WEEK 2: HEMOSTASIS AND COAGULATION

Question 1

What is hemostasis?

Answer 1

Stop bleeding from an injured vessel.

Question 2

State the 3 components that are involved in hemostasis.

Answer 2

Blood vessel wall
Platelets
Plasma factors: Coagulation factors, anti-coagulation factors
Fibrinolytic factors

Question 3

Describe the two types of hemostasis.

Answer 3

PRIMARY HEMOSTASIS: Complex defense reaction which involves platelets and vessel wall.

Vasoconstriction and Platelet aggregation.

SECONDARY HEMOSTASIS
Proteolytic cleavage of plasma factors forming BLOOD CLOT.

Question 4

What is blood clotting?

Answer 4

Transformation of blood from into a solid gel consisting mainly of fibrin.

Question 5

Describe the endothelial cells

Answer 5

*They form the inner coating of vessel wall.
*They have an anti-platelet and anti-coagulant function.

Question 6

Describe the anti-platelet function of endothelial cells.

Answer 6

They release prostacyclin and nitric oxide which induce relaxation of perivascular smooth muscles which inhibit platelet aggregation.

Question 7

Describe the anti-coagulant role of endothelial cells.

Answer 7

*They release Thromboxane A2: Platelet activator and vasoconstriction.

*Von Willebrand factor: The most adhesion molecules of platelets.

Question 8

Outline the 2 main events of primary hemostasis.

Answer 8

1.Vasular spasm
2.Platelet plug formation

Question 9

Describe what happens in vascular spasm process of primary hemostasis.

Answer 9

*There is narrowing of blood vessels caused by persistent contraction

-This reduces blood flow through an injured vessel and minimize blood loss.

Question 10

Describe the process of platelet plug formation.

State the function of ADP and Thromboxane A2 released by activated platelets.

Answer 10

1.Platelet adhesion

*Von Willebrand factor bind to the exposed collagen and the platelets adhere to the binding sites on the vWF.
*The hemostatic foundation of platelet plug is formed.

2.Platelet activation and aggregation

*Collagen activates the platelets.

*Platelets change from their normal disc shaped with smooth surface to SPICKY PROCESSES WHICH HELP THEM ADHERE TO THE COLLAGEN AND OTHER PLATELETS.

3.Platelet aggregation.
*Activated platelets release ADP and Thromboxane A2.

ADP: Causes the surface of nearby circulating platelets to become sticky and adhere to first layer of aggregated platelets.

Thromboxane A2: Directly promote platelet aggregation.
*Enhances it indirectly by triggering the release of more ADP from platelet granules.

Question 11

Why does the platelet plug not continue to form on the adjacent normal vessel lining?

Answer 11

ADP stimulates release of PROSTACYCLIN and NITRIC OXIDE from the adjacent normal endothelium which inhibit platelet aggregation.

Question 12

State the main events in secondary hemostasis.

Answer 12

1.Clot formation
2.Clotting cascade

Question 13

What are the events of clot formation?

Answer 13

To convert fibrinogen to fibrin which is catalyzed by Thrombin.

Fibrin-stabilizing factor, factor XIII then stabilizes the fibrin mesh.

The clotting cascade helps in the conversion of prothrombin into thrombin which is used in clot formation.

Question 14

What is a clotting cascade?

Answer 14

Sequential reactions of specific factors in the clotting sequence with the aim of activating prothrombin into thrombin.

Question 15

State the 2 pathways of the clotting cascade.

Answer 15

Intrinsic pathway
Extrinsic pathway

Question 16

State the difference between the intrinsic pathway and extrinsic pathway.

Answer 16

INTRINSIC PATHWAY
*Slow
*Precipitates clotting within the blood vessel and blood samples in test tubes
*Factor VIII, IX and XII involved.
*Activated by internal trauma

EXTRINSIC PATHWAY
*Fast
*Precipitates clotting in damaged external surface
*Factor VII involved
*Activated by external trauma

Question 17

Name the pathway that combine both the intrinsic and extrinsic pathway.

Where does it combine the 2?

Answer 17

The common pathway.

At the activation of factor X

Question 18

State the names for all the factors of the clotting cascade.

Answer 18

Factor I: Fibrinogen
Factor 2: Prothrombin
Factor 3: Tissue thromboplastin
Factor 4: Calcium ion
Factor 5: Labile factor
Factor 6: UNASSIGNED
Factor 7: Stable factor
Factor 8: Antihemophilic factor
Factor 9: Christmas factor
Factor 10: Stuart factor
Factor 11: Plasma thromboplastin antecedent
Factor 12: Hageman factor
Factor 13; Fibrin stabilizing factor

Question 19

Outline the clotting cascade.

Question 20

Outline the roles of thrombin.

Answer 20

*Stimulate the conversion of fibrinogen into fibrin.
*It activates factor XIII which stabilizes fibrin meshwork of the clot.
*It enhances the activation of prothrombin via negative feedback.
*It enhances platelet aggregation
*Through positive feedback , platelets secrete PF3 , which stimulates the clotting cascade that results in thrombin activation.

Question 21

What is clot retraction?
Describe what happens in clot retraction.

Answer 21

*Clot retraction is the process of shrinking a blood clot over a number of days, which brings the edges of the blood vessel wall at the point of injury together to repair the damage.

Platelets shrink the fibrin mesh, pulling the edges of the damaged vessels closer together.

Fluid is squeezed from the clot.

Question 22

Describe vessel repair.

Answer 22

The aggregated platelets secrete a chemical that helps promote the invasion of fibroblasts from the surrounding connective tissue into the wound area of the vessel.

Fibroblasts form a scar at the vessel defect.

Question 23

Describe clot dissolution.

What are the 2 products obtained from fibrin dissolution?

Answer 23

Plasminogen is converted to plasmin bt tissue thromboplastin which was trapped in the clot.

Fibrin dissolves and slowly, the fibrins dissolve into fibrinogen and D-dimer.

Question 24

How the body prevent inappropriate clot formation.

Answer 24

Tissue plasminogen activator quickly activates plasmin to dissolve any small amount of fibrinogen converted to fibrin in absence of any wound.

Question 25

Define the following terms.
*Thromboembolism
*Thrombus
*Embolus

Answer 25

1.Blockage of blood vessel by a thrombus.

2.An abnormal intravascular clot attaches to a vessel wall.

3.Free floating clot.

Question 26

State factors that contribute to thromboembolism.

Answer 26

1.Roughened blood vessel wall associated with atherosclerosis

2.Imbalance in the clotting -anticlotting systems

3.Slow moving blood, small quantity of fibrin accumulates in stagnant blood.

4.Widespread clotting triggered by tissue thromboplastin.

5.Septic shock: Bacteria or tissues initiate clotting.

Question 27

State factors that contribute to thromboembolism.

Answer 27

1.Roughened blood vessel wall associated with atherosclerosis

2.Imbalance in the clotting -anticlotting systems

3.Slow moving blood, small quantity of fibrin accumulates in stagnant blood.

4.Widespread clotting triggered by tissue thromboplastin.

5.Septic shock: Bacteria or tissues initiate clotting.

Question 28

what is hemophilia??

What causes hemophilia?

Answer 28

Excessive bleeding disorder.
.
Platelet and vitamin K deficiency

Question 29

What is the role of vitamin K in blood clotting?

Answer 29

It is used for the synthesis of coagulation factors II, VII, IX,X.

(1972)

It also synthesizes Protein C and Protein S and Protein Z , anticoagulant proteins that degrade specific clotting factors , preventing excessive thrombosis following the initial clotting cascade.

Question 30

Outline all the primary secretions of the endothelial cells.

What do they express?

Answer 30

1.Prostacyclin and Nitric oxide, which prevent platelet aggregation by causing relation of smooth muscles.

2.CD39, ADPase: Inhibits platelet aggregation by cleavage of ADP back to AMP.

Question 31

State the 4 secretions of endothelial cells in secondary hemostasis.

Outline all the 3 endothelial cells expressions.

Answer 31

1.Protein S : cofactor of protein C and inactivates Factor Va and factor VIIIa

2.TPFI (tissue factor pathway inhibitor): Inactivate Factor X and XII

3.Tissue plasminogen activator: Activates plasminogen into plasmin.

4.ATIII (Anti-thrombin III):
- Cofactor of heparin
-Inhibits factor IIa and Xa
*Endothelial ProteinC receptor (EPCR): Clusters protein C in site of intact endothelial cells

*Thrombomodulin: Cofactor thrombin, together they cleave and activate protein C.

*GAG(Glucosummoglycans): Cofactor for ATIII, inactivate Factor II and Xa

.

Question 32

Outline all the activators of platelets.

Answer 32

1.Collagen
2.ADP
3.Thromboxane
4.Thrombin
5.Adrenaline

Question 33

What is the role of the liver in hemostasis?

Answer 33

It generates bile salts which are used in the absorption of Vitamin K (fat soluble vitamin).

It uses the Vitamin K to synthesize the clotting factors: Factor X,IX,VII,II

Question 34

State the 2 main receptors on platelets and their molecules.

Answer 34

gp-Ia-IIa: collagem

gp-IIb-IIIa:Fibrinogen

gp-Ib-IX-V:von Willebrand factor

Question 35

State the 3 main classes of drugs affecting hemostasis.

Answer 35

*Anti-platelets/ anti-aggregants
*Anti-coagulants
*Thrombolytics-

Question 36

State the different anti-aggregants/ anti-platelets

Answer 36

*Irreversible inhibitors of platelet cyclooxygenase.
MOA: Results in low Thromboxane A2

*Inhibitors of phosphodiesterase

*Inhibitors of receptors for ADP.

*Inhibitors of gp-IIb-IIIa

Question 37

Describe the MOA of the following anti-coagulants.
1.Heparin
2.Synthetic Pentasaccharides
3.Hirudins
4.Warfarin
5.Thrombolytic therapy
6.Thromboelectomy

Answer 37

*Cofactor of ATIII, indirect inhibitor of thrombin
*Inhibit factor IIa, Xa

Has 2 types;
*Un fractioned with half-life of 1Hr and the Low molecular wight heparins with a half-life of 5 hrs.

2.Direct inhibitors of Thrombin, half life 17hrs

3.Direct inhibitors of thrombin

4.Vitamin k antagonist

5.Dissolve arterial clots
*Direct; Streptokinase
*Indirect; Plasmionogen activator

6.Thromboembolectomy
*A Surgical removal of thrombus