Haemostasis and Thrombosis

Question 1

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

Answer 1

Around 45%

Question 2

What normally has to be damaged for a thrombus to form?

Answer 2

Tunica intima

Question 3

What is the difference between red and white thrombi?

Answer 3

Red – forms in veins – rich in fibrin and red blood cells

White – forms in arteries – rich in platelets and macrophages (foam cells)

Question 4

What are the three parts of Virchow’s triad?

Answer 4

Stasis
Vessel wall injury
Hypercoagulability/consistency of blood (balance between procoagulants and anti-coagulants)

Question 5

What are the three stages in the cell based theory of coagulation? State which types of drugs target each of the different stages.

Answer 5

Initiation – small-scale production of thrombin – ANTI-COAGULANTS
Amplification – large-scale thrombin production on the surface of platelets – ANTI-PLATELETS
Propagation – thrombin mediated generation of fibrin strands - THROMBOLYTICS

Question 6

What does the tissue factor-bearing cell contain?

Answer 6

Tissue Factor

forms Prothrombinase Complex by acitvation of Factor 5a + Factor 10a

Question 7

Describe the process of initiation.

Answer 7

TF bearing cells activate factor 5 and factor 10 forming the prothrombinase complex (5a + 10a)
The prothrombinase complex converts prothrombin to thrombin

Question 8

What is responsible for the inactivation of factors 2a and 10a?

Answer 8

Antithrombin (AT-III)

Question 9

State some drugs that target the initiation stage of coagulation.

Answer 9

Dabigatran – factor 2a inhibitor (oral – NOAC)
Rivaroxaban – factor 10a inhibitor (oral – NOAC)
Heparin – potentiates antithrombin – less 2a + 10a (IV/SC)
Low Molecular Weight Heparin (e.g. Dalteparin) – activates antithrombin – preferentially targets factor 10a
Warfarin – vitamin K epoxide reductase inhibitor – inhibits the production of factors 2, 7, 9 and 10

Question 10

What are the indications of these anti-coagulants?

Answer 10

Venous thromboembolism (DVT + PE)
Prevent thrombosis during surgery
Atrial fibrillation – prophylaxis of stroke

Question 11

Describe the amplification stage of coagulation.

Answer 11

Thrombin activates platelets and makes them more sticky so that they aggregate

Question 12

Explain, in detail, how thrombin causes platelet activation.

Answer 12

Thrombin binds to PAR (platelet activated receptor) on the platelet membrane
This causes an increase in intracellular Ca2+ concentration
This stimulates ADP exocytosis from dense granules
The ADP then binds to P2Y12 receptors (ADP receptor) on the same platelet or on neighbouring platelets, which leads to platelet activation/aggregation
Thrombin binding to the PAR also liberates arachidonic acid The arachidonic acid is converted by COX to thromboxane A2
Thromboxane A2 increases expression of GlpIIb/IIIa (which is involved in platelet aggregation)

Question 13

State three drugs that target the amplification stage of coagulation and explain how they act.

Answer 13

Aspirin – irreversible COX1 inhibitor – it reduces the production of thromboxane by platelets
Clopidogrel – irreversible ADP (P2Y12) receptor antagonist
Abciximab – monoclonal antibodies directed at GlpIIb/IIIa

Question 14

What are the indications of these anti-platelet drugs?

Answer 14

Arterial thrombosis:  Acute coronary syndromes – myocardial infarction  Atrial fibrillation – prophylaxis of stroke

Question 15

Describe the propagation stage of coagulation.

Answer 15

Thrombin converts fibrinogen to fibrin so fibrin strands are generated

Question 16

Name an important thrombolytic and explain how it acts.

Answer 16

Alteplase – it is a recombinant tissue plasminogen activator (tPA)
Plasminogen is converted to plasmin, which is a protease that degrades fibrin

Question 17

What are the indications of thrombolytics?

Answer 17

First line treatment for stroke

STEMI

Question 18

What is a common site for the formation of deep vein thrombosis?

Answer 18

Popliteal veins

Question 19

How can DVT and PE be treated, either prophylactically and after it has happened?

Answer 19

Prophylactically – anticoagulants

After it happens – heparin or low MW heparin

Question 20

What is an acute coronary syndrome?

Answer 20

Any condition brought on by sudden, reduced blood flow to the heart

Question 21

What is NSTEMI?

Answer 21

Non-ST elevation myocardial infarction

This is caused by partial occlusion of a coronary artery and it can lead to stable angina

Question 22

Describe the management of NSTEMI.

Answer 22

Anti-platelets (e.g. clopidogrel and aspirin)

Question 23

What is STEMI?

Answer 23

ST-elevation myocardial infarction

This is caused by FULL occlusion of a coronary artery

Question 24

Describe the management of STEMI.

Answer 24

Anti-platelet drugs

Sometimes thrombolytics if the clot needs to be dissolved