L5. Haemostasis

Question 1

What interactions are involved in haemostasis?

Answer 1

The interaction between platelets, coagulation factors and inhibitors, fibrinolysis and the blood vessels, endothelium, cellular membranes of cells

Question 2

What is the haemostatic profile of the normal endothelium?

Answer 2

Normally the endothelium is an anti-coagulative barrier actively releasing factors that prevent coagulation from occurring.

Question 3

What happens when there is a break or dysfunction to the endothelial lining?

Answer 3

Exposure of the subendothelium leaves pro-cogaulative and pro-thrombotic factors exposed and they interact with the blood and blood cells leading to:
platelet accumulation
primary plug
fibrin mesh formation over the top
fibrinolytic pathways

Question 4

What are the main processes involved in primary haemostasis and the time frame at which they occur?

Answer 4

1. Vasoconstriction: immediately
2. Platelet adhesion: seconds
3. Platelet aggergation: minutes

Question 5

What are the main processes involved in secondary haemostasis and the time frame at which they occur?

Answer 5

1. Activation of coagulation factors in the plasma: minutes

2. Formation of fibrin: Also minutes

Question 6

What is involved in fibrinolysis?

Answer 6

1. Activation of fibrinolytic pathways (minutes)

2. Lysis of the clot (hours)

Question 7

What is Virchov’s Triad?

Answer 7

Describes the predisposing features that lead to thrombosis:
1. Abnormal endothelium
2. Abnormal flow
3. Abnormal blood components
Any one of these factors leads to thrombosis

Question 8

What features of the endothelial wall can affect coaguability?

Answer 8

• Expression of surface molecules
• Interaction with cell surface proteins
• Vascular smooth muscle tone: Arterial or Vein
• The endothelium changes with age (decreases compliance)

Question 9

Describe the coagulation system

Answer 9

A complex series of protein pathways in the plasma that interact with platelets and vessel walls.

Question 10

What is the major starter for the extrinsic pathway of the coagulation cascade?

Answer 10

TF is produced by endothelial cells and secreted into the smooth muscle layers. Exposure of the smooth muscle layers exposes TF and this starts the extrinsic pathway of coagulation.

Question 11

What is meant by there is a redundancy in the coagulation system? Give examples

Answer 11

Some factors of the coagulation system have overlapping functions.
Eg. Absence of Factor XII leads to no problems to the system while an complete absence of factor XIII leads to haemophilia (partial absence is asymptomatic)

Question 12

What is the major controlling enzyme of the coagulation cascade?

Answer 12

THROMBIN
An enzyme that controls and decides the feedback loops.
It cleaves fibrinogen to fibrin
It is the common pathway (convergence of extrinsic and intrinsic)

Question 13

What processes is the coagulation cascade involved in?

Answer 13

Wound repair, inflammation, angiogenesis and other regulatory systems

Question 14

Draw the pathway:

Answer 14

Extrinsic: TF –> XII –> XI –> IX –> X: PT into T which leads Fibrinogen into Fibrin
Intrinsic: VII –> X

Question 15

What are the three phases of clot formation?

Answer 15

1. Initiation Phase
2. Amplification Phase
3. Propagation Phase

Question 16

Describe the initiation phase of clot formation

Answer 16

Vessel injury exposes TF which activates XII setting off a cascade that leads to the eventual activation of X. Active X (Xa) binds to activated Va (present on the surface of endothelial cells).

Question 17

Describe the amplification phase of clot formation

Answer 17

Run by positive feedback mechanisms
The Xa:Va complex activates some thrombin from prothrombin.
Thrombin activates more factors to amplify the process while also activating platelets (which in turn activates more factors)

Question 18

Describe the propagation phase of clot formation

Answer 18

Extension of the clot outwards to form the stable fibrin clot
The activated platelets plus activation phase results lead to a THROMBIN BURST recruiting and aggregating more platelets.

Question 19

What do levels of thrombin mean for haemostasis?

Answer 19

Insufficient thrombin = bleeding while too much = thrombosis (clotting)

Question 20

Describe the three major global tests for bleeding

Answer 20

ACT: activating clotting time
APTT: Activated partial thromboplastin time: (intrinsic + common pathway) and measures the time taken to form fibrin
PT: Prothrombin Time (also measured by the INR): for the extrinsic pathway: major monitor for warfarrin