Haemostasis and thrombosis

Question 1

What percentage of blood volume is made up by red blood cells?

Answer 1

45%

Question 2

Where are clotting factors found?

Answer 2

All within the plasma

Question 3

What is the difference between haemostasis and thrombosis?

Answer 3

Haemostasis- physiological process that prevents excessive blood loss
Thrombosis- Pathophysiological- a blood clot is forming but this doesn’t always involve the rupture of the blood vessel itself

Question 4

What is thrombosis normally only caused by?

Answer 4

Damage to the tunica intimate- it’s not stopping blood from leaking out because there is no hole in the first place so it’s pathophysiological

Question 5

What are red thrombi?

Answer 5

Venous clots because they contain lots of erythrocytes and thrombin

Question 6

What are white thrombi?

Answer 6

Arterial clots- they have a higher platelet component and are white because of macrophages entering the lesion and becoming foam cells

Question 7

What is virchow’s triad which offers explanations for increased probability of thrombus formation?

Answer 7

Rate of blood flow
Consistency of blood
Vessel wall integrity

Question 8

Why does rate of blood flow affect risk of thrombus formation?

Answer 8

Slow blood flow increases likelihood of thrombosis

Question 9

What is slow blood flow a common explanation for?

Answer 9

DVT in legs because BP is very low

Question 10

What affects the consistency of blood?

Answer 10

Balance between procoagulants and anticoagulants

Question 11

What are the three main stages of coagulation?

Answer 11

Initiation
Amplification
Propagation

Question 12

What types of drugs target each stage of coagulation?

Answer 12

Initiation- anticoagulants
Amplification- antiplatelets
Propagation- thrombolytics

Question 13

Initiation starts with a tissue factor bearing cell, what is on a tissue factor bearing cell?

Answer 13

Tissue factor and prothrombinase complex

Question 14

What does the prothrombinase complex consist of?

Answer 14

Factor 5a and factor 10a

Question 15

What does the prothrombinase complex do?

Answer 15

Converts prothrombin (zymogen) to thrombin (active enzyme)

Question 16

Where is antithrombin (AT-III) found and what does it do?

Answer 16

It is present within the blood and it inactivates factors 2a and 10a

Question 17

In terms of thrombin generation and breakdown, what happens normally?

Answer 17

Thrombin will be formed by prothrombinase complex and broken down by anti-thrombin

Question 18

Under pathological conditions, what can happen to thrombin?

Answer 18

Too much thrombin being formed

Question 19

What is dabigatran?

Answer 19

Factor 2a inhibitor- direct thrombin inhibitor and first oral anticoagulant

Question 20

What is the problem with dabigatran?

Answer 20

It can cause more bleeding than anticipated

Question 21

What is rivaroxaban?

Answer 21

Factor 10a inhibitor

Direct inhibitor of factor 10a- also taken orally

Question 22

What are dabigatran and rivaroxaban classified as?

Answer 22

Novel oral anticoagulant (NOAC)

Question 23

What does heparin do?

Answer 23

Increases activity of antithrombin (AT-III)

Very effective anticoagulant that can be given IV or SC

Question 24

What is different about low MW heparin than normal?

Answer 24

It has a longer half life and it activates the portion of antithrombin that is more concerned with breakdown of 10a more so than 2a

Question 25

What is an example of low MW heparin?

Answer 25

Dalteparin

Question 26

What does warfarin do?

Answer 26

Vitamin K antagonist- orally active

Question 27

What is vitamin K important for?

Answer 27

Gamma-carboxylation of factor 2,7,9 and 10 which is important for these to function

Question 28

When are anticoagulants mainly used?

Answer 28

Treat venous thromboses During surgery In atrial fibrillation to prevent stroke

Question 29

What does thrombin do to platelets?

Answer 29

It interacts with platelets and causes platelet activation

Question 30

What happens to a platelet when it becomes activated?

Answer 30

The platelet changes shape and becomes more sticky and they aggregate around the area of thrombus formation

Question 31

What sort of receptors are found on the surface of a platelet?

Answer 31

G protein coupled receptors called protease activated receptors (PAR)

Question 32

How does thrombin activate platelets?

Answer 32

It binds to PAR

Question 33

What happens once thrombin binds to PAR?

Answer 33

It causes an increase in intracellular calcium which causes a change in shape of the platelets and also causes exocytosis of ADP

Question 34

What does ADP do after being exocytosed by a platelet?

Answer 34

It either has an autocrine effect on same platelet or a paracrine effect on neighbouring platelets by binding to P2Y12 receptors (ADP receptors)

Question 35

What does ADP binding to the ADP receptor cause?

Answer 35

Platelet to become more sticky and more activated which also causes the liberation of arachidonic acid

Question 36

What happens to arachidonic acid once it is liberated?

Answer 36

It is acted upon by COX to convert it to prostaglandins and thromboxane A2

Question 37

What does thromboxane A2 do?

Answer 37

It increases the expression of GlpIIb/IIIa on the surface of the platelet- this makes the platelet sticky

Question 38

What is clopidogrel?

Answer 38

Oral P2Y12 receptor antagonist- prevents platelet activation/aggregation

Question 39

What is aspirin?

Answer 39

Irreversible COX-1 inhibitor- reduces the production of thromboxane A2

Question 40

What is abciximab?

Answer 40

Monoclonal antibody that is directed against GlpIIb/IIIa

Question 41

Why is abciximab not used that often?

Answer 41

Aspirin and clopidogrel are very effective

Question 42

When are antiplatelets commonly used?

Answer 42

Arterial thrombosis Acute coronary syndromes- clots in coronary arteries Atrial fibrillation

Question 43

What is there large scale production of on the surface of platelets?

Answer 43

Thrombin

Question 44

What does thrombin do apart from activating platelets?

Answer 44

Converts fibrinogen to fibrin

Question 45

What does fibrin do?

Answer 45

It traps all the platelets within it like a net

Question 46

What are thrombolytics also known as?

Answer 46

Clot busters

Question 47

How do thrombolytics work?

Answer 47

They activate plasmin (anticoagulant factor) which breaks down preformed clots

Question 48

What is an example of thrombolytic drug?

Answer 48

Alteplase (IV)- A recombinant tissue type plasminogen activator (tPa)

Question 49

What is the problem with thrombolytics?

Answer 49

They are a little too effective and cause a lot of bleeding- only used in life threatening and dangerous conditions within a certain time period

Question 50

What are thrombolytics used for?

Answer 50

First line treatment of stroke | STEMI

Question 51

Where are you most likely to get venous thromboses?

Answer 51

In the popliteal veins where there is stasis

Question 52

How do you prevent DVT?

Answer 52

Restore the balance and increase amount of anticoagulants: Prophylactically- anticoagulant drugs After a PE- heparin or low MW heparin

Question 53

What is the difference between NSTEMI and STEMI?

Answer 53

NSTEMI- Non-ST elevated myocardial infarction STEMI- ST elevated myocardial infarction STEMI is more dangerous

Question 54

What causes NSTEMI?

Answer 54

Partial occlusion of a coronary artery- can lead to stable angina

Question 55

What is used to treat NSTEMI?

Answer 55

Antiplatelets

Question 56

What causes STEMI?

Answer 56

Full occlusion of a coronary artery- causes unstable angina

Question 57

What is used to treat STEMI?

Answer 57

Anti platelet drugs but in severe cases you may use thrombolytics to dissolve the clot before there is too much damage to the heart muscle