HEMATOPOIESIS PHYSICAL EXERCISE
Ø Non athletes: TBV ↓ with 10% due to fluid
VOLEMIA (TOTAL BLOOD VOLUME)
DEFINITION: the sum of plasma volume and
blood cell volume
Ø Blood cell volume = 99% erythrocyte,
1% leukocytes and thrombocytes
NORMAL VALUES IN ADULTS:
• TOTAL BLOOD VOLUME (TBV)= ~5000
ml(7-8% of body weight)
Ø Male: 69 ml/kg
Ø Female: 65 ml/kg
• Plasma volume (PV) = ~3000 ml (55% of
TBV)
Ø Male: 39 ml/kg
Ø Female: 40 ml/kg
• Blood cell volume(BCV) = ~2000 ml (45% of
TBV)
Ø Male: 30 ml/kg
Ø Female: 25 ml/kg
Hematocrit (Ht)= (BCV x 100)/TBV; TBV=PV +
BCV = 3000 + 2000 = 5000 ml
Ht = (2000 x 100)/5000 = 40% (0,40 l/l)
Ht (%) normal level:
Ø Male: 45 ±7%
Ø Female: 42 ±5%
Ht% and TBV variation:
Ø normovolemia+ oligocythemia (Ht↓) = anemia
Ø normovolemia+ polycythemia (Ht↑) =
polyglobulia
Ø hypervolemia (TBV↑) + oligocythemia (Ht↓) =
hyperhydration
Ø hypovolemia (TBV ↓) + polycythemia (Ht↑) =
dehydration
VOLEMIA PHYSIOLOGICAL VARIATION
GENDER: TBV in male > TBV in female
Ø muscle mass ↑⇒ increased O2 consumption ↑⇒
erythropoiesis ↑⇒ ↑ BCV
AGE: TBV (ml/kg) new born > adult > elderly
Ø New born: perinatal hypoxia (↓PO2) ⇒
erythropoiesis ↑⇒ BCV ↑
Ø adult: ↑ fat issue % ⇒ PV ↓
Ø elderly: ↓ metabolic process ⇒VP ↓
PREGNANCY: TBV ↑with 20-30% in the last
trimmest of pregnancy
Ø ↑estrogen secretion⇒hydrosalin retention⇒ Pv↑
extravasation in the muscle intertitial space ( ↑
production of osmotic active catabolites )
Ø Athletes : TBV ↑ to 100 ml/kg due to efficient
mobilized blood from storage
EXTERNAL CONDITIONS
Ø altitude: TBV ↑ because of ↑ BCV (↓PO2
⇒altitude polycythemia)
Ø heet: TBV ↓ because of↓ PV (sweating)
POSTURE CHANGE
Ø Prolonged orthostatism: TBV ↓ with 15%
through ↑ interstitioal fluid volume
⇒edema
Ø Prolonged clinostatism: TBV ↓ by↓tissue
metabolism ⇒ PV↓
BLOOD FUNCTIONS
TRANSPORT FUNCTION
Ø transports O2 from lungs to tissues and CO2
from tissues to lungs
Ø transports nutrients to tissues
Ø transports metabolic wastes to organs to be
eliminated
Ø transports hormones and biological active
substances to cells
DEFENSE MECHANISM
Ø Non specific (phagocytosis) –leukocytes,
preformed substances
Ø Specific (imune)
Ø T lymphocytes, NK cells → cellular
mechanism
Ø B lymphocytes→immunoglobulin
→humoral mechanism
BODY UNITY- creates a direct connection
between
REGULATION
Maintains homeostasis = Water-electrolytic
balance, acid-base balance, osmotic balance
Temperature regulation
Regulates the main body functions
Ø Circulatory: regulates blood pressure
Ø Respiratory: regulates pulmonary exchanges and
ventilation
Ø Excretion: regulates the remove of metabolic
waste
Ø Digestive: regulates digestion, absorbtion and
motility
Ø Reproductive system
HEMATOPOIESIS defines
• Formation of mature blood cells, including all
the mechanism that ensure their continuous and
regular replacement.
• Begins in embryonic life and will be located in
the bone marrow at birth.
• In healthy adults, hematopoiesis is located in
hematogenous red marrow of trabecular bones.
Hematopoiesis
1. Progressive development of structural and
functional characteristics that are specific to a cell
series, after cell differentioation and maturation.
2. Continuous cell proliferation to maintain a
normal blood cells number.Proliferarea continua
celulara in vederea mentinerii in limite normale a
celulelor sanguine.
The uninterrupted production of peripheral blood
cells in ensured by a small number of hematopoietic
cells called Pluripotent stem cells
3. Cell origin and hematopoietic microenvironment
I – Pluripotent stem cells
II – Hematopoietic progenitors such as CFC-
GEMM, CFC-GM, E, M, Meg, Eo, Bazo, etc.
III – Hematopoietic cells that will form blood
series
ETAPELE HEMATOPOIEZEI
A. Embryonic and fetal hematopoiesis, has 3
phases, considering their anatomic site:
 Mesoblastic phase
 Hepatic phase
 Myeloid phase
B. Postnatal hematopoiesis is located only in the
bone marrow.
Hematopoiesis- Mesoblastic phase
Ø Begins in the 15 day of fetal life and will
th
continue for the next 6 weeks.
Ø located in the Yolk sac, where mesoblasts will
form mainly embryonic type erythroblast
(influenced by hematopoietic
microenvironment)- erythroblasts will contain
Hb Gower I and II.
Ø Embryonic type erythroblasts will differentiate
in 2 direnctions- peripheral cells will form blood
vassels and cental cells will form hematopoietic
progenitor cells.
Ø In this time, vascular channels that connect the
Yolk sac and embryo will develop-
hematopoietic stem cells will get to embryonic
circulation and then into the hematopoietic
organs..
Hematopoiesis - Hepatic phase
Ø Has a maximum activity in the 3rd-4th month and
it’s intensity will progressively decrease starting
the 6th month until birth.
Ø Located in the fetal liver, hematopoiesis will
occur extravascularly. Erythrocytes are
anucleated, macrocytic and contain Fetal Hb
(HbF). Production of granulocyte and
megakaryocyte also begins during hepatic
phase
Ø during the 4th month, primitive bone cavities
appear with the first stromal cells.
Ø during the 5th month hematopoiesis is maximum
in the fetal liver and spleen and will decrease
starting with the 6th month.
Ø In the 5th month, hematopoietic stem cells will
be found in the bone marrow cavity, starting
with the clavicle.
Hematopoiesis - myeloid phase
Ø begins in the fetal bone marrow and starts
with the 5th month. In the 7th month bone
marrow will be the most important site of
hematopoiesis, and after birth will be the
main site of hematopoiesis.
 Lymphatic tissue
Ø Is closely related to the formation of
hematogenous bone marrow.
Ø Appears in the lymphatic plexusin 9th week
and lymph glands in 11th week
Ø Spleen – during the period when
myelopoiesis declines, lymphopoiesis
occurs.
Ø Thymus – becomes lymphopoietic tissue in
the 9th , and will recive stem cells from liver,
spleen and bone marrow.
• After birth – lymphatic tissue is present in the bone
marrow, lymph nodes, thymus and Peyer’s patches.
Postnatal Hematopoiesis
• Physiologic located only in the bone marrow.
• At birth, hematopoiesis in located in all bone
cavities
• After the age of 5 years, it progressively
narrows, and in adult and adolescents will be
located only in flat bones: sternum, vertebrae,
epiphyses of long. At the age of 18, it weights
~2500 g.
• After the age of 20- the marrow of the long
bones is progressively loaded with lipids, and
will no longer produce erythrocites (except for
the proximal region of humeru and tibia)..
• Medullary production will decrease with age!
Hematopoiesis involves:
Ø Cell proliferation and self-renewal (cell
division)
Ø Differentiation and maturation: progressive
development of structural and functional
characteristics to each blood series .
Ø Hematopoiesis is maintained by pluripotent
hematopoietic stem cells.
Bone marrow structure - soft, spongy, gelatinous
tissue
Histology- 2 compatiments:
1. Vascular compartiment –medullary cavity of
the bone is partial divided by bone trabeculae;
2. Extravascular compartiment –
includeshematopoietic cells and medullary
microenvironment.
Located: in the cortical of long, short and flat
bones. It is crossed by bone trabeculae and is
formed of a venous sinuses network, surrounded by
extracellular matrix.
Bone marrow vasculature:
Ø nutrient artery - enters the marrow cavity of
long bones through the nutrient canal and
branches in 2 medullary arteries. These arteries
extend along the longitudinal axis and send off
radial branches that will reneter the endosteum,
reduce their caliber and drain into the Haversian
canals.
Ø After reentering the medularry cavity, the
arterioles open in a sinus network- some of them
oriented peripherally; most of them go towards
the center of the bone where they form a central
sinus from which blood drains through veins
and vessels into a common collecting trunk-
central longitudinal vein-which leaves the bone
through nutrient orifice.
Sinuses + radial arterioles + nutrient artery +
muscular artery= vascular compartiment
Characteristics of bone marrow vasculature:
Ø No lymphatic vessels (their role is taken over by
medullary sinusoids)
Ø Vascular sinus = the structural unit of bone
marrow vascularization, the barrier between
circulation and hematopoietic parenchyma,
where mature blood cells will pass from
hematopoietic parenchyma into vascular
compartiment.
Vasular sinuses are the counterparte of capillaries
of normal tissues and they present some
particularities:
a. Complete wall consisting in 3 layers:
Ø luminal (endothelium) –a single layer of
endothelial cells
Ø basal membrane
Ø external layer formed by a single row of
reticular cells (adventitia), that will form a
network in which hematopoietic cells are found
Basal membraine and the external layer
(adventitia) are discontonuous.
b. Some segments of the wall are formed only
of endothelium.
c. Other segments of the wall consists of
endotheliu, doubled by reticular extensions.
reticulare.
The space between sinuses containshematopoietic
cells and fat cells.
Endothelium consists of flat cells and is the only
constant and continuous component of the sinus
wall; perform an active endocytosis, presents
receprors for CSF, endothelial cells have
contractile capacity and produce changes in
sinusoidat surface.
Adventitial cells – are fixed reticular cells
Ø sinthetisizes reticulin fibers
Ø contains high concentration of FAL in their
membrane
Ø present CD10, CD13, HDL-DR I
Ø contain actin lamini, fibronectin, collagen
I,III,IV
Ø mesenchymal origin, related to fibroblasts with
CD34-
Ø rare mitoses, reduced phagocytic capacity
Ø they don not differentiate into hematopoietic
cells.
Adventitial cells + their extensions+ reticulin
fibres = medullary reticulum
Extravascular compartiment:
A. Hematopoietic cells
B. Medullary microenvironment
Hematopoietic cells
Ø Pluripotent and multipontent (HSC)
hematopoietic stem cells: characterized by a
high proliferative capacity (multiplication, self
renewal) and differentiation, influenced by the
microenvironment.
Ø Unipotent progenitor cells: have limited
proliferation capacity and high differentioation
capacity.
Ø Precursor cells: have limited proliferation
capacity and they differentiate into mature cells.
Ø Mature cells: are erythrocites, granulocytes,
monocytes, megakaryocites, lymphocites,
plasma cells.
Latent stem cells = stimulated by a cytokine
capabile to induce rapid proliferation; they will
form 2 types of cells : myeloid and lymphoid stem
cell
Ø Myeloid stem cell = multipotent cell that will
differentiate into various types of progentors
cells that will mature into: erythrocytes,
neutrophils, eozinophils, basophils, mast cells,
monocyte, platelets.
Ø Lymphoid stem cell generates B and T Ly
progenitors
Hematopoietic cells
Ø There is a specific distribution of
hematopoietic cells: cells are arranged “in
nests” in certain areas of the marrow.
Ø Erythocites are formed near sinuses (islands
of erythropoiesis
Ø Granulocytes are formed ar distance from
the sinus wall ( diffuse or in islands)
Ø Megakariocytes are located near adventitial
cells and the release of plateles will be
directly in the sinuses
HEMATOPOIETIC MICROENVIRONMENT
Ø Regulates proliferation and differentiation of
hematopoietic cells.
Ø Structure: stromal cells (endothelial cells,
fibroblasts, macrophage), smooth muscle cells
netede, adipocytes, chondrocytes, osteoblasts
and extracellular matrix (glycoprotein network
–supporting role).
Ø Synthesizes factors that regulate proliferarion
and differentiation of hematopoietic cells,
hematopoietic cells life span and mature
hematopoietic cells function
Hematopoitetic microenvironment signaling
pathway
1. Growth factors and Colony Stimulating
Factor (CSF)
Ø Stem cell factor (SCF): acts in the first stage of
hematopoiesis
Ø multiSCF or interleukin 3 (IL3): acts on all
progentors committed to a certain line
Ø Granulocyte-Monocyte Colony Stimulating
Factor (GM-CSF): stimulates proliferation and
differentiatioan of granulocytes and
monocyes/macrophages
Ø Granulocyte Growth Factor (G-CSF)
Ø Monocyte Growth Factor (M-CSF)
Ø interleukin 1 (IL1), IL2, IL4, IL5, IL6, IL7, IL8,
IL9, IL11, IL12, IL13.
Ø erythropoietin (Epo): stimulates erythropoiesis.
Ø thrombopoietin (Mpl-ligand): stimulates
megakariopoiesis and thrombopoiesis.
2. Hematopoiesis inhibitor factors:
Ø Tumor necrosis factor (TNF)
Ø Transforming grow factor (TGFβ): inhibitory
role in megakariopoiesis
Ø α, β and γ interpheron: inhibit G, MM, E, L
differentiation
Ø Prostaglandin E : inhibits monocyte
differentiation
Release of blood cells from bone marrow
Ø Blood cells leave medullary parenchyma and
enter venous sinuses by crossing the sinus wall,
though fenestration of endothelial cells.
Ø Cellular deformability regulates the passage
through the sinusoid wall (increases as the cells
mature):
Ø Immature cells are more rigid and remain in
extravascular space
Ø Mature cells (erythrocites, granulocytes,
monocytes) are more deformable and can pass
through sinusoid fenestrations.
Pluripotent HSC
Pluripotent HSC has a self renewal
capacity=maintaining a constant number of cells;
pluripotent HSC divides and produces:
1. HSC identical to mother cell- in order to
maintain a constant HSC number
2. HSC oriented towards a certain cell line,
with differentiation capacity.
Pluripotent HSC will differentiate and will result 2
Multipotent HSC.
Multipotent HSC
myeloid SC: CFU-GEMM(Granulo-erythro-
megakaryo-monocytic colony forming unit) will
form the follow series:
Ø erthrocyte: E-CFU (Erythroid colony forming
unit)
Ø myeloid: GM-CFU (Granulo-monocytic colony
forming unit)
Ø megakariocytic: MK-CFU (megakaryocytic
colony forming unit )
Limphoid SC: L-CFU (Lymphoid colony forming
unit ) that will form T and B lymphocyte
progenitors.
Multipotent HSC differentiates into progenitors
and has slef-renewal capacity.
Progenitor cells
Ø Cells commited to a certain lineage
Ø limited self renewal capacity;
Ø Cannot be identified using morphologicall
criateria;
Ø Through differentiation, they will form
precursor commited to a cell lineage.
Precursor cells
Ø sunt primele elemente celulare tinere;
Ø Cannot self differentiate ;
Ø mai sunt denumite celule cap de serie:
proeritroblasti, mieloblasti, monoblasti,
megacarioblasti;
Ø Can be identified using morphological criteria.
ERYTHROPOIESIS
Ø Erythropoiesis – mature red blood cells forming
process.
Ø Myeloid multipotent HSC will differentiate in
erythrocyte progenitors.
ERYTHROPOIESIS
Erythroid progenitors
Ø BFU-E (Burst Forming Unit- Erythroid)
Ø More primitive erythroid progenitor
Ø Large colony > 200 erythroblasts,
regulated by IL 3.
Ø CFU-E (Colony Forming Unit –Erythroid)
Ø More mature erythroid progenitor
Ø Small colony of 8-100 erythroblasts,
regulated by Erythropoietin
ERYTHROPOIESIS
Erythroid precursor
Morphological analysis will identify:
Ø Proerythroblast
Ø Basofilic Erythroblast
Ø Polychromatic Erythroblast
Ø Orthochromatic Erythroblast
Ø Reticulocyte
ERYTHROPOIESIS
Erythoid precursor maturation
Characteristics:
Ø cell and nuclear size will decrease;
Ø progressive increase of clumped chromatin;
Ø progressive decrease of nuclear-cytoplasmatic
ratio
Ø progressive increase of hemoglobin content (in
May-Grunwald- Giemsa stained smear has pink
appearence), meanwhile ribosomal RNA will
decrease (light blue tint), creating a
polychromatophilic appearence of the cell.
ERYTHROPOIESIS – Erythroid precursors
• Proerythroblast
• Large nucleated cell 14-19 μm
• Large nucleaus with nucleoli, reduced
basophilic cytoplasm (contains
ribosomes)
• Basofilic Erythroblast
• Small size cell 12-17μm
• Smaller nucleus,less visible nucleoli,
clumped chromatin
• Basophilic cytoplasm
• Polychromatic Erythroblast
• Relatively small cell 12-15μm
• Nucleus with no nucleoli
• Cytoplasm becomes more acidophilic
due to increased Hb
• Orthochromatic erythroblast
• Small cell 8-12μm
• Small nucleus, clumped chromatin
• Pink Cytoplasm due to Hb accumulation
• Reticulocyte
• Formed after nuclear expulsion of
orthochromatic erythroblast
• Larger size than Erythrocyte
• Contain: ribosomes, Golgi apparatus,
mitochondria and ARN- that will form a
basophilic network)
• synthesize Hb
• Released from bone marrow
• Pheripheral blood contains 0,5-1,5%
retyculocytes
ERYTHROPOIESIS
Ø Reticulocyte develops pseudopod and will get
between two endothelial cells;
Ø The pseudopod will gradually increase its
volume unltil the retyculocyte will enter blood
circulation.
Physiological erythropoiesis lasts 7 days
Ø from Proerythroblast to Reticulocyte: 3-5 days,
Ø Reticulocyte develop in 1-2 days in the bone
marrow,
Ø Subsequently, the reticulocytes pass into the
blood stream and circulate in this form for ~ 1-2
days,
Ø Apoi se transforma in eritrocite mature, care
sunt lipsite de ribozomi iar durata de viata a
eritrocitelor mature este de aproximativ 120 zile.
Reticulocytes will turn into mature erythrocytes
(Erythrocitytes have no of ribosomes; about 120
days life span)
Erythropoiesis regulation
ERYTHROPOIETIN stimulates the conversion rate
of CFU-E into proerythroblasts;reducing the period
of time necessary to go through the stages of
differentiation from proerythroblast to reticulocyte;
facilitates the rreticulocyte passage from bone
marrow to blood
EPO - α1 acid glycoprotein, 193 amino acids,
MW = 34kd - 80-90% is synthesized in glomeruli
and 10% is synthesized in extrarenal sites.
CELLULAR HYPOXIA stimulates Epo synthesis
and release :
decrease of partial oxygen pressure (pO2) -
hypoxemia: lung diseases, arterio-venous disease ,
altitude),
anemia (Hb decrease and erythrocytes decrease),
altered Hb molecule, with increased affinity for
oxygen and difficult O2 release.
Erythropoiesis regulation
Ø O2 transport capacity to tissues:
Ø anemia: ↓tissue PO2 ⇒↑EPO
Ø polyglobulia: ↑tissue PO2 ⇒↓EPO
Ø O2 tissue supply:
Ø altitude: ↓tissue PO2 ⇒↑EPO
Ø Respiratory failuare: ↓ tissue PO2
⇒↑EPO
Ø Increased O2 demands
Ø Physical exercise: ↓tissue PO2
⇒↑EPO,
Ø HORMONES
Ø Stimulating effect: testosterone,
cortisol, STH,
Ø Inhibitory effect: estrogens
ERYTHROPOIETIN:
Ø after its released in the blood stream, Epo binds
to Erythropoietin receptor (Epo R) located on
the membrane of erythroid cells in the marrow
Ø Epo and Epo R binding will trigger intracellular
signaling pathways that regulate gene activation
and will determine cell division and
differentiation.
Interleukin 3 (IL3) or multi CSF
Ø Released in hematopoietic
microenvironment by stromal cells
Ø Stimulates granulocyte, monociyte,
macrophage, erythrocyte and megakaryocyte
colony forming
Ø IL 3 has synergistic activity with Epo, GM-
CSF, G-CSF, IL6.
ERYTHROPOIESIS ADEQUATE SUPPLY: MONOCYTOPOIESIS
Proteins: amino acids; DEFINITION: proliferation, differentiation and
Minerals: iron, copper, cobalt, zinc; maturation of monocytic precursors in bone
Vitamins: vitamin B12, folic acid, B6, vitamin C, marrow
vitamin E; STAGES:
HEMOGLOBIN SYNTHESIS Ø CSP -> “myeloid “ stem cell
Ø Fe2+ + vitamin B6 -> HEM Ø “myeloid” stem cell -> Monoblast
Ø Amino acids -> GLOBIN Ø Monoblast -> Promonocyte
(a) PROGENITOR CELL MATURATION Ø Promonocyte -> monocyte
Ø vitamin B12 and folic acid Ø Monocyte -> macrophage (located in
(b) ANTIOXIDANT FACTORS tissues).
(Fe3+→Fe2+) MONOCYTE-MACROPHAGE SYSTEM =
Ø vitamin C and vitamin E monocytes + macrophages
(c) ENZYMATIC COFACTORS
Ø copper, cobalt, zinc
LYMPHOPOIESIS
LEUKOPOIESIS DEFINIŢIE: proliferation, differentiation and
DEFINITION: forming process of adult leukocytes maturation of lymphocytic precursors in the bone
from pluripotent stem cell marrow and thymus (central lymphoid organs).
Ø Granulopoiesis -> granulocyte STAGES:
Ø Monopoiesis -> monocyte a) In bone marrow:
Ø Lymphopoiesis -> lymphocyte Ø CSP -> “lymphoid” stem cell
LOCATED: in bone marrow and thymus Ø “lymphoid” stem cell ->
Ø reduced leukopoiesis during embrio-fetal Prolymphocyte:
phase; § B-lymphocyte ->mature B-
Ø Maternal antibodies cross placentar barrier lymphocyte,
and protect fetus during pregnancy § Mature natural killer (NK)
Ø active leukopoiesis at the end of pregnancy lymphocytes,
§ T lymphoblasts -> migrate into
GRANULOPOIESIS thymus
DEFINITION: proliferation, differentiation and b) In thymus :
maturation of granulocytic precursors in boner § T lymfphoblasts→ mature T
marrow Lymphocytes.
Ø CSP -> “myeloid” stem cell
Ø “myeloid” stem cell -> Myeloblast
Ø Myeloblast -> Promyelocite
Development of granulocytic line:
Promyelocytes -> myelocytes ->
metamyelocytes -> band neuthrophil ->
segmented neuthrophil -> (EO,NE,BA).
Maturation:
Ø decrease cell diameter;
Ø appearance of specific granulations;
Ø specific nucleus segmentation:
§ Bacterial infection – increased % of
immature NE with "kidney shape"
nucleus
§ Biermer anemia – increased % of
"hypersegmented” NE
MEGAKARYOPOIESIS Increases plateles number = thrombocytosis→ TPO
increases the fixation on the platelets → decrease of
DEFINITION: proliferation, endomytosis, free TPO →↓ megakariopoiesis
maturation şi cytoplasmic fragmentation of
trombocytic precursors in bonne marrow
STAGES:
Ø CSP -> Megakaryoblast
Ø Megakaryoblast -> Promegakaryocyte
Ø Promegakaryocyte -> Megakaryocyte
Ø Megakaryocyte -> Platelete.

MEGAKARYOPOIESIS

• ENDOMYTHOSIS
• Megakaryoblast characteristics→ polyploid
cell(8-64N)
• nuclear replication unfallowed by cell
division
• CYTOPLASMIC MATURATION
• Cell volume expansion
• Basophilia decrease
• Azurophilic granules
• cytoplasmic demarcation membranes
• CYTOPLASMIC FRAGMENTATION
• Cytoplasmic invasion by the membrane
cytosckeleton → compartments delimitation
or cytoplasmic fragments (platelets)
• 1 MEGAKARYOCYTE→2000-7000
PLATELETS

MEGAKARYOPOIESIS REGULATION
Depends on the number of circulating platelets
Decreased number of circulating platelets →
mobilization of splenic platelet deposit and
stimulates megakariopoiesis by TPO release
THROMBOPOIETIN(TPO) - stimulates
megakariopoiesis
Ø Growth factor structurally related to
EPO
Ø Produced in the liver, kydneys,
spleen, bone marrow
Ø Found in blood in two forms:
§ fixed (inactive) TPO→
circulating platelets receptors
§ free (active) TPO→ bone
marrow megakariocyte
progenitors receptors .
Decreased platelet number= thrombocytopenia →
TPO decreases the fixation on the platelets →
increase of free TPO → ↑ megakariopoiesis