Platelets Flashcards
What are platelets?
Cellular fragments of megakaryocytes
True or false: platelets are anuclear.
True
Platelets are approximately _____ to four µm in diameter, but can be larger.
One
What is the platelet reference range?
150-400 x10^9/L
What is the in-vivo lifespan of platelets?
~10 days
Mean platelet volume (MPV) is useful, but less reliable than an MCV value, and is generally ≤___ fL
10
List the order
which proliferation and maturation of precursor megakaryocytes in bone marrow follows.
Common myeloid progenitor
Megakaryoblast progenitor
Megakaryoblast
List two cells of the megakaryocytic lineage.
Actively-proliferating progenitor cells
Post-mitotic (non-proliferating) megakaryocytes
What term is given to the process of platelet differentiation?
Endomitosis
______________ and release time is generally approximately four to seven days.
Proliferation
List six features of a megakaryoblast.
14-18 µm in diameter
Scanty, basophilic cytoplasm
May have azurophilic granules
Pseudopodia
Lace-like, fine, purple-red chromatin
Smudged, condensed granular nuclear chromatin areas
Describe a promegakaryocyte.
15-40 µm in diameter
Abundant cytoplasm, with basophilia that fades during maturation
Cytoplasmic granules
Smudged nucleus, which may be round, indented, or lobulated
Coarse, thick-strand chromatin, of a purple-reddish colour
State five features of the mature megakaryocyte.
30-50 µm in diameter
Platelets form on the outer edge of the cytoplasm
Vacuoles
Lobed nucleus
Abundant, light blue cytoplasm, with fine azurophilic granules
Platelets are released directly into the sinuses of the bone marrow, in groups called _______________.
Proplatelets
The __________ of megakaryocytes stay in the marrow and degenerate.
Nuclei
Two-thirds of released platelets enter circulation; the remainder are sequestered in the ___________.
Spleen
Platelet mass in circulating blood, and _____________ ________ in the marrow, stimulate production.
Megakaryocyte mass
__________, together with growth factors, promote progenitor cells.
Cytokines
What cytokines are used for platelet proliferation?
IL-3 and GM-CSF
List two cytokines involved in platelet maturation.
IL-6 and IL-11
_______________ (TPO) influences all stages of megakaryocyte production, independently or in synergy with cytokines.
Thrombopoietin
What organ constitutively produces thrombopoietin?
Liver
True or false: thrombopoietin and erythropoietin are not structurally related.
False
What is thrombopoietin’s receptor called, and where is it found?
CD110 (c-Mpl); found on circulating platelets and progenitors
Binding of TPO with platelet promotes _____________ of the platelet.
Activation
Low platelet count means more __________TPO, and this can stimulate progenitor cells to proliferate.
Free
TPO levels are regulated by platelet __________.
Mass
Upon binding to Mpl receptors on platelets, TPO is ________________________________________________________________________________.
Internalized and removed from circulation.
In the case of __________________, much TPO is removed from circulation, resulting in low levels of TPO signalling.
Thrombocytosis
During thrombocytopenia, little TPO is cleared from circulation, resulting in _________ ____________ of TPO signalling.
High levels
MK interact with ___________ ____________ cells.
Marrow stromal
Stromal cells produce positive and negative ______________ of MK growth.
Regulators
Stromal cells have ligands for __________ proteins, which influence lineage choice of MEP for RBCs or platelets.
Notch
What factor augments TPO?
Stromal cell-derived factor-1 (SDF-1)
MK is found primarily in vascular niche, physically attached to endothelial cells lining ___________ vessels.
Sinusoidal
Platelets are _______-shaped, with a flat surface.
Disc
Platelets repel each other and repel ___________ cells.
Endothelial
List three features or functions of the glycocalyx.
Made up of glycolipids, integral membrane glycoproteins, and proteoglycans, and adsorbed plasma proteins (albumin, fibrinogen, etc.)
Reflects interaction of platelet with extracellular medium
Responsible for negative charge of platelet surface
The ____________ ___________ is the former demarcation membrane of parent megakaryocyte.
Platelet membrane
List four functions of platelets.
Adhesion
Secretion
Aggregation
Contraction
Name and describe one system which the platelet membrane invaginates to form.
Open canicular system, that involves numerous invaginations of the platelet surface, and is a direct connection between the interior and surface of the platelet
List two neutrally-charged platelet membrane phospholipids.
Phosphatidylcholine (PC)
Sphingomyelin
PS and PE are ____________-charged platelet membrane phospholipids.
Negatively
True or false: arachidonic acid is not found in platelet membranes.
False
Outline the events and features of the inactive resting membrane state of platelets.
Neutral phospholipids are located on the external leaflet of the membrane. PS and PE are localized to the inner surface of the membrane. Asymmetry is maintained by ATP-dependent enzymes (flippase and floppase). When cells are activated or injured, they shuffle the PS and PE to the outer membrane leaflet. The process is controlled by a variety of enzymes, including scramblase.
The inactive membrane resting state is essential to ____________ haemostasis.
Secondary
GP-Ib/IX/V bind to VWF, __________, and ristocetin.
Thrombin
GP-Ib/IX/V involve primary ______________ receptors.
Adhesion
GP-IIb/IIIa (CD41/61) bind to _______________ and VWF.
Fibrinogen
GP-IIb/IIIa (CD41/61) involves primary ______________ factors.
Aggregation
GP-Ia/IIa (CD49b/CD29) bind to _____________.
Collagen
GP VI (in complex with ________) binds to collagen.
FcRy
List two substances to which GP-IV (CD36) binds.
Collagen and thrombospondin
List three functions of the platelet’s structural zone.
Structural support for the platelet
Maintains discoid shape in the resting state
Allows the cell to change shape when activated
______________ (composed of tubulin), and a network of proteins (actin, actin-binding protein, and several other proteins) make up the cytoskeleton.
Microtubules
List three components of the organelle zone of platelets.
Mitochondria
Granules
Glycogen particles
True or false: the organelle layer lies above the microtubules.
False
Identify the four types of platelet granules.
Dense bodies
Alpha
Lysosomal
Microperoxisomes
___________ are storage sites for proteins, and other substances necessary for platelet function.
Granules
List four major features of alpha granules.
Form the greatest granule subpopulation (50-80 per platelet)
Variable in size and content
Contain substances that are intrinsic to the platelet
Also contain many proteins that are absorbed from the plasma, and not synthesised by the megakaryocyte
_____________ __________ contain mediators of platelet function and haemostasis, such as nucleotides (ADP, ATP, as well as others), inorganic phosphates, calcium, and serotonin.
Dense granules
What do lysosomal granules contain?
Hydrolytic enzymes
Where does the dense tubular system originate from?
MK endoplasmic reticulum
What does the dense tubular system store?
Calcium and cyclooxygenase
What is the function of cyclooxygenase?
Converts arachidonic acid to unstable endoperoxide precursors of prostaglandins and thromboxane
______________ is a controlled process, that arrests vascular bleeding after an injury.
Haemostasis
A primary haemostatic plug is formed, which provides a surface for _________ generation and secondary haemostasis.
Fibrin
List two functions of haemostasis.
Promotes repair of injured tissues
Contributes to vascular integrity and vessel wall repair, following an injury
True or false: platelets contribute to innate and adaptive immunity.
True
Platelets in circulation are normally ________.
Inert
Platelets become ____________ after changes in normal environment that occurs post-injury.
Activated
List the four steps involved in platelet activation.
Adhesion
Aggregation
Shape change
Secretion
Describe adhesion.
Adhesion is initiated by exposure to subendothelial connective tissue, causing sticking to non-platelet surface
May adhere directly to collagen
Where shear rate is stronger, vWF and GPIb/IX receptors may be required
Very important for arterial thrombi
Explain aggregation.
The attachment of platelets to each other after stimulation
Fibrinogen can link platelets, because of its structure
Calcium is needed for platelet aggregation to occur (but not for adhesion)
Fibrinogen and calcium are found in plasma, and in high concentrations in platelet storage granules
Describe platelet shape change.
Occurs when the internal calcium reaches a certain level
Involves cytoskeletal proteins
Results in larger surface area that increases biochemical reactions and increases chances of contact with other platelets
Becomes irreversible when continued stimulation causes degranulation
Outline platelet secretion events.
Follows adhesion and shape change
An energy-dependent process
Occurs before or during platelet aggregation
Fusion of OCS with granules and release of granule contents through OCS, or fusion of granules with each other and with the plasma membrane, occurs
List four platelet-derived agonists.
ADP
Serotonin
Platelet-activating factor (PAF)
TXA2
Name three other agonists.
Collagen, thrombin, and epinephrine
True or false: collagen and thrombin are weak agonists.
False
Name three functions of strong agonists.
Can activate full range of platelet functions
Do not require cyclooxygenase activity
Release of ADP
List six weak agonists.
ADP
Epinephrine
TXA2
Serotonin
PAF
Vasopressin
What is the function of a weak agonist?
Initiates platelet activation
Outline the IP3-DAG pathway.
Involves activated phospholipase C
Cleavage of phosphatidyl inositol 4,5-bisphosphate (PIP2) to give diacylglycerol (DG) and inositol-1,4,5-triphosphate (IP3)
Ø Second messenger signals sent to cell interior
Calcium is released from DTS and influx from outside of the cell occurs
Describe the thromboxane pathway.
G-protein activation triggers the membrane enzyme phospholipase A2, which causes the release of arachidonic acid from membrane
Formation of thromboxane A2 (by cyclooxygenase and thromboxane synthase) occurs
List three features of thromboxane.
Stimulates secretion from platelet granules
Enhances vasoconstriction
Acts as a platelet agonist to continue activation process
The ________ pathway is inhibitory.
cAMP
What is the cAMP pathway?
An important negative regulator of platelet activation
List three factors inhibited by the cAMP pathway.
Shape change
Platelet secretion
Integrin activation, and the associated conversion of GPIIb/IIIa to active form
State six physiological controls of platelet activation.
Minimal platelet contact with agonists (endothelial cell barrier)
Dilutional effect of flowing blood
Limited platelet responsiveness to agonists (endothelial cell production of NO; PGI2 causes increased cAMP; ADPase; antithrombin)
Limited duration of agonist receptor activity (short half-life of agonists)
Maintenance of tight controls on cytosolic [Ca++]
Inability of ‘resting’ GPIlb/Illa to bind fibrinogen
Two-thirds of platelets circulate in ___________ ________.
Peripheral blood
Where are one-third of platelets sequestered?
Spleen
The body’s two platelet pools are in ___________ ____________.
Constant equilibrium
What is the reference range of the mean platelet volume?
~6.8–10.2 fL
An ____________ correlation between platelet count and mean platelet volume exists.
Inverse
The _______________ _____________ __________ is analogous to red cell distribution width.
Platelet distribution width
What is the reference range for platelet distribution width?
~9–15 fL
