Lecture 27: Hemostasis and Clotting Cascade

Question 1

What is the normal platelet count?

When is it too low and life threatening?

Answer 1

150k - 450k

<50 k is too low, <10k is life threatening

Question 2

What regulates production of platelets?

Where is it produced? What does it do?

Answer 2

TPO (Thrombopoietin)
Kidney and liver
Binds on c-MPL/CD110 and increases rate of HSC differentiation and maturation = more platelets

Question 3

How does the level of TPO in the blood relate to the number of platelets?

Answer 3

Inversely proportional. TPO binds platelets, so the more platelets in the blood, the more TPO is endocytosed and degraded = low blood concentration.

Question 4

What are the 4 steps of hemostasis?

Answer 4

1. Vascular spasm
2. Platelet plug formation
3. Blood clot formation
4. Endothelium damage repair

Question 5

What is a vasopasm?

Answer 5

Vasculature muscle spasms/narrows to block the flow downstream and prevent further loss of blood

Question 6

What can cause a vasospasm?

Answer 6

Myogenic (injury) response, platelet factors, release of molecules from endothelium

Question 7

What is necessary to form a platelet plug?

Answer 7

Platelet receptors have to be activated

Question 8

What happens in the local circulation when there is vascular injury?

Answer 8

Negative charges are exposed on collagen and laminin who can now bind their receptors on the platelets cell membrane and adhere to the vascular wall

Question 9

What are some examples of ligands that platelet receptors can bind?

Answer 9

vWF, collagen, fibronectin, laminin

Question 10

How does platelet activation lead to the activation of more platelets?

Answer 10

Platelet receptor binds ligand > PLC activation > Ca2+ influx > dense granules and alpha granule release various ligands from the subendothelium > ligands (particularly ADP, thromboxane A 2 and serotonin) activate receptors on other platelets > allows more platelets to bind fibrinogen that will allow platelets to aggregate with each other

Question 11

What else is generated from the process of platelet activation?

Answer 11

Arachidonic acid is converted into thromboxane A2 by cyclogenase

Question 12

How does aspirin work?

How does Plavix work?

Answer 12

• inhibits cyclogenase > decreases A2 release > decreases clotting
• inhibits P2Y12 receptors that bind ADP > inhibits platelet activation and aggregation

Question 13

How does a clot form?

Answer 13

Thrombin activation > increase in synthesis of fibrin and fibrin stabilizing factor > fibrin polymerization (requires Ca2+)

Question 14

How do platelets play a role in repairing vessel wall damage?

Answer 14

Platelets secrete growth factor > activates fibroblasts to grow and differentiate to rebuild damaged tissue

Question 15

What does plasmin do?

Answer 15

Lyses fibrin and fibrinogen thus lysing the blood clot

Question 16

How is plasmin synthesized?

Answer 16

Made in liver as plasminogen > activated by tissue plasminogen activator > active form is released by damaged tissue

Question 17

How can Protein C stop coagulation?

Answer 17

It inactivates the inhibitor of the t-PA, allowing plasmin to stay active to lyse clots

Question 18

How do these anticoagulants accomplish their tasks? 
Fibrin
Prostacyclin
Antithrombin II
Heparin

Answer 18

• inhibits thrombin
• vasodilation, limits platelet aggregation
• binds thrombin preventing it from forming clots
• increases anti-thrombin efficacy