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B-Haematology II > Platelets > Flashcards

Platelets Flashcards

1
Q

What are platelets?

A

Cellular fragments of megakaryocytes

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2
Q

True or false: platelets are anuclear.

A

True

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3
Q

Platelets are approximately _____ to four µm in diameter, but can be larger.

A

One

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4
Q

What is the platelet reference range?

A

150-400 x10^9/L

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5
Q

What is the in-vivo lifespan of platelets?

A

~10 days

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6
Q

Mean platelet volume (MPV) is useful, but less reliable than an MCV value, and is generally ≤___ fL

A

10

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7
Q

List the order
which proliferation and maturation of precursor megakaryocytes in bone marrow follows.

A

Common myeloid progenitor

Megakaryoblast progenitor

Megakaryoblast

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8
Q

List two cells of the megakaryocytic lineage.

A

Actively-proliferating progenitor cells

Post-mitotic (non-proliferating) megakaryocytes

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9
Q

What term is given to the process of platelet differentiation?

A

Endomitosis

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10
Q

______________ and release time is generally approximately four to seven days.

A

Proliferation

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11
Q

List six features of a megakaryoblast.

A

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

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12
Q

Describe a promegakaryocyte.

A

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

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13
Q

State five features of the mature megakaryocyte.

A

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

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14
Q

Platelets are released directly into the sinuses of the bone marrow, in groups called _______________.

A

Proplatelets

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15
Q

The __________ of megakaryocytes stay in the marrow and degenerate.

A

Nuclei

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16
Q

Two-thirds of released platelets enter circulation; the remainder are sequestered in the ___________.

A

Spleen

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17
Q

Platelet mass in circulating blood, and _____________ ________ in the marrow, stimulate production.

A

Megakaryocyte mass

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18
Q

__________, together with growth factors, promote progenitor cells.

A

Cytokines

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19
Q

What cytokines are used for platelet proliferation?

A

IL-3 and GM-CSF

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20
Q

List two cytokines involved in platelet maturation.

A

IL-6 and IL-11

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21
Q

_______________ (TPO) influences all stages of megakaryocyte production, independently or in synergy with cytokines.

A

Thrombopoietin

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22
Q

What organ constitutively produces thrombopoietin?

A

Liver

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23
Q

True or false: thrombopoietin and erythropoietin are not structurally related.

A

False

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24
Q

What is thrombopoietin’s receptor called, and where is it found?

A

CD110 (c-Mpl); found on circulating platelets and progenitors

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25
Q

Binding of TPO with platelet promotes _____________ of the platelet.

A

Activation

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26
Q

Low platelet count means more __________TPO, and this can stimulate progenitor cells to proliferate.

A

Free

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27
Q

TPO levels are regulated by platelet __________.

A

Mass

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28
Q

Upon binding to Mpl receptors on platelets, TPO is ________________________________________________________________________________.

A

Internalized and removed from circulation.

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29
Q

In the case of __________________, much TPO is removed from circulation, resulting in low levels of TPO signalling.

A

Thrombocytosis

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30
Q

During thrombocytopenia, little TPO is cleared from circulation, resulting in _________ ____________ of TPO signalling.

A

High levels

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31
Q

MK interact with ___________ ____________ cells.

A

Marrow stromal

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32
Q

Stromal cells produce positive and negative ______________ of MK growth.

A

Regulators

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33
Q

Stromal cells have ligands for __________ proteins, which influence lineage choice of MEP for RBCs or platelets.

A

Notch

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34
Q

What factor augments TPO?

A

Stromal cell-derived factor-1 (SDF-1)

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35
Q

MK is found primarily in vascular niche, physically attached to endothelial cells lining ___________ vessels.

A

Sinusoidal

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36
Q

Platelets are _______-shaped, with a flat surface.

A

Disc

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37
Q

Platelets repel each other and repel ___________ cells.

A

Endothelial

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38
Q

List three features or functions of the glycocalyx.

A

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

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39
Q

The ____________ ___________ is the former demarcation membrane of parent megakaryocyte.

A

Platelet membrane

40
Q

List four functions of platelets.

A

Adhesion

Secretion

Aggregation

Contraction

41
Q

Name and describe one system which the platelet membrane invaginates to form.

A

Open canicular system, that involves numerous invaginations of the platelet surface, and is a direct connection between the interior and surface of the platelet

42
Q

List two neutrally-charged platelet membrane phospholipids.

A

Phosphatidylcholine (PC)

Sphingomyelin

43
Q

PS and PE are ____________-charged platelet membrane phospholipids.

A

Negatively

44
Q

True or false: arachidonic acid is not found in platelet membranes.

A

False

45
Q

Outline the events and features of the inactive resting membrane state of platelets.

A

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.

46
Q

The inactive membrane resting state is essential to ____________ haemostasis.

A

Secondary

47
Q

GP-Ib/IX/V bind to VWF, __________, and ristocetin.

A

Thrombin

48
Q

GP-Ib/IX/V involve primary ______________ receptors.

A

Adhesion

49
Q

GP-IIb/IIIa (CD41/61) bind to _______________ and VWF.

A

Fibrinogen

50
Q

GP-IIb/IIIa (CD41/61) involves primary ______________ factors.

A

Aggregation

51
Q

GP-Ia/IIa (CD49b/CD29) bind to _____________.

A

Collagen

52
Q

GP VI (in complex with ________) binds to collagen.

A

FcRy

53
Q

List two substances to which GP-IV (CD36) binds.

A

Collagen and thrombospondin

54
Q

List three functions of the platelet’s structural zone.

A

Structural support for the platelet

Maintains discoid shape in the resting state

Allows the cell to change shape when activated

55
Q

______________ (composed of tubulin), and a network of proteins (actin, actin-binding protein, and several other proteins) make up the cytoskeleton.

A

Microtubules

56
Q

List three components of the organelle zone of platelets.

A

Mitochondria

Granules

Glycogen particles

57
Q

True or false: the organelle layer lies above the microtubules.

A

False

58
Q

Identify the four types of platelet granules.

A

Dense bodies

Alpha

Lysosomal

Microperoxisomes

59
Q

___________ are storage sites for proteins, and other substances necessary for platelet function.

A

Granules

60
Q

List four major features of alpha granules.

A

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

61
Q

_____________ __________ contain mediators of platelet function and haemostasis, such as nucleotides (ADP, ATP, as well as others), inorganic phosphates, calcium, and serotonin.

A

Dense granules

62
Q

What do lysosomal granules contain?

A

Hydrolytic enzymes

63
Q

Where does the dense tubular system originate from?

A

MK endoplasmic reticulum

64
Q

What does the dense tubular system store?

A

Calcium and cyclooxygenase

65
Q

What is the function of cyclooxygenase?

A

Converts arachidonic acid to unstable endoperoxide precursors of prostaglandins and thromboxane

66
Q

______________ is a controlled process, that arrests vascular bleeding after an injury.

A

Haemostasis

67
Q

A primary haemostatic plug is formed, which provides a surface for _________ generation and secondary haemostasis.

A

Fibrin

68
Q

List two functions of haemostasis.

A

Promotes repair of injured tissues

Contributes to vascular integrity and vessel wall repair, following an injury

69
Q

True or false: platelets contribute to innate and adaptive immunity.

A

True

70
Q

Platelets in circulation are normally ________.

A

Inert

71
Q

Platelets become ____________ after changes in normal environment that occurs post-injury.

A

Activated

72
Q

List the four steps involved in platelet activation.

A

Adhesion

Aggregation

Shape change

Secretion

73
Q

Describe adhesion.

A

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

74
Q

Explain aggregation.

A

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

75
Q

Describe platelet shape change.

A

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

76
Q

Outline platelet secretion events.

A

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

77
Q

List four platelet-derived agonists.

A

ADP
Serotonin
Platelet-activating factor (PAF)
TXA2

78
Q

Name three other agonists.

A

Collagen, thrombin, and epinephrine

79
Q

True or false: collagen and thrombin are weak agonists.

A

False

80
Q

Name three functions of strong agonists.

A

Can activate full range of platelet functions
Do not require cyclooxygenase activity
Release of ADP

81
Q

List six weak agonists.

A

ADP
Epinephrine
TXA2
Serotonin
PAF
Vasopressin

82
Q

What is the function of a weak agonist?

A

Initiates platelet activation

83
Q

Outline the IP3-DAG pathway.

A

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

84
Q

Describe the thromboxane pathway.

A

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

85
Q

List three features of thromboxane.

A

Stimulates secretion from platelet granules
Enhances vasoconstriction

Acts as a platelet agonist to continue activation process

86
Q

The ________ pathway is inhibitory.

A

cAMP

87
Q

What is the cAMP pathway?

A

An important negative regulator of platelet activation

88
Q

List three factors inhibited by the cAMP pathway.

A

Shape change

Platelet secretion

Integrin activation, and the associated conversion of GPIIb/IIIa to active form

89
Q

State six physiological controls of platelet activation.

A

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

90
Q

Two-thirds of platelets circulate in ___________ ________.

A

Peripheral blood

91
Q

Where are one-third of platelets sequestered?

A

Spleen

92
Q

The body’s two platelet pools are in ___________ ____________.

A

Constant equilibrium

93
Q

What is the reference range of the mean platelet volume?

A

~6.8–10.2 fL

94
Q

An ____________ correlation between platelet count and mean platelet volume exists.

A

Inverse

95
Q

The _______________ _____________ __________ is analogous to red cell distribution width.

A

Platelet distribution width

96
Q

What is the reference range for platelet distribution width?

A

~9–15 fL

B-Haematology II (2 decks)

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