MTAP W4 (Rodaks: Megakaryopoiesis/Platelets Flashcards
- nonnucleated blood cells
- diameter of 2.5 mm
- 150 to 400 x 10^9/L
- higher in women
- lower in both sexes when over 65 years old
Platelets
trigger primary hemostasis
Platelets
- Wright-stained wedge-preparation blood film
- 7 to 21 cells per 1003 field
platelets
- 30 to 50 mm in diameter- multilobulated nucleus and abundant granular cytoplasm
- 0.5% of all bone marrow cells
- are the largest cells in the bone
marrow and are polyploid, possessing multiple chromosome
copies - 2-4 per LPF
Megakaryocytes
product of the X chromosome gene
GATA
product of the ZFPM1 (zinc finger protein multitype 1)
gene
FOG1
In order of differentiation
least mature
burst-forming unit (BFU-Meg)
In order of differentiation
the intermediate
colonyforming unit (CFU-Meg)
In order of differentiation
the more mature progenitor
light-density CFU (LD-CFU-Meg)
All three progenitor stages of megakaryocytes resemble - and cannot be distinguished by Wright-stained light microscopy
lymphocytes
progenitor stage/s
participate in normal mitosis, maintaining a viable pool of megakaryocyte progenitors
BFU-Meg and CFU-Meg
progenitor stage
loses its capacity to divide but retains its DNA replication and cytoplasmic
maturation: ENDOMITOSIS
LD-CFU-Meg
is a form of mitosis that lacks telophase and cytokinesis (separation into daughter cells)
Endomitosis
Endomitosis
transcription slows
- GATA-1
- FOG1
Endomitosis
transcription factor; mediates the switch from mitosis to endomitosis by
suppressing the Rho/ROCK signaling pathway, which suppresses the assembly of the actin cytoskeleton
RUNX1
Endomitosis
transcription factor; DNA replication proceeds to the production of 8N, 16N, or even 32N ploidy with
duplicated chromosome sets
NF-E2
Some megakaryocyte nuclei
replicate five times, reaching -; this level of ploidy is unusual, however, and may signal hematologic disease
128N
A single megakaryocyte may shed - platelets
2000 to 4000
A single megakaryocyte may shed 2000 to 4000 platelets, a process called -
thrombopoiesis or thrombocytopoiesis
megakaryocytes: a total turnover rate of -days.
8 to 9 days
platelet production rises by as much as tenfold
thrombocytopenic purpura
As endomitosis proceeds, megakaryocyte progenitors leave the
proliferative phase and enter -
terminal differentiation
a series of stages in which microscopists become able to recognize their unique Wright-stained morphology in bone marrow aspirate
films
terminal differentiation
Morphologists call the least differentiated megakaryocyte
precursor the -
MK-I stage or megakaryoblast
Megakaryocyte Differentiation Stages
Nucleus: round
MK-I
Megakaryocyte Differentiation Stages
Nucleus: Indented
MK-II
Megakaryocyte Differentiation Stages
Nucleus: Multilobed
MK-III
Megakaryocyte Differentiation Stages
Chromatin: homogenous
MK-I
Megakaryocyte Differentiation Stages
Chromatin: moderately condensed
MK-II
Megakaryocyte Differentiation Stages
Chromatin: deeply and variably condensed
MK-III
Megakaryocyte Differentiation Stages
N/C ratio: 3:1
MK-I
Megakaryocyte Differentiation Stages
N/C ratio: 1:2
MK-II
Megakaryocyte Differentiation Stages
N/C ratio: 1:4
MK-III
Megakaryocyte Differentiation Stages
Cytoplasm: basophilic
MK-I
Megakaryocyte Differentiation Stages
Cytoplasm: basophilic and granular
MK-II
Megakaryocyte Differentiation Stages
Cytoplasm: azurophilic and granular
MK-III
Megakaryocyte Differentiation Stages
Endomitosis: present
MK-I
Megakaryocyte Differentiation Stages
Endomitosis: ends
MK-II
Megakaryocyte Differentiation Stages
Endomitosis: absent
MK-III
biologically identical to the megakaryocyte plasma membrane
and ultimately delineates the individual platelets during thrombocytopoiesi
DMS/demarcation system
Nuclear lobularity first becomes apparent as an indentation at the 4N replication stage, rendering the cell identifiable as an -
MK-II stage, promegakaryocyte
The promegakaryocyte reaches its full ploidy level by the end of the - stage
MK-II
the most abundant - stage, the
megakaryocyte is easily recognized at 103 magnification on
the basis of its 30- to 50-mm diameter
MK-III
ploidy levels are measured using
mepacrine
a nucleic acid dye in megakaryocyte flow cytometry
mepacrine
flow cytometric megakaryocyte membrane
marker
which is the TPO receptor site present
at all maturation stages
MPL
flow cytometric megakaryocyte membrane
marker
disappears as differentiation proceeds
CD34 marker
The platelet membrane
glycoprotein -
first appears on megakaryocyte progenitors and remains
present throughout maturation, along with immunologic
markers CD36, CD42, CD61, and CD62
glycoprotein IIb/IIIa
a marker located on the IIb portion
CD41
shows platelet shedding
Thrombocytopoiesis
- growth hormone
- 70,000 Dalton molecule
- possesses 23% homology with the red blood cell–producing
hormone erythropoietin
TPO
primary source of mRNA for TPO
liver
The plasma concentration of TPO is - proportional to platelet and megakaryocyte mass
inversely
also induces the proliferation and maturation
of megakaryocytes and induces thrombocytopoiesis, or platelet
release
TPO
a nonimmunogenic oligopeptide
that is also effective in raising the platelet count in immune
thrombocytopenic purpura
romiplostim
Other cytokines that function with TPO to stimulate megakaryocytopoiesis include interleukin -
3,6,11
interleukin: seems to act in synergy with TPO to induce the early differentiation of stem cells
IL-3
interleukin: act in the
presence of TPO to enhance the later phenomena of endomitosis, megakaryocyte maturation, and thrombocytopoiesis
IL-6 and IL-11
stimulates platelet production in patients with chemotherapy-induced thrombocytopenia
IL-11
transcription factors -
diminish megakaryocytopoiesis at the progenitor, endomitosis,
and terminal maturation phases
FOG1, GATA-1, and NF-E2
MARKERS:
MPL, TPO receptor by FCM
BFU-Meg
CFU-Meg
LD-CFU-Meg
MK-I
MK-II
MK-III
PLTs
MARKERS:
CD41: b3 portion of aIIbb3; peroxidase by TEM cytochemical stain
BFU-Meg
CFU-Meg
LD-CFU-Meg
MK-I
MK-II
MARKERS:
CD42; GP Ib portion of VWF
receptor, by FCM
PF4 by FCM
VWF by immunostaining
BFU-Meg
CFU-Meg
LD-CFU-Meg
MK-I
MARKERS:
CD34; stem cell marker by FCM
BFU-Meg
CFU-Meg
LD-CFU-Meg
MARKERS:
Fibrinogen
PLTs