LG2.14 Introduction to Coagulation Part 1

Question 1

What are the 4 major events that occur in hemostasis?

Answer 1

1) Vasoconstriction
2) Platelet Actions: Adhesion, Activation, Release or Secretion, Aggregation
3) Fibrin Clot formation/coagulation
4) Fibrinolysis

Question 2

What is hemostasis?

Answer 2

Hemostasis is the process of normal blood clotting, the subsequent dissolution of the clot, and subsequent repair of the injured tissue.

Question 3

What are the major components of the hemostatic system?

Answer 3

a. Vascular endothelium
b. Platelets
c. Coagulation system
d. Fibrinolytic system

Question 4

What does Nitric Oxide do?

Answer 4

Inhibits platelet adhesion and aggregation by elevating levels of cGMP

Question 5

What does Prostacyclin do?

Answer 5

Inhibits platelet aggregation by increasing levels of cAMP

Question 6

What does Thrombomodulin do?

Answer 6

Binds thrombin which then cleaves protein C to yield activated protein C

Question 7

What substances does the Endothelial cells produce that are potent vasodilators and inhibitors of platelet functions?

Answer 7

• prostacyclin (prostaglandin I2, PGI2)

- nitric oxide (NO).

Question 8

What does Tissue Plasminogen activator (TPA) do?

Answer 8

Activates fibrinolysis

Question 9

What is Primary Hemostasis?

Answer 9

Formation of a Platelet Plug

Question 10

What is the steps of Primary hemostasis?

Answer 10

i. Platelet Adhesion
ii. Shape change
iii. Granule release (ADP,TXA2)
iv. Recruitment
v. Aggregation (hemostatic plug)

Question 11

What is secondary hemostasis?

Answer 11

Formation of a fibrin Clot

Question 12

What is the steps of secondary hemostasis?

Answer 12

i. Tissue factor
ii. Phospholipid complex expression
iii. Thrombin generation
iv. Fibrin polymerization

Question 13

What is Prothrombin converted to?

Answer 13

Thrombin

Question 14

What is thrombin covert?

Answer 14

Fibrinogen to Fibrin

Question 15

What is the function of vWF?

Answer 15

function is binding to other proteins, in particular factor VIII, and it is important in platelet adhesion to wound sites.[1]

Question 16

What does vWF stand for?

Answer 16

von Willebrand Factor

Question 17

What is the function of ADP?

Answer 17

A mediator of further platelet activation, leads to a conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrinogen

Question 18

What does TXA2 stand for?

Answer 18

Thromboxane A-2

Question 19

What is the function of TXA2?

Answer 19

A prostaglandin, Vasoconstriction

Question 20

What is Gp IIB/IIa?

Answer 20

• Is an integrin complex found on platelets. It is a receptor for fibrinogen[1] and von Willebrand factor and aids in platelet activation.
• The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence.
• Platelet activation by ADP leads to a conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrinogen.

Question 21

What is Fibrinogen?

Answer 21

Form bridges between platelets, by binding to their GpIIb/IIIa surface membrane proteins; however, its major function is as the precursor to fibrin

Question 22

What is PAI stand for?

Answer 22

Plasminogen activator inhibitor

Question 23

What is FDP stand for?

Answer 23

Fibrin degradation products

Question 24

What does t-PA stand for?

Answer 24

tissue plasminogen activator

Question 25

How is Plasminogen involved in clotting?

Answer 25

Plasminogen is a zymogen of plasmin. It is manufactured in the liver and circulates in the blood in a form that is activation-resistant. Upon binding to fibrin, it can readily be converted to plasmin by plasminogen activators

Question 26

What does activated GpIIb/IIa receptors provide?

Answer 26

The GpIIb/IIIa receptors on activated platelets form bridging crosslinks with fibrinogen, leading to platelet aggregation.

Question 27

What do alpha granules contain?

Answer 27

• α granules contain fibrinogen, clotting factors V and VIII

Question 28

What do dense bodies contain?

Answer 28

ADP, ionized calcium and serotonin

Question 29

How are platelets involved in clotting?

Answer 29

- Platelets are anucleate cell fragments shed into the bloodstream by marrow megakaryocytic. - They play a critical role in normal hemostasis by forming a hemostatic plug that seals vascular defects, and by providing a surface that recruits and concentrates activated coagulation factors.

Question 30

What do platelet receptos GP1a-IIa and GP VI bind directly to?

Answer 30

Subendothelial collagen

Question 31

What do platelets bind indirectly to collagen via GPib and vWF bind indirectly to?

Answer 31

Collagen/

Question 32

What is ECM?

Answer 32

Extracellular matrix

Question 33

What happens directly after vascular injury?

Answer 33

After vascular injury, platelets encounter ECM constituents (collagen is most important) and adhesive glycoproteins such as vWF. This sets in motion a series of events that lead to (1) platelet adhesion, (2) platelet activation and (3) platelet aggregation.

Question 34

What does activation of thrombin cause?

Answer 34

Activation of thrombin promotes fibrin deposition, cementing the platelet plug in place.

Question 35

Where does the conversion of prothrombin to thrombin occur?

Answer 35

-The conversion of prothrombin to thrombin usually takes place on anionic phospholipid membranes that are exposed on the activated platelet membrane.