Sections 1 and 2: Platelet Function

Question 1

Hemostasis definition

Answer 1

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

Question 2

Hemostasis involved parameters

Answer 2

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

Question 3

Abnormal bleeding vs abnormal clotting

Answer 3

hemorrhage and thrombosis

Question 4

Primary hemostasis

Answer 4

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

Question 5

Secondary hemostasis

Answer 5

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

Question 6

Fibrinolysis

Answer 6

Dissolves blood clots (initiation of wound healing)

Question 7

Hemarthralgia

Answer 7

Bleeding in joints

Question 8

Medical terms that mean bruise

Answer 8

• Purpura
• Ecchymoses
• Hematoma

Question 9

Epistaxis

Answer 9

Nose bleed

Question 10

List the 3 vascular layers from inside to outside

Answer 10

1. Tunica intima
2. Tunica media
3. Tunica adventia

Question 11

Tunica intima

Answer 11

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

Question 12

Tunica media

Answer 12

• Elastic tissue and smooth muscle
• Controls vasoconstriction and sometimes vasodilation

Question 13

Tunica adventia

Answer 13

Connective tissue support

Question 14

How does the vasculature prevent thrombus formation in hemostasis?

Answer 14

• 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

Question 15

List steps of general hemostasis when endothelial lining is disrupted

Answer 15

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

Question 16

Explain the first step of hemostasis, vasoconstriction

Answer 16

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

Question 17

Explain the second step of hemostasis: initial stimuli

Answer 17

• 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

Question 18

Explain the third step of hemostasis: localize clot formation

Answer 18

• 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

Question 19

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

Answer 19

• ECs secrete tissue plasminogen activator to facilitate clot breakdown

Question 20

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

Answer 20

formation, prevention, breakdown

Question 21

Thrombopoietin (TPO) function

Answer 21

• 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

Question 22

Explain how TPO levels relate to platelet levels

Answer 22

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

Question 23

Adhesion

Answer 23

Platelets stick to site of injury (exposed collagen)

Question 24

Aggregation

Answer 24

Platelets stick to other platelets (helps close physical gap)

Question 25

Platelet glycocalyx

Answer 25

- Outer layer (peripheral zone) - Mediates platelet adhesion and aggregation

Question 26

Platelet open canalicular system

Answer 26

- Peripheral zone, extension of platelet membrane - Channels of membrane wind into platelet so that stuff moves in and out

Question 27

Platelet cytoskeleton

Answer 27

- Sol-gel zone - Helps secretion process and structural integrity - Microfilaments made of actin and myosin

Question 28

Platelet dense tubule system

Answer 28

- Sol-gel zone - Plt activation and calcium storage/release

Question 29

Platelet dense granules

Answer 29

- 6 per plt - ADP, calcium, serotonin....etc

Question 30

Platelet alpha granules

Answer 30

- ~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)

Question 31

Explain how aspirin prevents plt activation/aggregation

Answer 31

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

Question 32

Explain how a platelet adheres to collagen

Answer 32

- Platelets can't directly stick to collagen, so use vWF as intermediate glue - vWF binds GP1b receptor on plt

Question 33

List steps of primary hemostasis

Answer 33

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

Question 34

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

Answer 34

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) 4. Plts aggregate via ADP and TXA2 5. Fibrinogen attaches to platelet membrane forming bridges between platelets resulting in a platelet plug (GPIIb/IIIa) 6. Actin and myosin contract to pull clot in tight and stop bleeding 7. Platelet plug gives foundation for clot formation

Question 35

Explain process of platelet shape change

Answer 35

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

Question 36

List granule contents and their roles

Answer 36

- Serotonin = vasoconstriction - vWF = plt adhesion - ADP and TXA2 = plt aggregation - Calcium = plt activation/coag cascade - Fibrinogen = plt aggreg/coag cascade

Question 37

How do ADP and TXA2 facilitate plt aggregation?

Answer 37

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

Question 38

Explain how platelet plug formation provides foundation for clot formation

Answer 38

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

Question 39

What is Platelet Factor 3?

Answer 39

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