Hemostasis

Question 1

Platelets (=thrombocytes) are cell fragments that are derived from what?

Answer 1

Megakaryocyte.

Question 2

Describe the production of platelets

Answer 2

Production of platelets is determined by TPO (thrombopoeitin). The liver and kidney are always secreting TPO. Platelets will destroy TPO by binding to to mpl receptor when we do not need to form anymore, preventing platelet production.

However, if we have a low platelet count= less TPO being destroyed= more TPO in the body–> TPO makes platelets.

Question 3

Amount of TPO in our body is controlled by what?

Answer 3

Platelets.

They have an inverse relationship in number.

Question 4

High number of platelets=

Answer 4

Lots bound to the mpl receptor on TPO

–> TPO internalized

–> TPO destroyed

–> less TPO to act on megakaryocytes and create platelets

Question 5

What cell lineages does TPO act on?

Answer 5

ALL

Question 6

What do platelets contain?

Answer 6

1. mT, which makes ADP and ATP
2. Actin and myosin, because they contract, causing the vesicles to empty
3. COX-1, makes thromboxane A2
4. Serotonin, a vasoconstrictor
5. Fibrin-stabilizing factor to help with clot stability
6. Platelet-derived growth factor to help with repair

Question 7

What would happen if there is a mutation on the TPO receptor on platelets?

Answer 7

Platelet cannot internalize and destroy TPO–>

–> Make too many platelets from megakaryocytes–>

Too many blood cells in our body (polycythemia vera)

Question 8

Describe the membranes of platelets?

Answer 8

The membranes have glycoproteins that, when activated, become sticky, phospholipids (factor 3, important to activate the clotting cascade) and collagen receptors.

Question 9

Effects of thrombopiesis?

Answer 9

Increases dividision and maturation of all blood cell lineages.

Question 10

What is hemostasis?

Answer 10

All of the steps taken to reduce blood loss.

Question 11

What are the 4 steps of hemostasis?

Answer 11

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

Question 12

What is vascular spasm?

Answer 12

Damaged vessel will loose blood. As a result, the smooth muscle in the vicinity will start to spasm to limit the blood flow loss.

Question 13

What are the causes of vascular spasm? (3)

Answer 13

1. Myogenic response–> vascular smooth m will detect damage and spasm. This does not involve neurons or reflexes
2. Platelets activate and secrete platelet factors such as 5-HT, thromboxane A2 which will cause vasoconstriction.
3. Neural reflex, however it is not necessary or suficient for spasm to occur

—-these mechanisms reduces blood loss by slowing or stopping blood flow out—-

Question 14

Formation of platelet plug

Answer 14

1. Damaged endothelium wall of the BV will expose collagen
2. von Willibrand Factor binds to the exposed collaged
3. Platelets bind to the vWBF, on the exposed collagen
4. Platelet activates, causing swelling and formation of podocytes
5. Platelet contracts, secreting [thromboxane A2, ADP, platelete derived growth factor (PDGF)]
6. Platelets stick to the vessel wall and each other d/t thromboxane A2 and ADP
7. Platelet plug is formed and stops small bleeds

Question 15

What is the coagulation cascade?

[picture]

Question 16

During blood coagulation, after we have the formation of our clot, what do we want to do?

Answer 16

We want to solidify the clot to get rid of excess fluid.

1. Fibrin polymers will bind to platelets

2. Ca2+ will cause the actin and myosin in the platelet to contract

Question 17

How do we repair our blood vessel?

Answer 17

PDGF (platelet-derived growth factor)

1. Form fibroblasts–>
2. Fibroblasts–> smooth muscle cells–>
3. Deposits collagen

Question 18

How do we get rid of the clot?

Answer 18

1. Thrombin binds into thrombomodulin, which turns thrombin into an anti-coagulant
2. Converts protein C–> activated protein C
3. Activated t-PA inhibitor –> [activated protein C]–> inactivated t-PA inhibitor
4. increase of t-PA
5. Increase of t-PA will cause [plasminogen–> plasmin]
6. Plasmin–> break down the fibrin (clot)

Question 19

Removal of the clot will, ultimately, rely on the activation of what?

Answer 19

Plasmin, which is found in the blood in an active form, plasminogen.

Question 20

What is t-PA?

Answer 20

Plasminogen activator

Question 21

What mechanisms prevent clotting? (5)

Answer 21

1. Smooth surface of blood vessels
2. Continous blood flow (not turbulent)
3. Platelet repelling action of glycocalynx
4. Fibrin, heparin, prostacyclin, anti-thrombin III
5. Protein C, when activated, inactivates factor 5 and 8

Question 22

How does heparin prevent clotting?

Answer 22

Heparin is a anti-coagulant.

Heparin binds anti-thrombin 3.

When bound, this will block 10a and 2a.

Question 23

How does Protein C prevent clots?

Answer 23

1. Thrombin binds to thrombomodulin
2. Activation of protein C
3. Protein C –> inactivate 5a and 8a.

Question 24

How does prostacucline and NO prevent clotting?

Answer 24

1. Vasodilation

2. Prevents the activation of platelets

Question 25

How can arthersclerosis increase risk of clotting?

Answer 25

Exposing platelets to a atherosclerotic plaque will cause the platelets to rupture, triggering activation of circulating platets and the clotting cascade as well.

Question 26

What is a **common "clot-buster"**?

Answer 26

TPA: Plasminogen--\> plasmin--\> **causes the lysis of fibrin**

Question 27

What is a Leidin mutation?

Answer 27

Activated factor 5 cannot be inacted by Protein C, forming inappropriate clots.

Question 28

What is responsible for the change in the platelet membrane that causes it to stick to damaged BV and other platelts?

Answer 28

**Thromboxane A2** **ADP**

Question 29

What is released from the platelet during vasvular spasm?

Answer 29

5HT Thromboxane A2 ---vasoconstriction----