Haemostasis

Question 1

What are the 3 stages of the cell-based theory of coagulation?

Answer 1

1. Initiation
2. Amplification
3. Propagation

Question 2

Summarise the events of the initiation stage of coagulation

Answer 2

Small-scale production of thrombin on TF-bearing cells

Question 3

Describe the mechanism by which TF triggers thrombin production

Answer 3

TF-bearing cells activate Factors X and V
FX and FV trigger formation of the prothrombinase complex
Prothrombinase complex activates factor II –> IIa (prothrombin –> thrombin)

Question 4

What is the mechanism of action of antithrombin?

Answer 4

Inactivates thrombin (FIIa) and Factir Xa

Question 5

What class of drugs targets the initiation phase of coagulation?

Answer 5

Anti-coagulants

Question 6

Recall an example of a factor IIa inhibitor

Answer 6

Dabigatran

Question 7

Recall an example of a factor Xa inhibitor

Answer 7

Rivaroxaban

Question 8

Recall the mechanism of action of heparin

Answer 8

Activates antithrombin

Question 9

Recall an example of a low-molecular weight heparin

Answer 9

Dalteparin

Question 10

What is the mechanism of action of warfarin

Answer 10

Inhibits Vit K which is essential for generation of factors II, VII, IX and X

Question 11

What is the main indication for anti-coagulant use?

Answer 11

VENOUS thrombi

Question 12

Recall 3 examples of when anti-coagulant therapy may be used

Answer 12

DVT
Thrombosis during surgery
Stroke prevention in AF patients

Question 13

Summarise the events of the amplification stage of coagulation

Answer 13

Large-scale production of thrombin on platelets, overwhelming anti-thrombin to lead to platelet activation

Question 14

Recall the 2 ways in which PAR activation brings about platelet aggregation

Answer 14

1. PAR activation –> rise in IC CA++. Ca++ –> ADP exocytosis from dense granules. ADP auto-activates platelets via ADP receptor called P2Y12 –> platelet aggregation
2. PAR activation –> arachdionic acid production –> TXA2 generation –> GPIIb and GPIIIa expression –> platelet aggregation

Question 15

Describe the biochemical mechanism by which thrombin triggers platelet-aggregation pathways

Answer 15

Binds to Protease-Activated-Receptor (PAR) on platelets

Question 16

Give 3 examples of anti-platelet drugs

Answer 16

1. Clopidogrel
2. Aspirin
3. Abciximab

Question 17

Recall the mechanism of action of clopidogrel

Answer 17

ADP-receptor antagonist - prevents platelet activation + aggregation

Question 18

Recall the mechanism of action of aspirin

Answer 18

Irreversible COX1 inhibitor - inhibits TXA1 production

Question 19

Recall the mechanism of action of abciximab

Answer 19

Inhibits GPIIb/IIIa receptor –> inhibition of platelet aggregation

Question 20

What is the main indication for anti-platelet drugs?

Answer 20

ARTERIAL thromboses

Question 21

Differentiate the treatment strategies for NSTEMIs and STEMIs

Answer 21

NSTEMI: anti-platelet to reduce lipid accumulation + platelet aggregation
STEMI: need anti-platelet to reduce lipids and platelet aggregation as well as a thrombolytic to dissolve thrombus as it is bigger

Question 22

Summarise the events of the propagation phase of coagulation

Answer 22

Thrombin-mediated generation of fibrin strands from circulatory fibrinogen

Question 23

What is the normal physiological function of fibrin

Answer 23

Fibrin strands come together to form a net that holds clot together

Question 24

What sort of drugs are used to target the propagation phase of coagulation

Answer 24

Thrombolytics - these can reduce a pre-formed clot

Question 25

Within what time-frame are thrombolytics effective?

Answer 25

30 mins

Question 26

Recall the general mechanism of action of thrombolytics

Answer 26

Activate plasmin from plasminogen, plasmin-protease degraded fibrin

Question 27

Recall an example of a thrombolytuc drug

Answer 27

Alteplase = recombinant plasminogen activator

Question 28

Recall 2 possible occasions when thrombolytics might be used

Answer 28

First-line treatment for stroke

ST-elevated MI (STEMI)

Question 29

Recall 4 examples of pro-coagulant clotting factors in plasma

Answer 29

Prothrombin
Factor V
Factor VII
Fibrinogen

Question 30

Recall 4 examples of anti-coagulant clotting factors in plasma

Answer 30

Plasminogen
TFPI
Proteins C and S
Antithrombin

Question 31

Differentiate the composition and site of red and white thrombi

Answer 31

Red = high fibrin component, forms within veins
White = high platelet component, forms within atherosclerotic plaque

Question 32

What is the main risk associated with red thrombi?

Answer 32

Life-threatening emboli

Question 33

What is the main risk associated with white thrombi?

Answer 33

Plaque rupture to release thrombus into arterial lumen and cause ischaemia

Question 34

Recall the triad of factors that lead to thrombus production

Answer 34

1. Low rate of blood flow
2. Consistency of blood
3. Vessel wall integrity

Question 35

How does blood flow rate affect risk of thrombus production?

Answer 35

Anticoagulant factors are not replenished due to stagnant flow

Question 36

What does the term “consistency” refer to in the blood?

Answer 36

Balance of pro- and anti-coagulant factors (NOT viscosity)

Question 37

Give an example of a disorder that result in high consistency of blood

Answer 37

Factor V Leiden - it cannot be inactivated by the normal factor V-deactivating processes

Question 38

What drugs are used to combat thrombus production?

Answer 38

Anti-coagulants

Question 39

What are the 2 main CVD disease states associated with venous pathology?

Answer 39

DVT

PE

Question 40

What are the 2 main CVD disease states associated with arterial pathology?

Answer 40

Stroke
Acute coronary syndrome
Aortic aneurysm
AF