Hemostasis

Question 1

Platelets are derived from

Answer 1

GM-CSF thrombo
—> Megakaryocytes*
*hematopoietic linaege

Question 2

Another name for platlets

Answer 2

Thrombocytes

Question 3

When are platelets formed

Answer 3

They are active when they a fragments off the megakaryocytes

Question 4

Normal levels of platelets

Answer 4

150,000-450,000 ul^3

Question 5

What do platelets contain

Answer 5

Actin, myosin, thrombostatin, mitochondria, peroxioomes, COX2, Fribrin
2 granules

Question 6

2 granules that platelets have

Answer 6

1. a-granules : store Von Willebrand factor, fibrinogen, factor 5 (clotting)
2. dense-core granules : store ATP, ADP, HT’5, Ca+2

Question 7

Megakaryocytes and platelets take up what

Answer 7

Fibrinogen that they secrete in the liver for Hemostasis

Question 8

3 steps for platelets

Answer 8

Adhesion
Activation
Aggregation

Question 9

What regulates platelet formation

Answer 9

Thrombopoietin (TPO) made in liver and kidney
The C-terminal if it prolongs life of platelet
* increase production and function of hematopoietic stem cells and platelets

Question 10

How does TPO act

Answer 10

It binds to the c-MPL (CD110) receptor on the Megakaryocytes

Question 11

Low platelet count effect on TPO

Answer 11

High free TPOs

C-MPL is not internalized and degraded

Question 12

High platelet count effect on TPO

Answer 12

Low free TPOs and c-MPL receptor is internalized and degraded

Question 13

4 steps to healing injury

Answer 13

1. Vascular Spasm : severed vessel
2. Formation of platelet plug : Platelet agglutinate + fibrin appears
3. Formation of blood clot
4. Repair of Damage : clot retracts

Question 14

What is vasospasm

Answer 14

Disrupt BF and keep it above the injury = avoid more blood loss

Question 15

4 things that contribute to vasospasm

Answer 15

1. Myogenic : reflex from damage to SM
2. Platelet factor : serotonin, thromboxane A2
3. Release of molecules from endothelial BV cells
4. Neural reflex from pain or injury

Question 16

How do platelets bind to the vessels

ADHESION

Answer 16

The platelets have glycoproteins

1. Von Willebrand factor is released from endothelial cells —> GP 1b/a on platelet
2. Injured endothelial cells expose collagen —> GP 1a/2a on platelet
3. Laminitis and fibronectin is also exposed —> GP 1c/2a on platelet

Question 17

What regulates adhesion of platelets

Answer 17

Negative charges and collagen on the surface

Question 18

What activates the platelet

Answer 18

When the GP are bound on its surface

Question 19

3 names for Von Willebrand disease

Answer 19

Psudohemophilia
Vascular hemophilia
Angiohemophilia

Question 20

What happens after the GP receptors of the platelet are activated

Answer 20

1. Phospholipase C is activated
2. CA+2 influx
3. = causes ATP, ADP, CA+2, HT’5 release from DENSE granules (inside platelet)
   = a-granules release vWF, Factor 5, Fibrinogen, GFs
4. Finger like filopodia extensions
5. Arachidonic acid—> Thromboxane A2 (by cyclooxgenase)

Question 21

cyclooxgenase

Answer 21

Converts aracidonic acid —> Thromboxane A2

Question 22

How do platelets aggregate

Answer 22

1. ADP is released : —> bind to P2Y12 on other platelets
2. HT’5 + thromboxane A2 activate other platelets also
3. Fibrinogen activates another platelet and causes bridges between platelets = PLATELET PLUG

Question 23

Aspirin on platelet aggregation

Answer 23

Inhibits cyclooxygenase

—I clotting (low thromboxane A2)

Question 24

Clopidogrel (plavix) on platelet aggregation

Answer 24

Inhibits P2Y12 receptors = no further platelet activation and no aggregation

Question 25

What makes one platelet able to bind to fibrinogen

Answer 25

Conformational change of the GP 2b/3a receptor of the platelet = allows fro bridges and forms platelet plug

Question 26

3 steps in making a clot

Answer 26

1. Prothrombin —> thrombin (by pro thrombin activator) 2. Fibrinogen —> fibrin (by thrombin) 3. Fibrin polymerizes and makes clot (uses CA+2)

Question 27

How does the vessel wall finally get repaired

Answer 27

PDGF (platelet derived GF) secreted by platelet | = allows fibroblasts to grow into the area and differentiate to SM and other cells needed

Question 28

How to remove clots

Answer 28

PLASMIN = lysis fibrin + fibrinogen

Question 29

How is plasmin made

Answer 29

1. Protein C —>> activated Protein C (by thrombin from endothelial cells) 2. Activated Protein C —> inactivates t-PA inhibitor (plasminogen activator) = PA can be made now 3. Plasminogen —> PLASMIN 4. Lysis of fibrins

Question 30

Protein C inactivated what 3 things

Answer 30

1. T-PA inhibitor 2. Factor 5a 3. Factor 8a

Question 31

4 anticoagulants made by body

Answer 31

1. Fibrin : ——I thrombin 2. Prostacyclin (PG12) : —> vasodilation and X aggregation of P 3. Antithrombin 3 : binds to thrombin to inhibit coagulation 4. Heparin : from mast cells to increase anti-thrombin function