Hemostasis

Question 1

What are the 4 steps of hemostasis?

Answer 1

1. Vascular spasm
2. Platelet plug formation
3. Blood clot formation
4. Repair of damage

Question 2

What are platelets also known as?

Answer 2

Thrombocytes

Question 3

What are platelets?

Answer 3

Cell fragments derived from megakaryocytes

Question 4

What are normal, bad and lethal levels of platelets?

Answer 4

Normal: 150k - 450 k

Bad: <50k

Lethal: <10k

Question 5

What does COX1 do in platelets?

Answer 5

Generates thromboxane A2

Question 6

What is the function of platelets?

Answer 6

Plugs small holes thru a highly controlled process of adhesion, activation and aggregation

Question 7

What is the production of platelets controlled by?

Answer 7

Controlled by Thrombopoietin (TPO)

Question 8

What Thrombopoietin (TPO)?

Answer 8

Peptide hormone w/ a N terminus similar to EPO and a C-terminus that prolongs its half life

Question 9

Where is TPO produced?

Answer 9

Kidney, liver

Question 10

What does TPO do?

Answer 10

Increases differentiator and maturation rate of heamtopoietic stem cells

Results in more megakaryocytes and platelets

Question 11

How does TPO activate the production of platelets?

Answer 11

Binds to c-MPL r. On megakaryocytes

Question 12

What are the feedback mechanisms working on TPO ?

Answer 12

High # of platelets —> TPO-c-MPL complex will be internaled and degraded

Low # of platelets —> little TPO Indus to c-MPL and not be degraded —> leaves HIGH level of FREE TPO

Question 13

What does vascular spasm do?

Answer 13

Disrupt blodo flow to keep blood above the spasm and avoid further blood loss

Question 14

What are the contributing factors to vascular spasm? (4)

Answer 14

1. Myogenic
2. Platelet factors
3. Release of molecules from endothelial
4. Neural reflex (not necessary or sufficient)

Question 15

What are the platelet factors that contribute to vascular spasm?

Answer 15

Serotonin, thromboxane A2

Question 16

What are the 3 steps needed to forming platelet plus?

Answer 16

1. Adhesion
2. Activation
3. Aggregation

Question 17

Where does adhesion for the platelet plug occur?

Answer 17

On cell membrane

• w/ glycoproteins 1b/1a and phospholipids
• w/ receptors for collagen and laminin
• w/ receptors for released signal molecules

Question 18

How do receptors regulate the when and where of adhesion for the platelet plug?

Answer 18

When = neg. charges or collagen and laminin are exposed

Where = at site of injury

Question 19

What are the ligands that will bind to Glycoproteins 1a/1b for adhesion of the platelet plug?

Answer 19

• von willebrand factor (vWF)

- collagen, fibronectin, laminin

Question 20

What releases von willebrand factor?

Answer 20

Released form endothelial cells and platelets themselves

Question 21

Where will collagen, fibronectin and laminin be for the adhesion of the platelet plug?

Answer 21

Under endothelial layer

Question 22

What does the activation of the platelet receptors do for the formation of the platelet plug?

Answer 22

Will activate Phospholipase C and allow calcium influx

Question 23

What do dense granules release during the activation phase of platelet plug formation?

Answer 23

Will release

• atp
• adp
• serotonin
• calcium

Question 24

What do Alpha granules release during the activation phase of platelet plug formation?

Answer 24

Release

• GFs
• vWF
• Factor 5
• fibrinogen

Question 25

What will be generated rom arachidonic acid by cyclooxygenase during activation phase of platelet plug formation?

Answer 25

Thromboxane A2

Question 26

What is released to promote aggregation of Platelets?

Answer 26

Release of 1. Adp 2. Serotonin 3. Thromboxane A2 -activates additional platelets —> promotes aggregation

Question 27

Where will ADP bind to on platelet?

Answer 27

To P2Y12 Rs.

Question 28

What will platelet receptors bind upon activation?

Answer 28

Fibrinogen

Question 29

What will fibrinogen do?

Answer 29

Form bridges b/w platelets and participate in forming platelet plug

Question 30

How does Aspring inhibit clotting?

Answer 30

Reduces release of thromboxane A2 bc it is a cyclooxygenase inhibitor

Question 31

How does Clopidogrel inhibit platelet plug formation?

Answer 31

Inhibits P2Y12 Rs. Blocks further platelet activation & aggregation (Antiplatelet Agent)

Question 32

What will activated thrombin generate?

Answer 32

Fibrin and fibrin stabilizing factor

Question 33

What will the polymerization of fibrin do? What does it require?

Answer 33

Will contract clot Requires calcium

Question 34

What will platelets do after ring replaced w/ thrombin and fibrin ?

Answer 34

Secreted platelet derived gf

Question 35

What is the role of platelet derived growth factor in healing?

Answer 35

Stimulates fibroblasts to grow into area nad differentiate into Sm. M., collagen etc.

Question 36

How are clots removed?

Answer 36

Via plasmin - will lyse fibrin and fibrinogen

Question 37

Where is plasminogen made? How is it activated? What releases it?

Answer 37

Made in over Activated by Tissue plasminogen activator (t-PA) Released by Damaged tissue

Question 38

What can inactivate t-PA?

Answer 38

Protein C

Question 39

What are chemicals that can limit clotting?

Answer 39

1. Fibrin (neg. feedback to inhibit thrombin) 2. Prostacyclin (PG12) -vasodilates and limits platelet aggregation 3. Antithrombin 3 (will bind w/ thrombin and form anticoagulant) 4. Heparin (increases anti-thrombin efficacy)

Question 40

What makes Prostacyclin (PG12)

Answer 40

Injured endothelial cells

Question 41

What is heparin derived form?

Answer 41

From mast cells