Platelet Prt. 1

Question 1

Megakaryocytopoiesis

Arise from

Answer 1

common myeloid progenitor

Question 2

Megakaryocytopoiesis

Promoted by:

Answer 2

Globin Transcription Factor-1 (GATA-1),

Friend of GATA (FOG-1)

Question 3

Megakaryocytopoiesis

Suppressed by:

Answer 3

MYB (myeloblastosis transcription factor)

Question 4

MEGAKARYOCYTE PROGENITORS
Three progenitor stages:

Answer 4

1. Burst-forming unit megakaryocyte (BFU-Meg)
2. Colony-forming unit megakaryocyte (CFU-Meg)
3. Light-density colony-forming unit megakaryocyte (LD-CFU-Meg)

Question 5

Progenitor that undergoes Endomitosis

Answer 5

Light-density colony-forming unit megakaryocyte (LD-CFU-Meg)

Question 6

mediates the switch from mitosis to endomitosis

Answer 6

RUNX1

Question 7

suppresses the Rho/ROCK signaling pathway

Answer 7

RUNX1

Question 8

mediates the switch from mitosis to endomitosis

Answer 8

RUNX1

Question 9

RUNX1 suppresses the…

Answer 9

Rho/ROCK signaling pathway

Question 10

Development of a-granules, dense granules,

demarcation membrane system

Answer 10

MK-I (MEGAKARYOBLAST)

Question 11

: membrane-lined channels that subdivide the cytoplasm in megakaryoblast

Answer 11

DMS

Question 12

Nuclear indentation

Answer 12

MK II (PROMEGAKARYOCYTE)

Question 13

Easily recognized
30-50 um in diameter
Intensely indented/lobulated nucleus
Higher ploidy = higher lobulation
Azurophilic cytoplasm

Answer 13

MK III (MEGAKARYOCYTE)

Question 14

THROMBOCYTOPOIESIS (PLATELET SHEDDING)

A single megakaryocyte sheds…
Lifespan:___

Naked megakaryocyte nuclei consumed by..

Answer 14

2,000-4,000 platelets

8-9 days

marrow macrophages

Question 15

Easily recognized
30-50 um in diameter
Intensely indented/lobulated nucleus
Higher ploidy = higher lobulation
Azurophilic cytoplasm

Answer 15

MK III (MEGAKARYOCYTE)

Question 16

MEGAKARYOCYTE MEMBRANE RECEPTORS AND MARKERS

Stem cell, common myeloid progenitor marker

Answer 16

CD34

Question 17

MEGAKARYOCYTE MEMBRANE RECEPTORS AND MARKERS

TPO receptor
Seen in all maturation stages

Answer 17

MPL receptor

Question 18

MEGAKARYOCYTE MEMBRANE RECEPTORS AND MARKERS

Seen throughout maturation

CD36 (GPIV), CD42 (GPIb), CD62 (P-selectin)

Answer 18

GP IIB/IIIA

(CD41/CD61)

Question 19

MEGAKARYOCYTE MEMBRANE RECEPTORS AND MARKERS

Fully mature Megakaryocyte

Answer 19

FACTOR VIII, VWF, Fibrinogen

Question 20

= Low platelet, Mk mass

Answer 20

High TPO

Question 21

Hormones and Cytokines That Control Megakaryocytopoiesis

Answer 21

Thrombopoietin
IL-3
IL-6
IL-11

Question 22

In compensation for thrombocytopenia

Stained with_____

Answer 22

RETICULATED/STRESS PLATELETS

thiazole orange

Question 23

_______
o Supplies arachidonic acid for the synthesis of TXA2

Answer 23

Phosphatidylinositol

Question 24

Lipid bilayer
o Outer layer

Answer 24

1. Phosphatidylcholine
2. Sphingomyelin

Question 25

Lipid bilayer Inner layer

Answer 25

1. Phosphatidylinositol 2. Phosphatidylethanolamine 3. Phosphatidylserine

Question 26

o Platelet membrane surface o 20-30 nm thick o Adhesive o May facilitate endocytosis o Negatively charged

Answer 26

Glycocalyx

Question 27

 Allows the platelet to store additional hemostatic proteins.  Allows enhanced interaction of the platelet with the environment.  Route for endocytosis and secretion of a-granules

Answer 27

SURFACE-CONNECTED CANALICULAR SYSTEM (SCCS)

Question 28

 Condensed remnant of the RER  Sequesters calcium, contains PLA2, COX, thromboxane synthas

Answer 28

DENSE TUBULAR SYSTEM (DTS)

Question 29

Maintains discoid shape  Move inward on platelet activation to release a-granules  Reassembles during platelet shape change to form pseudopodia

Answer 29

MICROFILAMENTS AND MICROTUBULES

Question 30

 Parallel to the outer surface of platelet  8-20 tubules, with multiple subunits of tubulin  Disassembles at refrigeration or with colchicine = round shape

Answer 30

CIRCUMFERENTIAL MICROTUBULES

Question 31

 Parallel to the outer surface of platelet  8-20 tubules, with multiple subunits of tubulin  Disassembles at refrigeration or with colchicine = round shape

Answer 31

CIRCUMFERENTIAL MICROTUBULES

Question 31

Anchors plasma membrane glycoproteins and proteoglycans

Answer 31

MICROFILAMENTS WITH ACTIN

Question 32

 Desmin, vimentin  Connects with actin and tubules to maintain platelet shape

Answer 32

INTERMEDIATE FILAMENTS

Question 33

a-GRANULES/LIGHT GRANULES _____ granules per platelet  Stains____  Proteins within a-Granules are either endocytosed or synthesized within the megakaryocyte  Several are membrane-bound  Released via____

Answer 33

50-80 medium gray SCCS

Question 34

DENSE GRANULES  _____per platelet  Appear later than alpha granules during Mk differentiation  Stain_____  Released directly into the plasma

Answer 34

2-7 black (opaque)

Question 35

Platelet dense granules content

Answer 35

ADP ATP Serotonin Ca2 + Mg2

Question 36

Ligand: collagen, vitronectin, laminin, fibronectin

Answer 36

GPla/lla

Question 37

Ligand: collagen

Answer 37

GPVI

Question 38

VWF and thrombin bind GPIba thrombin cleaves a site on GPV

Answer 38

GPIb/IX/V

Question 39

Ligand: Fibrinogen, VWF

Answer 39

GPIlb/Illa

Question 40

PLATELET ADHESION Injury to the BV wall exposes_____ to the blood Damaged ECs release____ vWF binds to site of injury by binding to collagen VWF binds to____, tethering platelets to site of injury _____binds to Type I fibrillar collagen, triggering an outside-in reaction releasing TXA2, ADP a. *_____ binds to TPa, TPB b. *____ binds to P2Y1, P2Y12 Binding of TXA2, ADP to receptors increases affinity of Integrin a2ß1 to collagen

Answer 40

collagen vWF GPlba GPVI TXA2, ADP

Question 41

PLATELET AGGREGATION 1. Vessel injury exposes_____ 2. TF triggers the production of____, cleaving PAR1, PAR4 3. Generation of the___ and ____ 4. Activation of _____= platelet aggregation

Answer 41

Tissue factor thrombin collagen and thrombin activated platelet GPIlb/Illa receptor

Question 42

Plt aggregation Platelets change shape (discoid to round with pseudopods) Increase the surface area, enhance platelet binding Endpoint: White clot Red clot

Answer 42

White clot (arteries), Red clot (veins)

Question 43

PLATELET SECRETION Contraction of____ & ____ Contents of a-Granules, lysosomes flow through____ Contents of Dense Granules migrate to plasma membrane and are directly secreted

Answer 43

actin microfilaments, intermediate filaments SCCS - Surface Connected Canalicular System

Question 44

PLATELET SIGNALING PATHWAYS aßy heterotrimers which bind GDP when inactive Membrane receptor-ligand binding ***promotes GDP release and replacement with GTP***

Answer 44

G-Proteins

Question 45

Eicosanoid pathway

Answer 45

GO receptor + Ligands -> Phospholipase A2 -> Phosphatidylinositol -> Arachidonic Acid -> PGH2 -> TXA2

Question 46

TXA2 binds to___

Answer 46

Thromboxane receptor then inhibits adenylate cyclase Decreasing CAMP Increasing intracellular calcium Releases granules and forms pseudopods

Question 47

Pathway that inactivates platelets

Answer 47

Cyclooxygenase pathway

Question 48

Endpoint of cyclooxygenase pathway

Answer 48

PGI2/ prostacyclin

Question 49

Prostacylins inhibits…

Answer 49

CAMP Decreasing intracellular calcium Supresses platelet activation

Question 50

IP3-DAG pathway G-protein dependent

Answer 50

INOSITOL TRIPHOSPHATE-DIACYLGLYCEROL ACTIVATION PATHWAY

Question 50

Half-life: 30 seconds Diffuses from the platelet Spontaneously reduced to Thromboxane B2 Importance: platelet activation

Answer 50

TXA2