Chap 10: Platelet Production, Structure and Function Flashcards
Nonnucleated blood cells that circulate at a concentration of 150 to 400 x10^9/L
Platelets
Platelets that arise from unique bone marrow cells are called
Megakaryocytes
Are the largest cells in the bone marrow and possess multiple chromosome copies (polyploid)
Megakaryocytes
Megakaryocytes account for less than what percentage of all bone marrow cells?
0.5%
Responding to the growth factor thrombopoietin (TPO), megakaryocyte progenitors are recruited from
Common myeloid progenitors
T/F: Megakaryocytes are also found in the lungs
TRUE
Megakaryocyte progenitors arise from the common myeloid progenitor under the influence of what transcription gene product?
GATA-1 regulated by cofactor FOG1
GATA-1 stands for
Globin transcription factor-1
FOG1 stands for
“Friend of GATA” (a product of the ZFPM1 (zinc finger protein multitype 1) gene)
Three megakaryocyte lineage-committed progenitor stages, defined by their in vitro culture colony characteristics arise from
Common Myeloid Progenitor
Least mature progenitor
Burst-forming unit (BFU-Meg)
Intermediate progenitor
Colony-forming unit (CFU-Meg)
More mature progenitor
Light-density CFU (LD-CFU-Meg)
These two are diploid and undergo normal mitosis to maintain a viable pool of megakaryocyte progenitor
BFU-Meg and CFU-Meg
All three progenitor stages resemble lymphocytes and CANNOT be distinguished by
Wright-stained light microscopy
Undergoes endomitosis
LD-CFU-Meg
A partially characterized form of mitosis unique to megakaryocytes in which DNA replication and cytoplasmic maturation are normal but cells lose their capacity to divide
Endomitosis
Forrm of mitosis that lacks telophase and cytokinesis (separation into daughter cells)
Endomitosis
Megakaryocyte progenitors leave the proliferative phase and enter
Terminal differentiation
Series of membrane-lined channels that invade from the plasma membrane and grow inward to subdi- vide the entire cytoplasm
Demarcation System (DMS)
Biologically identical to the megakaryocyte plasma membrane and ultimately delineates the individual platelets during thrombocytopoiesis.
Demarcation System (DMS)
Nuclear lobularity first becomes apparent as an indentation at the 4N replication stage, rendering the cell identifiable as an
MK-II stage, or promegakaryocyte
Ploidy levels are measured using _, a nucleic acid dye in megakaryocyte flow cytometry
Propidium iodide
The process of platelet shedding
Thrombocytopoiesis
A single megakaryocyte may shed
2000 t0 4000 platelets
Lifespan of platelets
8-9 days
First to appear on megakaryocyte progenitors and remains present throughout maturation
CD34 marker (along with CD36, CD42 and CD62)
A viral oncogene associated with murine myeloproliferative leukemia.
MPL
T/F: The plasma concentration of TPO is inversely proportional to platelet and megakaryocyte mass
TRUE
Elevate the platelet count in patients being treated for a variety of cancers, including acute leukemia.
Synthetic TPO Mimetics
A nonimmunogenic oligopeptide that is effective in raising the platelet count in patients with chronic immune thrombocytopenic purpura (ITP)
Commercial TPO mimetic, romiplostim (NPlate, Amgen)
Cytokines that function with TPO to stimulate mega- karyocytopoiesis include
IL-3, IL-6 and IL-11
Cytokines that function with TPO to stimulate mega- karyocytopoiesis include
IL-3, IL-6 and IL-11
Factors inhibit in vitro megakaryocyte growth, which indicates that they may have a role in the control of megakaryocytopoiesis in vivo
Ptelet factor 4 (PF4), B-thromboglobulin, neutrophil- activating peptide 2, IL-8,
Sometimes known as stress platelets, appear in compensation for thrombocytopeni
Reticulated platelets
Essential plasma surface-oriented glycosylated receptors that respond to cellular and humoral stimuli
Ligands or agonists
The plasma membrane surface that absorbs albumin, fibrinogen, and other plasma proteins, in many instances transporting them to internal storage organelles using a process called endocytosis
Glycocalyx
The plasma membrane invades the platelet interior, producing a unique _
Surface-connected canalicular system (SCCS
A condensed remnant of the rough reticulum
Dense tubular system (DTS)
DTS sequesters Ca2 and bears a number of enzymes that support platelet activation including
Phospholipase A2, cyclooxygenase, and thromboxane synthetase
Contractile in platelets (as in muscle) and anchors the plasma membrane glycoproteins and proteoglycans
Actin
Granules that are filled with proteins, some endocytosed, some synthesized within the mega- karyocyte and stored in platelets
Alpha granules
An integrin that binds the subendothelial collagen that becomes exposed in the damaged blood vessel wall, promoting adhesion of the platelet to vessel wall
A2B1
A key collagen receptor that also binds the adhesive protein thrombospondin
GP IV
Leucine-rich-repeat family CAM
GP Ib/IX/V
These platelet “agonists” are ligands for seven-transmembrane repeat receptors (STRs), so named for their unique membrane- anchoring structure
- Thrombin
- Thrombin receptor activation peptide (TRAP),
- Adenosine diphosphate (ADP),
- Epinephrine
- Serotonin,
- Thromboxane A2 (TXA2)
- Other prostaglandins)
Leads to an increase in intracellular calcium levels and contributes to initial platelet activation, shape change, and the formation of small reversible aggregates
P2Y1 signaling
Leads to a decrease in cyclic adenosine monophosphate (cAMP) levels and supports the formation of irreversible plate- let aggregates
P2Y12
A low-affinity receptor for the immunoglobulin Fc portion that plays a role in a dangerous condition called heparin-induced thrombocytopenia
FcyIIA (CD32)
An integrin that facilitates platelet binding to endothelial cells, leukocytes, and one another
P-selectin (CD62)
Platelet aggregation is a key part of primary hemostasis, which in arteries may end with the formation of a
White clot
White clot is composed primarily of
Platelets and vWf
Fibrin and red blood cells deposit around and within the platelet syncytium to form a bulky
Red clot
Red clot is essential to wound repair, but it may also be characteristic of inappropriate coagulation in venules and veins, resulting in
Deep vein thrombosis and pulmonary embolism
The polar phospholipid on which the factor IX/VIII (tenase) and factor X/V (prothrombinase) complexes assemble
Phosphatidylserine
Are membrane-derived vesicles that form in response to an activating stimulus that increases the platelet intracellular concentration of calcium
Microparticles
