Primary and Secondary Haemostasis

Question 1

Define Haemostasis?

Answer 1

Mechanism that leads to cessation of bleeding from a blood vessel

Question 2

What is the role of Primary Haemostasis?

Answer 2

Formation of platelet plug to fill small vascular holes

Question 3

What is the physiological mechanism that initiates haemostasis?

Answer 3

Vasoconstriction, as this limits blood flow to the injured region to reduce blood loss

Question 4

What is the name of the outside and inside layers of a blood vessel wall, and why are they important for haematostasis?

Answer 4

Outside of blood vessel is covered by subendothelium, which is composed of connective tissue and collagen to withstand high pressure, and can activate coagulation

Inside of the blood vessel is lined by endothelium which is a non-stick surface that is inert, so will not activate coagulation

Question 5

How does an injury affect vascular walls in a way that triggers haematostasis?

Answer 5

Injury damages endothelium and so subendothelium becomes exposed to circulating blood

Exposure triggers primary haemostasis

Question 6

In primary haemostasis, how is blood converted from its non-coagulant to coagulant form?

Answer 6

Exposure to collagen and connective tissue in subendothelium activates blood coagulant form

Question 7

In primary haemostasis, how do activated platelets maintain vasoconstriction of the injured vessel?

Answer 7

Secrete chemicals to maintain vasoconstriction

eg. Thromboxane (A2), serotonin (5HT), ADP

Question 8

In primary haemostasis, give 3 examples of chemicals that platelets secrete to maintain vasoconstriction?

Answer 8

Thromboxane (A2)

Serotonin (5HT)

ADP

Question 9

How can the mechanism of action of anticoagulant drugs relate to the chemicals released by platelets in primary haemostasis?

Answer 9

Anticoagulant drugs target these chemicals

eg. Aspirin targets thromboxane, clopidogrel targets ADP

Question 10

In primary haemostasis, what clotting factor activates platelets to begin to form a platelet mass?

Answer 10

Von Willebrand clotting factor

Question 11

In primary haemostasis, how does von Willebrand factor allow platelets to bind to the exposed subendothelium and damaged vascular area?

Answer 11

Von Willebrand clotting factor becomes bound to exposed collagen, so that platelet surface receptors can bind to von Willebrand factors

Question 12

In primary haemostasis, how does von Willebrand factor promote platelet aggregation in 2 main ways?

Answer 12

Platelet-von Willebrand binding stimulates platelets to change from inactive discoid shape to activated shape with higher SA:V ratio which promotes aggregation to other platelets and other von Willebrand clotting factors.

Adhesive interactions cause these other clotting factors and platelets to be recruited to the site of injury

Question 13

In primary haemostasis, describe the shape change of platelets and why this is important?

Answer 13

From inactive discoid shape to activated shape protrusions

Has higher SA:V ratio which promotes aggregation to other platelets and other von Willebrand clotting factors

Question 14

In primary haemostasis, how long does platelet aggregation go on for?

Answer 14

Aggregation occurs until injury in blood vessel is completely filled

Question 15

What is the role of secondary haematostasis?

Answer 15

Formation of fibrin through the coagulation cascade, to stabilise the platelet plug by forming a localised fibrin clot

Question 16

In secondary haemostasis, why is fibrin needed to stabilise the platelet plug?

Answer 16

Platelet plug isn’t stable enough to keep wound covered as it heals

Question 17

In secondary haemostasis, why is it important for fibrin generation to be localised to site of injured blood vessels?

Answer 17

So that clot doesn’t form elsewhere in body and can cause complications like stroke

Question 18

In secondary haemostasis, where do the clotting cascades for fibrin generation occur?

Answer 18

Phospholipid surface of platelets

Question 19

In secondary haemostasis, what are the 2 types of clotting cascades for fibrin clot formation, and when does each occur?

Answer 19

Intrinsic coagulation cascade responds to spontaneous internal damage of vascular endothelium, through clotting factors that circulate in blood vessels

Extrinsic coagulation cascade responds secondary to external trauma, through tissue factor which comes from outside of blood vessels

Question 20

In secondary haemostasis, explain the steps of the intrinsic clotting cascade until the common pathway?

Answer 20

1. Factor 12 is activated to become 12a (a denotes activated form)
2. 12a amplifies activation of factor 11 to 11a
3. 11a amplifies activation of factor 9 to 9a
4. 9a amplifies activation of factor 8 to 8a
5. 9a and 8a together activate factor 10 to 10a, now becomes common pathway

Question 21

In secondary haemostasis, explain the steps of the extrinsic clotting cascade until the common pathway?

Answer 21

1. Tissue factor is released from injured tissues into circulation, where it binds with factor 7 to amplify activation in 7a
2. 7a amplifies activation of factor 10 to 10a, now becomes common pathway

Question 22

In secondary haemostasis, explain the steps of the common pathway?

Answer 22

1. Factor 10 converted to 10a
2. 10a converts prothrombin (factor 2) into thrombin (factor 2a)
3. Thrombin converts fibrinogen (factor 1) into fibrin

Question 23

Define fibrolysis?

Answer 23

Clot dissolution so that it can be broken down and removed

Question 24

In haemostasis, explain how fibrolysis occurs?

Answer 24

Plasminogen produces plasmin, which breaks down the fibrin into Fibrin Degradation Products (FDPs)/D-dimers