Clotting Cascade

Question 1

What are the stages of haemostasis?

Answer 1

1) Vascular phase
2) Platelet phase
3) Coagulation phase

Question 2

What are the components of the first stage of haemostasis?

Answer 2

Vascular phase: damage to call causes vasoconstriction. Damage to endothelial cells causes release of factors and expression of surface factors to make them “sticky”.

Question 3

What is released by endothelial cells during the vascular phase of haemostasis?

Answer 3

• ADP
• Tissue factor (factor III)
• Prostacyclin (-ve feedback, causes vasodilation, inhibits platelet plug formation)
• Endothelins: hormones.

Question 4

What are endothelins?

Answer 4

Primary hormones in vascular phase of haemostasis. Stimulate smooth muscle contraction, division of endothelial cells, smooth muscle cells and fibroblasts (repair damaged site).

Question 5

What occurs when a platelet becomes attached to a damaged endothelial surface?

Answer 5

• Swelling: becomes large and irregular

- Contraction of contractile proteins: granule release (ADP, thromboxane and Ca2+ ions ==> attract nearby platelets.)

Question 6

What is contained in platelet granules?

Answer 6

Two types: alpha and dense

• Alpha: growth factors e.g. fibrinogen and PDGF
• Dense: non-proteins (thromboxane, serotonin adrenaline, histamine, calcium, ATP and ADP).

Question 7

Negative feedback regulation of platelet plug formation?

Answer 7

• Prostacyclin (from endothelium)
• WBCs release inhibitory proteins
• Plasma enzymes: degrade ATP

Question 8

What is the clotting cascade?

Answer 8

Two separate pathways (intrinsic and extrinsic) –> join to form common pathway.
Begins ~30s after initial.
Ultimately causes activation of fibrin to fibrinogen.

Question 9

What initiates the intrinsic clotting pathway?

Answer 9

Exposure of blood to collagen (or other damaged surface) leading to formation of factor V.

Question 10

What activates the extrinsic clotting pathway?

Answer 10

Damaged endothelial cells release factor III (tissue factor).
Leads to formation of VIIa-tissue factor complex.

Question 11

What is the common pathway?

Answer 11

X activated (by VIIa or Va) to form  Xa (aka prothrombinase). Prothrombin --> Thrombin.
Fibrinogen --> fibrin.

Question 12

How is the clotting cascade regulated?

Answer 12

• TFPI: tissue factor pathway inhibitor. Directly inhibits Xa.
• ATIII: circulating enzyme binds thrombin (imp for action of heparin).
• Activated fibrin: inactivates thrombin.