HEMATOPOIESIS

Fery Soedewo,dr,MS,SpPK(K)
2011

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 HEMATOPOIESIS

 All blood cells are derived from a common

precursor Pluripotent Stem Cells and after
mitotic division , one of the daughter cells
retain the property of Pluript.SC while the other
is committed to produce mature blood cells

 This committed SC later differentiate into a blast

cell in one of the cell lines (Differentiation
phase)

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 The development of blood cells from the blast
cell stage progresses through 3 further phases :

- Proliferation
- Maturation
→ Release into the circulation

Stem Cells are found within the bone marrow

and are the origin of all blood cells

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- The pluripot. SC differentiate into 2 lines of
multipotential SC :

→ Lymphoid multipt. SC
Myeloid multipt. SC

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 * Blood cells’s Ontogeny

- Embryo consists of :
Amniotic-sac and yolk-sac, with an
embryonic-plate in between

Later the amniotic sac develop into Placenta ,

the Yolk-sac became the umbilical cord and
the embryonic plate grow as the embryo

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- yolk-sac’s primitive mesenchymal cells
develop the blood cells by aggregate the
primitive cells into clusters (blood-islands)
in the 3rd week :
- Blood island’s core → yolk-sac’s primitive
Stem-Cells → only produce embryonal RBC
(nucleated RBC, HbGower-1 δ 2ε2 )

- Blood island’s outer cells → vascular system

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  Blood cells development process

Bone
Yolk Sac marrow
Vertebra/Pelvis
Sternum
Liver Costa

Spleen Femur/long
bones

3 6 9 15 30 45
Gestational Age (year)
age Labor
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 The first fetal hemopoietic centre is Liver ( from
6-30 weeks fetal life) → since 24-weeks-old the
liver activities went down , and fetal marrow
start to become as hemopoietic centre .

Fetal’s liver hemopoietic activities practically

ended at birth .

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 Spleen together with liver acts as hemopoietic
centre , but after 24 weeks old, spleen only
produce lymphoid system together with thymus
and lymphoid glands .

 During adult life, if marrow tissue depressed ,

liver & spleen hemopoietic will be re-activated
(extramedullary hemopoiesis)

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 RBC’s morphological characteristics

- Hepatic phase :
no nucleus, macrocytic, Fetal-Hb (HbF, α2γ2)

- At birth (medullary hemopoiesis) :

mature RBC, normocytic, Adult-Hb (HbA, α2β2)
After 15 years-old hemopoietic activities in long
bones ceased and leave the activities only at
flat-bones (sternum, scapule, coxae and skull-
bones)

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 Hemopoiesis’s Stages

Stem Cells
↓ proliferation
Daughter’s cells
↓ diferentiation
Precursor-cells
↓ maturation
Erithrocyte - Leucocyte - Platelet

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 Proliferation :
 Proliferation ~ generation’s cycle
 Generation Time = time between 1 mitosis to
the next mitosis :
Mother’s cells (G1, active, diploid DNA ,
interphase) → DNA synthesis (S-phase) →
tetrapoid DNA (G2-phase, Prophase) →
Mitosis (M-phase, Metaphase-Anaphase-
Telophase) → 2 daughter’s cells (G1-phase)

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 In neonates- Childn Adult
infants/children : all
active parts of marrow
act as hemopoietic Marrow 1200- 2000-3500
centre → no ’s 1600 ml
hemopoietic tissue’s volume ml
reserve
Hemopo 1200- 1100 –
ietic 1600 1750 ml
tissue’s ml
volume.

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 In adult : marrow’s tissues replaced by fat tissue
(yellow-marrow) beginning from long bones →
hemopoietic activity only in flat-bones (pelvis,
sternum, vertebrae, skull)

 If ↑ blood cells production is needed → the

activities of the former hemopoietic centre ( long
bones, liver and spleen) are re-activated =
extramedularry hemopoiesis

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 Stem Cells Replication model :

 - Symmetrical Replication
- Asymmetrical Replication

* Asymmetrical Replication :
once the Stem Cells activate → 2 daughter-cells
→ 1 daughter-cell differentiate & maturate → 1
other daughter cell relocate the Stem cell’s
former position .

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 Symmetrical Replication :

- activated stem cell → differentiate & maturate

→ stimulates the other stem cell and
proliferate to become 2 daughter cells ; 1 of
them relocate the mother’s position and the
other daughter cell continue to differentiate
and maturate .
- Principally, the amount of Stem cells is rather
unchanged .

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 Erythropoiesis

 Erythropoiesis stimulated by Erythropoietin ,

hormone produced in the kidney .
This hormone is produced in response to low
tissue oxygen tension ; stimulates Stem Cells to
transform into proerythroblasts .

 Hb synthesis starts and ↑ with successive cell

divisions .

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 Leucopoiesis

 Leucopoiesis is under the control of Colony-

Stimulating Factors (CSFs) , i.e G-M
(Granulocyte-Macrophage) CSF

 Lymphoblasts give rise to Lymphocytes , some

lymph.precursors leave the marrow and mature
in the Thymus gland (produce T-lymphocytes)
and lymphocytes which mature in marrow are
called B-lymphocytes

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Myelocytic & Monocytic lines

 Granulocytic and Monocytic lines are derived

from same precursor – Myelomonoblast , but
with different maturation process :

- Granulocytic line ended as segmented

neutrophil in systemic circulation , and
monocytic line ended as macrophage in
tissues .

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 Hemopoietic Growth Factors :

 = glycoprotein hormon , regulates the

hemopoietic progenitors proliferation &
differentiation and the immature’s blood
cells function , locally activated or
circulate in plasma .

 GF sources :
- T-lymphocytes, Monocytes, Endothelial cells ,
Fibroblasts (Stroma cells) ; except
Erithropoitin that 90% produced in kidney
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  The action of GF regulated via specific
reseptor in target tissues/cells .
GF normally detected in plasma , or
only found in plasma in inflammation
or another stimulation .

 exmpl : Antigen and Endotoxin →

activate T-lymphocytes / Macrophages
→ release IL-1 and TNF → stimulate
another cells to produce GM-CSF, G-
CSF, M-CSF, IL-6 etc

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Thrombopoiesis

 To be mediated by Thrombopoietin hormone

 Platelet is fragments of the mature
megakaryocyte’s plasma
 Megakaryoblast does not divide during mitosis
and the cell simply increases its chromosome
numbers (endomitosis) which results in a giant
megakaryocyte with abundant cytoplasma from
which the platelets bud

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 Marrow’s Hemopoiesis Model

 Myeloid cells line :

- the most numerous cells with complete

maturation’s stages
- specific morphological changes.
- proliferation/mitosis capability still exists until
myelocytic stage .
- segmented neutrophils released to peripheral
circulation .
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 Marrow’s myeloid cells pooling :
- Mitotic-Pool (myeloid progenitor cells ,
myeloblasts, promyelocytes, myelocytes)

- Postmitotic-Pool (metamyelocytes, stabs &

segmented neutrophils)

Marrow’s pooling time : 6-10 days

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 Peripheral myeloid cells pooling :

 Marginal-Pool = neutrophils that located along

the vascular internal wall .

 Circulating-Pool = the circulating neutrophils .

the calculated neutrophil on CBC =

= circulating-pooled neutrophils.

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 It is possible for Neutrophils to move from
circulating pool to marginal pool (v versa) → the
Leucocyte count become ↑ or ↓

From Marginal-Pool to Circulating-Pool → 

leucocyte count :
- exercise / athletes
- certain medicamentous

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 Bone Marrow’s Aspiration
 Aspiration of marrow’s hemopoitics fluid to
evaluate hemopoitics appearance .

 It’s not uncommon that Aspiration followed by

marrow’s biopsy (done in Histo-Pathology
Department)

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 Marrow’s Aspiration Indication :

I. Diagnostic reasons :
1. Fever of unknown origin
2. Cytopenia
3. Monoclonal Gammopathy (Multiple
Myeloma )
4. Refractory Anemia

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 II. Approving Diagnosis :
1. Multiple Myeloma
2. Acute Leukemia
3. Megaloblastic Anemia
4. Hypersplenisme

III. Disease’s spreading / metastasis

IV. Treatment monitoring
V. Pre radiation/cytostatic preparation

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 Sites of Aspiration :

1. Spina Iliaca Anterior Superior (SIAS)

2. Spina Iliaca Posterior Superior (SIPS)

3. Sternum

4. Tibia (in children)

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 BMA Procedures :
1. ‘informed-consent’
2. Decide the aspiration location
3. Local-site desinfection (Betadin followed
with 70% alkohol)
4. Local Anaesthesia (Lidocain)
5. Local-site skin incision aseptically

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 6. Penetrate the aspiration’s needle through
incision wound (use Klima/Jamshidi’s
needles) by pressing and rotate the needle
clockwise until enter the marrow’s cavity

7. Aspirate the marrow’s hemopoietic fluid 0.2-

0.5 ml

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 8. Put the aspirate to a glass object , find the
right marrow’s fluid and make more than one
smear (2-3 smears with one imprint slide)

9. Make routine staining (Giemsa or Wright)

and Iron staining (Prussian Blue/Perl’s)
Left 1 routine smear and 1 imprint unstained
.

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 BMA’s Reports

1. Cellularity – compare the proportion of

hemopoietic tissue against the non-
hemopoietic (fat tissue , fibrous tissue etc)
2. M/E ratio (Myeloid/Nucleated Erythroid ) →
normal: 1.5:1 - 3.5:1
3. Cellular Activities :
- erythropoitic system
- myelopoitic system
- thrombopoitic system

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 4. Total Cellular Differential-counting :
- Neutrophilic series (53%) : Myeloblast
/ Promyelocyte / Myelocyte /
Metamyelocyte / Stab neutrophil /
Segmented neutrophil
- Eosinophil series (3.1%) : Myelocyte/
Metamyelocyte/Stab- Eosinophil /
Segmented-Eosinophil .
- Basophil/Mast Cells series (<0.1%)

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 - Erythrocyte series (25.6%) :
Pronormoblast/Baso-Normoblast /Poly-
Normoblast/ Ortho-Normoblast .
- Lymphocytic series (16.2%)
- Plasma cells series (1.3%)
- Monocytic series (0.3%)
- Megakaryocytic series (<0.1%)
- Reticular cells series (0.3%)

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 References

1. Hematology, Clinical Principles and

Applications, Rodak B.F., 3rd ed., W.B
Saunders Co, Philadelphia, 2007

2. Hematology in Clinical Practice, a Guide

to Diagnosis And Management, Hillman
R.S, Ault K.A, Rinder H.M., 4th ed.,
McGraw-Hill Medical Publishing Division ,
N.York, 2005

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 Selesai

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