Anemia

 Deficiency of specific factors

 e.g. iron, folate, B12 deficiency

Dr M KASHIF ISHAQI
Pathological classification

2. Increased destruction of RBC

Intrinsic abnormalities of RBC
e.g. hereditary spherocytosis, thalassaemia, sickle cell
anaemia
Immune mediated
e.g. autoimmune haemolytic anaemia, Rhesus or ABO
isoimmunization, drugs

Dr M KASHIF ISHAQI
Morphological classification

Based on mean corpuscular volume (MCV) = size of RBC

1. Microcytic anaemia (low MCV)

2. Normocytic anaemia (normal MCV)
3. Macrocytic anaemia (high MCV)

Dr M KASHIF ISHAQI
Normochromic Normocytic (normal MCV)

Causes

1. Acute blood loss

2. Transient erythroblastopaenia of childhood
(TEC)
3. Physiological anaemia of infancy
4. Haemolytic anaemia
5. Anaemia of chronic disease

Dr M KASHIF ISHAQI
Microcytic Hypochromic Anaemia

Inadequate haemoglobin formation

 Iron deficiency

 Thalassaemia

 Anaemia of chronic disease

 Sideroblastic anaemia

 Lead poisoning

Central pallor more than 1/3 of the red cell

Dr M KASHIF ISHAQI
Macrocytic Anaemia

Causes
1. Vitamin B12 deficiency
2. Folate deficiency
3. Diamond Blackfan Syndrome
4. Liver disease
5. Thyroid disease
6. Aplastic anaemia (pancytopaenia)
7. Fanconi anaemia (pancytopaenia)

Dr M KASHIF ISHAQI
 Anaemia Age, Prematurity
Sex: x-linked e.g G-6PD def
Diet: Iron? , early cow /goat milk, vegetarian
mother
Jaundice, pallor, Dark colored urine
Gallstones/Cholecystectomy, Trasfusion
Splenectomy, chronic illness, blood loss
History Drugs, Pica, Fava Bean
Family history

Laboratory Criteria

Physical examination CBC : HB

WCC
MCV
PLT
Polys
Pale
Yellow sclera Peripheral Smear
Visceromegaly, Lymphadenopathy Retics Count:
Signs of Nutritional deficiency Bilirubin:Unconjugated:
Congenital malformation Dr M KASHIF ISHAQI LDH, Haptoglobin
Urine DR
 Low Hb=Anemia
MCV

Low Normal High

microcytic normocytic macrocytic

Measure Ferritin Measure B12 + folate

Low Normal/high Normal Low

Megaloblastic
Anemia of anemia
Iron def
chronic disease/
Anemia
Congenital Hb dis.
Reticulocyte count

Hemolytic anemia or high low Anemia of chronic disease

blood loss Dr M KASHIF ISHAQI Renal failure
Marrow failure
 Hemolytic Anemia
Laboratory criteria:
History: Jaundice, Anemia, dark colored • CBC
urine • Reticulocytes
• Bilirubin
Physical examination: Pale, Yellow • LDH
sclera, Spleenomegaly • Haptoglobin

Positive Coombs Test Negative

Peripheral Blood Smear

Spherocytes Target/Sickle Cells Red Cell Other Abnormalities Normal

Or Elliptocytes Fragmentation

Dr M KASHIF ISHAQI
 Iron deficiency anaemia

• Inadequate dietary iron intake

– Most common from age 9 to 36 months.

– Diet history: early weaning from infant formula to cow’s milk, large
amount of cow’s milk, fussy eater, wouldn’t eat cereal or meat.

– Present with Hb as low as 40g/L & no symptoms.

– Unusual in the first 6 months: either breast fed or on iron-fortified

infant formula.

Dr M KASHIF ISHAQI
 Iron deficiency anaemia

• Iron studies
1. Ferritin 
• Ferritin – acute phase reactant
• Normal or high ferritin does not exclude iron
deficiency anaemia during an infection
2. Iron 
3. TIBC 

Dr M KASHIF ISHAQI
 Iron deficiency anaemia

• Management
– Dietary modification
– Iron replacement
• Elemental iron 6mg/kg/day
• Continued for 6- 8 weeks after Hb returns to normal

• Response to iron therapy

– 48 – 72hr reticulocytosis; peak at 5-7 days
– 4 – 30 days  Hb
– 1 – 3 mth repletion of iron stores

Dr M KASHIF ISHAQI
 Sickle Cell

Key features

• Red cells with pointed ends

• Crescent shape
• No central pallor
• Very dense hemoglobin

Dr M KASHIF ISHAQI
Thalassaemia
Thalassemia: spectrum of diseases characterized by
reduced or absent production of one or more globin chainsDisrupts the ratio of
alpha/beta production

 - thalassaemia
Defect in  globin chain synthesis
 - thalassaemia trait /  - thalassaemia major
Low MCV
•  - thalassaemia
Defect in  globin chain synthesis

Dr M KASHIF ISHAQI
Dr M KASHIF ISHAQI
White blood cells/WBC
Leukemia

Most common malignant neoplasms in childhood (41% of all malignancies in

children <15 yrs of age)

Leukemias: a group of malignant diseases in which genetic abnormalities in a

hematopoietic cell give rise to an unregulated clonal proliferation of cells.

These cells have a growth advantage over normal cellular elements, because of:
Proliferate uncontrolled
Fail to respond to normal growth inhibition mechanisms
Do not undergo apoptotic changes
Infiltrate normal organs
ALL Clinical Presentations
General Malaise, anorexia

Anemia Pallor, lethargy

Bone marrow
infiltration Neutropenia Infection

Thrombocytopenia Bruising, petechiae, nose bleeds

Bone pain

Hepatosplenomegaly
Reticulo-endothelial infiltration
Lymphadenopathy, superior mediastinal obsruction

CNS Headaches, vomiting,

Other organ convulsions, nerve palsies
Infitration *
Testes Testicular enlargement
* Rare at diagnosis, more often at relapse
THROMBOCYTES/PLATELETS
 THROMBOCYTOPENIA
DRUG INDUCED
BONE MARROW FAILURE
Viral Infections
Chemotherapy & Radiation Therapy
Infiltration of Abnormal Cells
 Aplastic Anemia
 Leukemia
 Metastatic Cancer

HYPERSPLENISM
Dr M KASHIF ISHAQI