Hemostasis

Question 1

What does TPO do?

Answer 1

• Actiavates production of platelets
• Binds to c-MPL on megakaryocytes and other hematopoeitic cells

Question 2

How is TPO secretion controlled?

Answer 2

• Controlled by itself and platelets themselves

Question 3

WHat happens to TPO if you have high # of platelets?

Answer 3

• TPO bounnd to c-MPL receptor, internalized, anddegraded in platelets and megakaryocytes
• Little TPO is free

Question 4

What happens to TPO if you have low number of platelets?

Answer 4

• Little TPO is bound to c-MPL receptor and is not ddegraded
• High TPO free

Question 5

What are the four steps to hemostasis?

Answer 5

1. Vasuclar spasm
2. Formation of platelet plug
3. Formation of blood clot
4. Repair of damage

Question 6

What is the purpose of vasospasm?

Answer 6

• Disrupsts blood flow to keep blood above the spasm and avoid further blood loss

Question 7

What factors cotnribute to the vasospasm?

Answer 7

• Myogenic
• Platelet factors-serotonin & thromboxane A2
• Release of molecules from endothelieal cells
• Neural reflex

Question 8

How does platelet plug adhesion occur

Answer 8

• Initiated by activation of latelet receptors such as glycoprotein Ib/Ia

Question 9

What are ligands for plateleet receptors?

Answer 9

• Von willebrand factor: released from endothelial cells and platelets
• Collagen (Gp Ia/IIa) fibronectin and laminin (Gp Ic/IIa) under the endothelial layer

Question 10

What happens after activation of platelet receptors?

Answer 10

• Activation of phospholipase C and Calciumm influx
• Release of ATP ADP serotonin and Ca from dense granules
• Release GF, vWF, factor V and fibrinogen from alpha granules
• Finger like filopodia extension
• Generation fo thromboxane A2 from archidonic acid by cyclooxgenase

Question 11

What does ADP bind?

Answer 11

• P2Y12 receptors on platelets which causes conformational change in Gp IIb/IIIa
• Now platelet can bind fibrinoge4n which forms aggregation of platelets allowing the platelet plug to form

Question 12

What does aspirin inhibit?

Answer 12

Its a cyclooxygenase inhibitor that inhibits clotting by reducing release of thromboxane A2

Question 13

Blood clot formation? Activation of prothrombin & Fibrinogen?

Answer 13

• Activated by factor 5 and Ca to Thrombin
• Generation of fibrin from fibrinogen
• Fibrin polymerization and contarction of clot (requires Ca)

Question 14

How does the vessel wall get repaired?

Answer 14

• Platelets secrete platelet derived growth factor which stimulates fibroblasts to grow into area and differentiate into smooth muscle

Question 15

How are clots broken down?

Answer 15

• Plasmin
• Activated by tissue plasminogen activator
• Resleased by damage tissue
• protein C inactivates inhibitior of t-PA
• Plasmin is responsible for lysis of clot