HEMATOPOIESIS-Dr Putu Ristyaning Ayu, SP - PK

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HEMATOPOIESIS
dr. Putu Ristyaning Ayu, M.Kes, Sp.PK
Bag Patologi Klinik_FK UNILA
I. Pendahuluan
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A. Definisi
Hematopoiesis/ hemopoesis adalah proses pembentukan sel darah
produksi, diferensiasi, perkembangan serta pematangan dari semua
sel darah
B. Tempat/ Organ Hematopoiesis  berbeda sejak

pertumbuhan janin hingga dewasa
1. Normal  Sumsum Tulang/ bone marrow

2. Kelainan  Dalam beberapa keadaan (ex Leukemia)  extramedullar
sebagai organ primer hematopoiesis  organomegali
Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

Hematologi dan Transfusi Rukman Kiswari
I. Pendahuluan
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Some components (e.g., erythrocytes and platelets) complete

their development at medullary (i.e., bone marrow) sites,
whereas other components (e.g., T and B cells) complete
their development at extramedullary.
Foetus : 0 – 2 months  yolk sac

2 – 7 months  liver, spleen
5 – 9 months  bone marrow
Infants : Bone marrow (practically all bones)
Adults : vertebrae, ribs, sternum, skull, sacrum, proximal
ends of femur, proximal humerus

II. Sumsum Tulang/ Bone Marrow
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 Merupakan salah satu organ terbesar dalam tubuh  3-6%

BB dgn berat 1.500 gram pada dewasa
 Dalam sumsum tulang terdapat sel eritroid (eritrosit), sel
mieloid (leukosit), megakariosit (trombosit)  berbeda
dalam tahap pematangan
 Sumsum tulang tersusun atas sel stroma dan jaringan
mikrovaskuler  membentuk lingkungan yang cocok buat
sel punca

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Lifespan of blood cells:

 RBC 120 days
 platelet 10 days
 granulocytes circ : 9 hours
tissue : days
 lymphocyte circ : variable (hours to years)
tissue : weeks to years
Hematopoiesis
pluripotent
6 stem cell
trilineage myeloid stem cell

lymphoid stem cell
committed stem cells

Pluripotent
stem cell
Figure 1. Schematically summarizes the role of the major progenitor cells of
hematopoiesis
CFUGEMM Lymphoid
stem cell
BFUE CFUGMEo CFUbaso
Erythroid CFUEo
Progenitors CFUMeg CFUGM
CFUE
Thymus
CFU-M CFU-G
B T
Red Cells Platelets Mono- Neutro- Eosino- Baso- Lymphocytes

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta cytes phils phils phils
Winstrobe’s Clinical Hematology
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Normal Marrow
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myeloid to erythroid ratio = 3 : 1
dominant myeloid cells

myelocytes
metamyelocytes
granulocytes
dominant erythroid cells
polychromatophilic normoblasts
orthochromic normoblasts
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A. Stem cells  CFU (Colony - Forming Unit)

 Adalah sel-sel yg akan berkembang menjadi sel-sel
darah  eritrosit, leukosit, trombosit dan bbrp sel
dlm sumsum tulang spt fibroblast
 Sel induk yg paling primitif  pluripotent
(totipotent) stem cell
 Mempunyai sifat : self renewal, proliferatif,
diferensiatif

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 Menurut sifat diferensiasinya  sel induk hemopoetik dpt

dibagi:
a. Pluripotent (totipotent) stem cell
b. Committed stem cell
c. Oligopotent stem cell
d. Unipotent stem cell

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1. Pluripotential stem cells  3 main marrow cell lines :

a. Erythrocytes (red cells)
b. Granulocytes – monocytes (white cells)
c. Thrombocytes (platelets) and probably
lymphocytes (T & B lymp.,plasma cells)

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2. Multipotential stem cells  myeloid multi potential stem

cells and lymphoid multipotential stem cells.
- Myeloid multipotential stem cells :
* CFU-GEMM (CFU-S)  CFU granulocytes, erythrocytes,
monocytes and megakaryocytes; the earliest detectable
myeloid precursor
* CFU-C (CFU-GM)  CFU - granulocytes and monocytes

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* CFU-E and BFU-E

- CFU-E  CFU – erythropoiesis
- BFU-E  Burst - Forming Unit - erythroid 
committed to erythropoiesis and precursor of the
CFU-E
- CFU-E and BFU-E are dependent on Epo
* CFU-Meg
- progenitor of megakaryocytes
- derives from CFU-GEMM
- controlled by thrombopoietin
Tabel 1. Some hematopoietic progenitors cells
Term Required stimulus Postulated Role

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CFU-LM Multiple GF Pluripotent stem cell
CFU-GEMM GM-CSF, G-CSF, Pluripotent stem cell

(CFU-S) M-CSF, IL-3
CFU-GM GM-CSF, G-CSF, Committed progenitor of
(CFU-C) M-CSF, IL-3 granulopoiesis
BFU-E Erythropoietin, helper T Committed progenitor of
lymphocytes (IL-1, GM- erythropoiesis (early)
CSF, IL-3, IL-4)
CFU-E Erythropoietin Committed progenitor of
erythropoiesis (late)
CFU- Meg IL-3, GM-CSF, G-CSF. Committed progenitor of
thrombopoietin thrombopoiesis

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- Lymphoid multipotential stem cells  leave the bone

marrow and complete diff. in lymph nodes (B cells)
and thymus (T cells)

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B. Hematopoietic Growth Factors  CSF (Colony

stimulating factor)
Classification :
a. Non-lineage-specific GF  act on pluripotential and
multipotential stem cells to initiate self-renewal and
differentiation

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~ IL-3 (Multi-CSF)  induces the formation of

colonies granulocyte, monocytes, eosinophils,
erythroid cells, megakaryocytes and mast cells
production
~ GM-CSF  stimulates granulopoiesis and
macrophage production
b. Lineage-specific GF  act on the committed
progenitor cells and are involved in the diff. a
maturation of blood cells in the later stages of
hematopoiesis.

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These factors include :

~ Epo  stimulates erythropoiesis, mediates its feed-back
control
~ G-CSF  inducing formation of granulocyte and stimulates
proliferation of some leukemic cells
~ M-CSF  influencing macrophage prod.
~ Thrombopoietin  influencing CFU-mega

Table 2. Myeloid Hematopoietic Growth Factor
20 Factor Major Biological Activities in Vivo

Erythropoietin Stimulates erythropoiesis. Mediates its feedback
control
(Epo)
GM-CSF Stimulates granulopoiesis and macrophage
production
G-CSF Stimulates granulopoiesis and proliferation of
some leukemic cells
M-CSF Stimulates macrophage production
IL-3 (Multi-CSF) Stimulates granulocyte, monocyte, eosinophils,

erythroid cells, megakaryocyte and mast cells
production
Thrombopoietin Influencing CFU-mega
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C. Lymphokines and monokines

- released by lymphocytes and monocytes (macrophages)
 have wide-ranging  h.poietic effects through
extensive network of interaction involving immune
responses to infection and tumor invasion.

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- IL (Interleukin) : secreted by lymphocytes,

affect the function of other leukocytes (com-munication
links between leukocytes)
- engage in complex interactions with other IL, HGF and
many other protein such a TNF and lymphotoxins (Table 3)

Table 3. Lymphoid Hematopoietic Growth Factors
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Name Source Function
IL - 1 Macrophages, T Stimulates growth of T and B cells,
and B cells, mediates inflammation, inhibits growth of
fibroblasts some cancer cells.
IL - 2 (T T cells Binds to receptors on cytotoxic T cells,
promote their growth, stimulates growth of
cells GF)
helper T cells.
IL - 4 T cells, NK cells, Stimulates & regulates growth and diff. of T
mast cells and B cells, eosinophils and basophils.
IL – 5 T cells Regulates production of eosinophils.
Activates mature eosinophils.
(Eo–GF)
IL - 6 Lymphocytes, Promotes macrophage formation.
fibroblasts Stimulates IgG production by B cells.
IL-7 Stromal Cells Supports long-term survival of B and T
cells in vitro.
IL - 8 Fibroblasts, Enhancement of neutrophil function
vasc. endot. Hematologi dan Transfusi Rukman Kiswari
III. Limpa/Spleen
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 Organ berukuran relatif kecil  beratnya sekitar 8 0ns,

menerima 5% dari curah jantung/mnt
 Limpa organ yg dipenuhi sel darah
 Fungsi limpa: reservoir, filtrasi

ERITROPOIESIS
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 Eritrosit mengandung hemoglobin  transportasi O2 dan

CO2
 Umur eritrosit 120 hari
 Eritropoiesis  proses produksi eritrosit
 Proses  diferensiasi dari sel induk menjadi eritrosit matang
 Zat penting untuk produksi Hb  asam amino (protein),
Fe, Vit B12, Vit B6, asam folat, mineral kobalt (Co), Nikel
(Ni)
 Pada orang dewasa  eritrosit membutuhkan > 20 mg
elemen Fe
 Eritropoiesis abnormal  akibat def salah satu zat yg
diperlukan  anemia
MATURATION STAGES RBC
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STEM CELLS
PRONORMOBLAST
BASOPHILIC NORMOBLAST
POLYCHROMATOPHILIC NORMOBLAST
ORTHOCHROMATOPHILIC NORMOBLAST
RETICULOCYTE
MATURE RED CELL

ERITROPOIESIS
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Pool of nucleated erythroid precursor in marrow

~ 2%  pronormoblast
~ 18%  basophilic normoblast
~ 54%  polychromatophilic normoblasts
~ 26%  orthochromatophilic normoblasts
Sel darah merah berinti (normoblasts) muncul dalam darah
jika proses eritropoiesis terjadi di luar sumsum tulang (e.
Medullary) dan juga pada penyakit di sumsum tulang.

ERITROPOIETIN
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 Merupakan suatu substansi yang diproduksi terutama oleh

ginjal hormon glikoprotein, dgn BM 46.000 yg berfs
merangsang eritropoiesis dan dpt melewati sawar plasenta
antara ibu dan janin
 Tempat sintesisnya  sel peritubular dlm ginjal, << hati
 Normal  kadar eritropoietin dlm plasma 20 mU/mL
20.000 bila terjadi hipoksia  anemia
 Eritropoietin juga berinteraksi IL3, GM-CSF, IL1,
thrombocytopiesis stimulating factor (megakariosit)

GRANULOPOIESIS
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 Leucocyte or white cell  refer to any of the nucleated cells

normally present in blood, whose major function is defense
against foreign invaders
 Types of leucocytes :
- Type of defense function : phagocytes (i.e., granu-
locytes and monocytes) and immunocytes (i.e.,
lymphocytes and plasma cells)

GRANULOPOIESIS
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- Shaped of the nucleus  polymorphonuclear or mononuclear

- Site of origin  myeloid or lymphoid
- Presence of absence of specific- staining granules 
granulocytes or non-granulocytes

Maturation stages granulosyte
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MYELOBLAST
PROMYELOCYTE
MYELOCYTE
METAMYELOCYTE
BAND FORM
MATURE PMN GRANULOCYTE

1. NEUTROPHILS
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 Functions : ~ Chemotaxis
~ Cytotoxic activities : phagocytosis
and granule toxicity
 Life span and circulation :
~ Transit time in blood for mature neutrophils :
1 day or less.
~ Probably survive 1-2 days in tissue.
~ N peripheral blood levels : 4.0 – 10 x 103/ul

2. EOSINOPHILS
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 Functions :
~ a first line defense against parasites
~ modulate hypersensitivity reactions
~ migrate to inflammatory sites
~ Usually exist in concentr. of 100-400/ul in PB
~ BM maturation time : 2-6 days , circ. half life : 6 - 12 hours

3. Basophils and Mast cells
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 Functions : ~
involved in immediately hypersensitivity
~ trigger anaphylactic degranulation
~ active arachidonic acid metabolites
(e.g..leukotrienes, prostaglandin)
~ Basophils : about 1-2 days
~ Mast cells : present in blood only in pathologic
conditions. Mast cells survive several weeks to
several month in tissue

4. MONOCYTES
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 Functions : Morphology :
~ Activating stimuli Monoblast
~ Chemotaxis
~ Phagocytosis Promonocytes
Monocytes
 Life span :
4.5 – 10 hours (mean 8.5 h)

LYMPHOCYTOPOIESIS
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 There are three major functional classes of lymphocytes : B

lymphocytes (B cell), T lymphocytes (T cell) and Natural
Killer (NK cell)
 Differentiation :
~ B - lymphocyte diff. in BM :
Early pre-B cell
pre B-cell
immature B cell
mature B cell
LYMPHOCYTOPOIESIS
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~ T-lymphocyte diff. in the thymus :
Pre-T cell (thymic lymphoblast)
Early thymocyte (large cortical thymocyte)
Intermediate thymocyte (small c. thymocyte)
Late thymocyte (medullary thymocyte)
Mature T cell

LYMPHOCYTOPOIESIS
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Function
~ B cell function : humoral immunity (i.e.,anti

body/immunoglobulins production)
~ T cell function : cell-mediated immunity including delayed

hypersensitivity, graft rejection, contact allergic reaction
 Life span : years

THROMBOPOIESIS
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 Blood platelets play an essential role in hemostasis,

thrombosis and coagulation of blood
 The platelet count ranging from 150,000-450,000/ul
 Life span : 8 to 12 days
 Functions : Platelets participate in the formations of a
platelet plug and a stable fibrin clot (adhesion and
aggregation)

Maturation stages thrombopoeisis
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Pluripotential stem cell  CFU-Meg  Megakaryoblast


Proliferation
CSF-Mega
 Megakaryocyte maturation  Platelet shading
Thrombopoietin (TP)

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1

B. Tempat/ Organ Hematopoiesis  berbeda sejak

1. Normal  Sumsum Tulang/ bone marrow

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

Some components (e.g., erythrocytes and platelets) complete

Foetus : 0 – 2 months  yolk sac

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

 Merupakan salah satu organ terbesar dalam tubuh  3-6%

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

Lifespan of blood cells:

trilineage myeloid stem cell

committed stem cells

BFUE CFUGMEo CFUbaso

Red Cells Platelets Mono- Neutro- Eosino- Baso- Lymphocytes

myeloid to erythroid ratio = 3 : 1

dominant myeloid cells

A. Stem cells  CFU (Colony - Forming Unit)

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

 Menurut sifat diferensiasinya  sel induk hemopoetik dpt

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

1. Pluripotential stem cells  3 main marrow cell lines :

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

2. Multipotential stem cells  myeloid multi potential stem

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

* CFU-E and BFU-E

Term Required stimulus Postulated Role

CFU-LM Multiple GF Pluripotent stem cell

CFU-GEMM GM-CSF, G-CSF, Pluripotent stem cell

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

- Lymphoid multipotential stem cells  leave the bone

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

B. Hematopoietic Growth Factors  CSF (Colony

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

~ IL-3 (Multi-CSF)  induces the formation of

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

These factors include :

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

20 Factor Major Biological Activities in Vivo

IL-3 (Multi-CSF) Stimulates granulocyte, monocyte, eosinophils,

C. Lymphokines and monokines

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

- IL (Interleukin) : secreted by lymphocytes,

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

 Organ berukuran relatif kecil  beratnya sekitar 8 0ns,

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

 Eritrosit mengandung hemoglobin  transportasi O2 dan

MATURE RED CELL

Pool of nucleated erythroid precursor in marrow

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

 Merupakan suatu substansi yang diproduksi terutama oleh

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

 Leucocyte or white cell  refer to any of the nucleated cells

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

- Shaped of the nucleus  polymorphonuclear or mononuclear

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

MATURE PMN GRANULOCYTE

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

Hematologi Klinik Ringkas Prof.Dr. I Made Bakta

 There are three major functional classes of lymphocytes : B

~ T-lymphocyte diff. in the thymus :