Sections 1 and 2: Platelet Function Flashcards

1
Q

Hemostasis definition

A

Process of blood clotting to arrest bleeding and re-establishment of blood flow during the healing process

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2
Q

Hemostasis involved parameters

A
  • vascular
  • platelets
  • fibrin clot formation- coag cascade
  • control (inhibitory systems)
  • fibrinolysis
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3
Q

Abnormal bleeding vs abnormal clotting

A

hemorrhage and thrombosis

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4
Q

Primary hemostasis

A
  • Platelet aggregation (form platelet plug)
  • Capillaries
  • White thrombus forms
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5
Q

Secondary hemostasis

A
  • Fibrin strands form to strengthen platelet plug and RBCs get caught in mesh
  • Arteries/bigger vessels
  • Red thrombus
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6
Q

Fibrinolysis

A

Dissolves blood clots (initiation of wound healing)

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7
Q

Hemarthralgia

A

Bleeding in joints

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8
Q

Medical terms that mean bruise

A
  • Purpura
  • Ecchymoses
  • Hematoma
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9
Q

Epistaxis

A

Nose bleed

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10
Q

List the 3 vascular layers from inside to outside

A
  1. Tunica intima
  2. Tunica media
  3. Tunica adventia
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11
Q

Tunica intima

A

Layers of broad flat endothelial cells with underlying basement membrane - collagen

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12
Q

Tunica media

A
  • Elastic tissue and smooth muscle
  • Controls vasoconstriction and sometimes vasodilation
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13
Q

Tunica adventia

A

Connective tissue support

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14
Q

How does the vasculature prevent thrombus formation in hemostasis?

A
  • Provides physical barrier of endothelial cells covering basement membrane to prevent blood, platelets, and clotting factors from sticking
  • Endothelial cells generate PGI2 (Prostacylin) and nitric oxide, which causes vasodilation and inhibits platelet adhesion to those cells
  • Vasculature involved in activity of Protein C (thrombomodulin) and anti-thrombin (heparan)
  • Tissue factor pathway inhibitor (TFPI) inhibits Tissue Factor/Factor VIIa complex
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15
Q

List steps of general hemostasis when endothelial lining is disrupted

A
  1. Vasoconstriction
  2. Initial stimuli of hemostasis
  3. Localize clot formation
  4. Provide activators for clearance of thrombus to break down fibrin clot
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16
Q

Explain the first step of hemostasis, vasoconstriction

A
  • Blood flow slows such that platelets and coag factors easily attach to site of injury
  • Shear stress pushes platelets to vessel periphery (injury site)
17
Q

Explain the second step of hemostasis: initial stimuli

A
  • Damaged endothelial cells release platelet activating factor (PAF) to activate even more platelets
  • Tissue Factor III released (present in all tissues)
  • Collagen is exposed such that platelets adhere to it
18
Q

Explain the third step of hemostasis: localize clot formation

A
  • Endothelial cells synthesize and release von Willebrands factor for platelet adhesion, as well as secrete ADAMTS13 to chop up vWF
  • Binding sites for coag factors IXa and Xa
19
Q

Explain the fourth step of hemostasis: provide activators for clearance of thrombus to break down fibrin clot

A
  • ECs secrete tissue plasminogen activator to facilitate clot breakdown
20
Q

Fill in the blank
ECs play a role in _________, ________, and _______ of the clot

A

formation, prevention, breakdown

21
Q

Thrombopoietin (TPO) function

A
  • Regulates megakaryocyte production and platelet release from the BM in response to thrombocytopenia
  • Inhibits megakaryocyte apoptosis
  • Binds receptors on circulating platelets and BM megakaryocytes, gets internalized, and degraded
22
Q

Explain how TPO levels relate to platelet levels

A
  • More platelets means less TPO (gets destroyed), so fewer megakaryocytes
  • Fewer platelets means more TPO, so more megakaryocytes
23
Q

Adhesion

A

Platelets stick to site of injury (exposed collagen)

24
Q

Aggregation

A

Platelets stick to other platelets (helps close physical gap)

25
Q

Platelet glycocalyx

A
  • Outer layer (peripheral zone)
  • Mediates platelet adhesion and aggregation
26
Q

Platelet open canalicular system

A
  • Peripheral zone, extension of platelet membrane
  • Channels of membrane wind into platelet so that stuff moves in and out
27
Q

Platelet cytoskeleton

A
  • Sol-gel zone
  • Helps secretion process and structural integrity
  • Microfilaments made of actin and myosin
28
Q

Platelet dense tubule system

A
  • Sol-gel zone
  • Plt activation and calcium storage/release
29
Q

Platelet dense granules

A
  • 6 per plt
  • ADP, calcium, serotonin….etc
30
Q

Platelet alpha granules

A
  • ~55 per plt, more numerous than dense granules and give visual texture on Wright stain
  • TXA2, vWF, FV, FVIII, FI, HMWK, PF4, plasminogen, PAI-1…etc)
31
Q

Explain how aspirin prevents plt activation/aggregation

A

Aspirin inhibits cyclooxygenase-1 such that thromboxane A2 can’t be formed

32
Q

Explain how a platelet adheres to collagen

A
  • Platelets can’t directly stick to collagen, so use vWF as intermediate glue
  • vWF binds GP1b receptor on plt
33
Q

List steps of primary hemostasis

A
  1. Platelet adhesion
  2. Shape change
  3. Plt aggregation
  4. Secretion
  5. Primary hemostatic plug formed
34
Q

Explain the process of platelet activation from start to finish of clot

A
  1. Plt adheres to collagen via vWF binding GP1b receptor
  2. Adhesion initiates a shape change to allow granular content secretion (serotonin, vWF, ADP…etc)
  3. Plts aggregate via ADP and TXA2
  4. Fibrinogen attaches to platelet membrane forming bridges between platelets resulting in a platelet plug (GPIIb/IIIa)
  5. Actin and myosin contract to pull clot in tight and stop bleeding
  6. Platelet plug gives foundation for clot formation
35
Q

Explain process of platelet shape change

A
  1. Agonist (collagen/PAF)
  2. Pseudopods develop on plt surface that contain actin and myosin
  3. Microtubule circumferential ring contracts
  4. Membrane phospholipids activated
  5. Glycoprotein IIb/IIIa receptors appear
  6. Internal biochemical changes occur
  7. Granule secretion
36
Q

List granule contents and their roles

A
  • Serotonin = vasoconstriction
  • vWF = plt adhesion
  • ADP and TXA2 = plt aggregation
  • Calcium = plt activation/coag cascade
  • Fibrinogen = plt aggreg/coag cascade
37
Q

How do ADP and TXA2 facilitate plt aggregation?

A

They expose the GPIIb and IIIa complex, which enables fibrinogen to come bind and crosslink plts for aggregation

38
Q

Explain how platelet plug formation provides foundation for clot formation

A

Platelet Factor III (PF3) moves to outer surface of plt membrane to provide binding site for Vitamin K-dependent factors to support coag cascade

39
Q

What is Platelet Factor 3?

A

It’s the whole entire primary hemostatic complex! It provides a phospholipid-rich surface to support the coag cascade