Haemostasis

Question 1

What is meant by haemostasis?

Answer 1

This a physiological response aimed to stop the loss of blood this is done by causing the arrest of bleeding caused due to vasoconstriction, platelet aggregation and blood coagulation.

Question 2

What effects does the vascular wall collagen have on platelets?

Answer 2

This causes the platelets to swell altering shape, become adhesive and degranulate.

Question 3

What does the degranulation of platelets releases and what do the molecules released cause?

Answer 3

5-HT causes a vascular spasm
Thromboxane A2 causes platelet activation
ADP causes platelet aggregation.

Question 4

What causes loose aggregation of platelets to become bound together into a clot?

Answer 4

Fibrin causes the binding of loose aggregations into a clot.

Question 5

What are the key steps involved in the formation of fibrin?

Answer 5

Fibrin is formed from the conversion of soluble fibrinogen to insoluble fibrinogen monomers and these are polymerised into fibrin.

Question 6

What causes venous thromboembolism to occur?

Answer 6

Venous thromboembolism occurs as a result of slow blood flow allowing the clotting factors to accumulate.

Question 7

What factors are associated with venous thromboembolism?

Answer 7

Immobility, dehydration and hormonal changes.

Question 8

What are the two types of venous thromboembolism?

Answer 8

Deep vein thrombosis in the leg.

Pulmonary embolism.

Question 9

What type of treatment is given to patients with VTE?

Answer 9

Anticoagulants need to be given.

Question 10

Name the two types of anticoagulants used in patients with VTE.

Answer 10

Heparins

Warfarin ( Vitamin K antagonist)

Question 11

What is the overall action achieved through the use of anticoagulants?

Answer 11

They reduced the ability of the blood to coagulate prolonging clotting times.

Question 12

What are the two types of herapins?

Answer 12

Unfractionated and Low molecular weight herapins.

Question 13

How do herapins work as a anticoagulant?

Answer 13

Herapins bind to antithrombin III usually forms complexes with thrombin to inactivate it, binding to herapin increases the rate of complex formations inactivating thrombin.

Question 14

The other anticoagulant used is warfarin. What is the mechanism of action of warfarin and how does this affect clotting?

Answer 14

Warfarin is a competitive vitamin K reductase inhibitor an essential enzyme for activating vitamin K in the body which is used to produce clotting factors II, VII, IX and X so inhibition caused no formation of complexes
Warfarin is only active in vivo.

Question 15

What is the INR and what is it used to check?

Answer 15

INR is a international normalised ratio and is a blood test to check how long it takes for the blood to clot using prothrombin time.

Question 16

What effect does warfarin have on INR, what is the value for a ‘normal’ INR and what does it mean to have a INR higher then normal?

Answer 16

Warfarin increases INR and a normal INR is 0.9 to 1.2 and the higher the INR the longer the blood takes to clot.

Question 17

What are the different warfarin tablet strengths and what colour are these?

Answer 17

0.5mg - White
1mg - Brown
3mg - Blue
5mg - Pink

Question 18

What is the maintenance dose of warfarin and how does dosing differ in patients?

Answer 18

The maintenance dose for warfarin is 3mg to 9mg and differs dependent on how far they are from target INR.

Question 19

Give some examples of other anticoagulant drugs. (5 examples)

Answer 19

Lepriduin
Dabigatran
Rivaroxaban
Axpiaban
EDTA

Question 20

What are the advantages involved with the use of anticoagulants such as rivaroxaban compared to warfarin?

Answer 20

They have no dose variation, no INR monitoring and no food interactions and fewer interactions.

Question 21

Which thrombosis is antiplatelet drugs most effective in?

Answer 21

They are most effective in arterial thrombosis.

Question 22

What mechanism of action allows aspirin to be useful in the limiting and prevention of thrombosis?

Answer 22

Aspirin inhibits COX by acetylation, stopping platelets from producing thromoboxane A2 so phospholipase C is not stimulated and inositol trisphosphate is not produced, so calcium ion levels do not rise and platelets remain dormant.

Question 23

What COX is possessed by platelets and what is the only way for platelet function to return following irreversible inhibition?

Answer 23

COX-1 is the only one possessed and once inhibited function only return by the production of new platelets which takes 7-10 days.

Question 24

Where are GPllb/llla receptors found and what affinity for fibrinogen do these receptors possess?

Answer 24

These receptors are found on platelet membranes and they have a high affinity to fibrinogen.

Question 25

What are abciximab, tirofiban and eptifibatide examples of?

Answer 25

These are examples of GPllb/llla inhibitors.

Question 26

What does the inhibition of GPllb/llla receptor cause?

Answer 26

Inhibition of the GPllb/llla receptor means that cross links between cannot form as fibrinogen cannot bind to the receptor this prevents platelet aggregation.

Question 27

What are some other examples of antiplatelet drugs?

Answer 27

Clopidogrel, prasugrel, ticagrelor, dipyridamole, tirofiban.

Question 28

What is the action of fibrinolytic drugs in breaking down thrombi?

Answer 28

These cause the breakdown of thrombi by converting plasminogen into plasmin which is a enzyme to fibrin causing the breakdown and restoration of the vessel.

Question 29

What is an example of a enzymatic protein used as a thrombolytic drug?

Answer 29

Streptokinase is a enzymatic protein extracted from streptococcal bacteria.

Question 30

What is used instead of streptokinase to activate plasminogen?

Answer 30

Tissue-type plasminogen activators such as alteplase.