Lecture 6: Haemostasis (PART OF HAEMATOLOGY)

Question 1

How many systems are involved in haemostasis?

Answer 1

5.

Question 2

What are the names of the systems involved in haemostasis?

Answer 2

• The vascular system
• Platelets
• Coagulation cascade
• Inhibitors of coagulation
• Fibrinolytic system

Question 3

What is homestasis?

Answer 3

A sub-branch of homeostasis concerning blood.
It is an important mechanism to minimize blood following injury, while keeping blood from clotting in vasculature.
Haemostasis is a complex interaction of 5 distinct systems.

Question 4

What role does the vascular system play in haemostasis?

Answer 4

Vasoconstriction plays an essential role in haemostasis, modulated by adrenaline, ADP and thromboxanes, which are released by thrombocytes.
The vascular endothelial cells are a source of pro and anti-thrombotic compounds, which leads to formation of blood clots.

Question 5

What role do thrombocytes perform in haemostasis?

Answer 5

These cells, formed by a progenitor cell called a megakaryocyte. Reference range for thrombocytes is 150-400x10^9 cells/l
Platelet granules, held in the cytosol of thrombocytes, play an important role in haemostasis: dense granules, alpha granules and lysosomes.

Question 6

What role do alpha granules play in a thrombocytes function?

Answer 6

Alpha granules, which number around 200 per cell, contain several regulators of haemostasis, these being fibrinogen (pro-coagulant), Factor V (pro-coagulant), and Von Willebrand Factor, which serves as an adhesion molecule.

Question 7

Dense granules perform what function in thrombocyte function?

Answer 7

Dense granules, numbering around 10 per cell also contain several key compounds including: calcium ions, ADP and serotonin, which is a potent vasoconstrictor.

Question 8

What is the primary role of platelets?

Answer 8

The formation of a platelet plug, or a large group of thrombocytes, which acts as a temporary barrier to prevent blood loss (primary haemostasis).

Question 9

What are the 4 phases of primary haemostasis?

Answer 9

• Platelet adhesion
• Platelet shape change
• Release of platelet granules
• Platelet aggregation

Question 10

What is platelet adhesion?
(primary haemostasis)

Answer 10

Once thrombocytes are activated through contact with any number of physiological substances (collagen, charged surface, bacterial endotoxin, etc). These activator compounds will not normally be present until injury. (eg. charged sections of basement membrane being exposed after endothelial damage).

Question 11

What is platelet shape change (primary haemostasis)

Answer 11

Once bound to substrate, platelets become activated and change their shape as in the prevent gaps from being present (which there would be given they remain spherical. The new ‘dendritic’ shapes will fit together more closely, filling in gaps and preventing any diapedesis or fluid leakage.

Question 12

What is the release of platelet granules?
(primary haemostasis)

Answer 12

After thrombocytes have bound and changed shape to tightly pack together,

Question 13

What is platelet aggregation?
(primary haemostasis)

Question 14

What is secondary haemostasis?

Question 15

What are coagulation factors?

Answer 15

A collection of substates, enzymes and cofactors that are responsible for the functions of thrombocytes and blood clotting.

Question 16

What are the four classes of coagulation factor?

Answer 16

• Substrate
• Serine protease
• Cofactor
• Transglutaminase

Question 17

What are serine proteases?

Answer 17

Enzymes that employ the use of a serine as a catalytic site amino acid.
This enzyme is prevalent in almost all vascular systems in the animal kingdom. The age of this enzyme speaks to its efficacy as a coagulation factor.

Question 18

What role does vitamin K (quinone) play in blood coagulation?

Answer 18

Vitamin K is involved in the activation via carboxylation of several pro- and anti-coagulants. These activated factors bind calcium ions, which are hugely important in clotting.

Question 19

How does Warfarin function as an anticoagulant?

Answer 19

A drug commonly used for the treatment of thrombo-embolic disease.
Warfarin inhibits Vitamin K- carboxylase epoxidase.
Also used as a rat poison.

Question 20

How was warfarin discovered?

Answer 20

Due to a fungus that

Question 21

What is the blood coagulation cascade?

Question 22

What is the extrinsic pathway of the In Vitro model of the coagulation cascade?

Answer 22

Tissue factor, which is expressed on damaged endothelial cells will form a complex with both active and inactive FVII.
TF:FVIIa complex then activates FX and FXa and enters the common pathway.

Question 23

((((((Relationship between factor X and warfarin here)))))

Question 24

What is prothrombin time and how does it relate to the extrinsic pathway of in vitro coagulation cascade?

Question 25

What is the intrinsic pathway of the In Vitro model?

Answer 25

Initiated by contact with a negatively charged surface. This negative charge initiates activation of FXII

Question 26

What is the common pathway of the In Vitro model of the coagulation cascade?

Answer 26

The common pathway leads to the conversion of soluble fibrinogen into insoluble fibrin.
FXIIIa stabilises the fibrin mesh by producing cross-links.

Question 27

What is the initiation phase of the In Vivo model of the coagulation cascade?

Question 28

What is the Amplification phase of the In Vivo model of the coagulation cascade?

Question 29

What is the propagation phase of the In Vivo model of the coagulation cascade?

Question 30

What is fibrinogen?

Answer 30

One of the most plentiful plasma proteins in our blood. It is produced by hepatocytes (~3g/L on average).
It is a symmetrical hexamer (symmetrical pair of 3 chains).
It is cleaved by thrombin into fibrinogen.

Question 31

How is the regulation of secondary haemostasis controlled?

Question 32

What is antithrombin (III)?

Question 33

What is Heparin?

Question 34

What is protein C?

Question 35

What is protein S?

Question 36

What is the role of fibrinolysis?