Megakaryopoiesis, History Flashcards
Clonal assays of megakaryocytic progenitor cells begun
1970
Extraction of platelets
Apheresis
Process of formation of thrombocyte
Megakaryopoiesis
Maturation of megakaryocyte in the bone marrow
5 days
Doubling of DNA without cell division
Endomitosis
Discovered megakaryocyte
Howell
Progenitor of megakaryocyte
BFU-Meg
CFU-Meg
LD-CFU-Meg
Ways to differentiate progenitor
Immunologic probes or Flow cytometry
Cytochemical staining
Platelets are directly produced from the
Megakaryocyte cytoplasm
Identification of Megakaryoblast
GP Ib/IX/V
GP IV
mpl
Described platelets as extremely minute granules in blood
Addison
Cytochemical staining
Platelet peroxidase-ER
Platelet peroxidase-DTS
Cytochemical stain for progenitors, and megakaryoblast
Platelet peroxidase-ER
Blue cytoplasm with blunt projections
Megakaryoblast
Cytochemical stain for mature platelets
Platelet peroxidase-DTS
CD42b
GP-Ib
Megakaryoblast diameter
14-18um
Endomitosis is complete in what stage
Megakaryoblast
Fine chromatin
Megakaryoblast
15-40um in diameter
Promegakaryocyte
30-50um in diameter
Megakaryocyte
Criterion for the maturity of the cell
Chromatin pattern
Chromatin becomes coarse
Promegakaryocyte
NC ratio of 3:1
Megakaryoblast
NC ratio of Promegakaryocyte
1:2
Largest cell in circulation
Monocyte
Chromatin of megakaryocyte is already
Condensed
Cytoplasm is eosinophilic and granular
Megakaryocyte
Found in myeloproliferative or myelodysplastic disorder
Dwarf or micromegakaryocyte
CD 42
GP Ib/IX/V
CD36
GP IV
Largest cell in bone marrow
Megakaryocyte
Cytoplasm is pale blue and may contain pink granules reminiscent of mature platelets
Dwarf/micromegakaryocyte
How do platelets are released?
- Demarcation or invagination
- Fragmentation of cytoplasm
- Through micro tubular action proplatelets are formed
Pseudopodal extension of megakaryocyte
Proplatelets
Induce stem cell proliferation, induce proliferation and platelet released
Thrombopoietin
TPO is found in
Liver
Kidney
Smooth muscle
For early differentiation of stem cells
Il-3
Acts in the presence of TPO to enhance endomitosis, megakaryocyte maturation
IL 6 and 11
Neutralizer of heparin
PF4
Beta-Thromboglobulim
Inhibitors of Megakaryocyte growth
PF4 b-TG Neutrophil activating peptide-2 IL-8 FOG GATA-1 NF-E2
Newly released platelets
Reticulated platelets
Larger than mature platelets
Reticulated platelets
Platelet life span
8-11 days
Reticulate platelets
Stress platelets
6um in diameter
Stress platelets
Stress platelets in EDTA
Round
Stress platelets in citrate
Cylindrical and beaded
Stress platelets caryy
Free ribosomes and fragment of T
RER
Diagnosis of stress platelets and positive results
Flow cytometer
(+) result - 3k fold increase in fluorescence
Structure unique to platelets
Glycocalyx
Who also observed platelets adhesive qualities of increased stickiness when a vascular wall is damaged
Addison
Labeled antibody directed against GP Ib
Phycoerythrin
Nucleic acid dyes that bind RNA of ER
Thiazole orange
Anucleated blood cell with a diameter of 2.5um
Platelet
Normal value of platelets
150-400k
Platelets value at birth and women
Lower at birth
Higher in women
30% of platelets are seen in
Spleen
Triggers primary hemostasis
Platelet
Compose of tubulin
Microtubules
Circulating, resting platelets are what shape
Biconvex
Structure unique to platelets
Glycocalyx
Adhesive structure, that responds readily to hemostatic requirements
Glycocalyx
Platelet in EDTA
Round
Compose of tubulin
Microtubules
Cytoplasm of platelets are
Stain light blue with azurophilic granules
Surrounds the chromomere, non grab
Nular and clear to light blue
Hyalomere
Nucleus has slight lobulation
Promegakaryocyte
CD41
GP-Ib/IIIa
Immunologic probes
PF4 VWF HLA-DR GP-Ib GP-Ib/IIIa
Stabilizes membrane, maintains fluidity, and helps control transmembranous passage
Cholesterol
Flips and where coagulation enzymes assemble
Phosphatidylethanolamine
Intensely lobulated
Megakaryocyte
Platelet structure
Peripheral zone
Sol gel zone
Organelles zone
Membranous zone
Maintain negative charge surface of the platelets to avoid thrombus formation
Glycocalyx
Components of plasma membrane
Cholesterol
Fatty acids
Carbohydrates
Structure that provides phospholipids
Submembranous area
25nm in size, make up the mitotic spindle fibers
Microtubules
Migrates to plasma membrane and release their contents directly into plasma on activation
Dense core granules
Phospholipids located at the inner cytoplasmic layer
Phosphatidylinositol
Phosphatidylethanolamine
Phosphatidyl serine
Selectively permeable membrane
Plasma membrane
Structural support for normally discoid cell
Tubulin
Contract on activation to encourage expression of alpha granule contents
Microtubules
Anchors plasma membrane glycoproteins
Actin
Maintains the platelet structure
Microtubules
Provides rigidity to pseudopods
Microtubules
Structure for attachment
Pseudopods
Composition of microfilaments
Actin
Myosin
Causes platelets to contract
Actin
Dense granule that detected using lumiaggregometry “luciferase luminescence”
ATP
Contents of alpha granules flow to the?
Adjacent microenvironment
Adhesive structure, that responds readily to hemostatic requirements
Glycocalyx
Phospholipids located at the plasma layer
Phosphatidylcholine
Sphingomyelin
Thisdisorder stays gray in osmium dye in TEM
Gray plasma syndrome
Present throughout the cytoplasm
Actin
Regulates vascular permeability and regulates calcium mobilization in the bone
PF4
Fuse with SCCS
Alpha granules
Stabilizes membrane, maintains fluidity, and helps control transmembranous passage
Cholesterol
Flips and where coagulation enzymes assemble
Phosphatidylethanolamine
In resting platelet it is globular and amorphous
Actin
59-80% of the platelets composition
Alpha granules
Content of this granule participate in adhesion, aggregation and plasma coagulation
Alpha granules
Contents of alpha granules
Fibrinogen VWF Factor V and VIII PF4 P-selectin or CD62 B-thromboglobulin PDGF
Alpha granule for production of fibrin strand
Fibrinogen
Control center for platelets activation
DTS
Alpha granule that aids as an adhesion molecule
vWF
Labile factors. Easily consumed in circulation. Co factors for other coagulation
Factor V and VIII
Neutralizes or inhibits heparin
PF4
Alpha granule for endothelial cell and leukocytes binding
P-selectin or CD62
Aside from PF4, this granule also neutralizes heparin
B-thromboglobulin
Bulls eye
Dense core granules
Components of dense core granules
Calcium and magnesium
ADP
Serotonin
ATP
Dense granule for activation and coagulation
Calcium and magnesium
Calcium sequestering.
Positive staining for platelet peroxidase activity
DTS
Route for endocytosis and secretion of granular contents on activation
SCCS
Granule that is for repair and growth of damaged cells
PDGF
Diminished dense granules contents
Storage pool disorder
An inherited absence of alpha granules
Gray plasma syndrome
What happen to actin if the cytoplasmic calcium concentration increases
Actin become filamentous and contractile
Digest vessel wall components during in vivo aggregation
Lysosomes
Derived from rough ER
Dense tubular system
Indirect communication with the extra cellular environment
Surface connected canalicular system
Site for arachidonic acid metabolism within platelets
DTS
Digest autrophic debris
Lysosomes
Granule for vasoconstriction
Serotonin
Platelet structure
Peripheral zone
Sol gel zone
Organelles zone
Membranous zone
Maintain negative charge surface of the platelets to avoid thrombus formation
Glycocalyx
Gives bulk to the clot and gives tissue factor
PF4
Components of plasma membrane
Cholesterol
Fatty acids
Carbohydrates
Structure that provides phospholipids
Submembranous area
25nm in size, make up the mitotic spindle fibers
Microtubules
Migrates to plasma membrane and release their contents directly into plasma on activation
Dense core granules
Phospholipids located at the inner cytoplasmic layer
Phosphatidylinositol
Phosphatidylethanolamine
Phosphatidyl serine
Dense granule that support aggregation
ADP
Stains black with osmium
Dense core granules
Selectively permeable membrane
Plasma membrane
Structural support for normally discoid cell
Tubulin
Contract on activation to encourage expression of alpha granule contents
Microtubules
Anchors plasma membrane glycoproteins
Actin
Maintains the platelet structure
Microtubules
20-30nm in size, and it is platelets membrane surface
Glycocalyx
Phospholipids that supply arachidonic acid
Phosphatidylinositol
Provides rigidity to pseudopods
Microtubules
Structure for attachment
Pseudopods
Composition of microfilaments
Actin
Myosin
Causes platelets to contract
Actin
Dense granule that detected using lumiaggregometry “luciferase luminescence”
ATP
Contents of alpha granules flow to the?
Adjacent microenvironment
Phospholipids located at the plasma layer
Phosphatidylcholine
Sphingomyelin
Thisdisorder stays gray in osmium dye in TEM
Gray plasma syndrome
Present throughout the cytoplasm
Actin
Regulates vascular permeability and regulates calcium mobilization in the bone
PF4
Fuse with SCCS
Alpha granules
In resting platelet it is globular and amorphous
Actin
59-80% of the platelets composition
Alpha granules
Content of this granule participate in adhesion, aggregation and plasma coagulation
Alpha granules
Contents of alpha granules
Fibrinogen VWF Factor V and VIII PF4 P-selectin or CD62 B-thromboglobulin PDGF
Alpha granule for production of fibrin strand
Fibrinogen
Control center for platelets activation
DTS
Alpha granule that aids as an adhesion molecule
vWF
Labile factors. Easily consumed in circulation. Co factors for other coagulation
Factor V and VIII
Neutralizes or inhibits heparin
PF4
Alpha granule for endothelial cell and leukocytes binding
P-selectin or CD62
Aside from PF4, this granule also neutralizes heparin
B-thromboglobulin
Bulls eye
Dense core granules
Components of dense core granules
Calcium and magnesium
ADP
Serotonin
ATP
Dense granule for activation and coagulation
Calcium and magnesium
Calcium sequestering.
Positive staining for platelet peroxidase activity
DTS
Route for endocytosis and secretion of granular contents on activation
SCCS
Granule that is for repair and growth of damaged cells
PDGF
Diminished dense granules contents
Storage pool disorder
An inherited absence of alpha granules
Gray plasma syndrome
What happen to actin if the cytoplasmic calcium concentration increases
Actin become filamentous and contractile
Digest vessel wall components during in vivo aggregation
Lysosomes
Derived from rough ER
Dense tubular system
Indirect communication with the extra cellular environment
Surface connected canalicular system
Site for arachidonic acid metabolism within platelets
DTS
Digest autrophic debris
Lysosomes
Granule for vasoconstriction
Serotonin
Gives bulk to the clot and gives tissue factor
PF4
Dense granule that support aggregation
ADP
Stains black with osmium
Dense core granules
20-30nm in size, and it is platelets membrane surface
Glycocalyx
Phospholipids that supply arachidonic acid
Phosphatidylinositol
