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 foam cells (macrophages that have taken up lipids). Associated with atherosclerosis

Question 4

What are the three parts of Virchow’s triad?

Answer 4

1) Rate of blood flow
Blood flow is slow/stagnating = no replenishment of anticoagulant factors & balance adjusted in favour of coagulation

2) Consistency of blood
Natural imbalance between procoagulation & anticoagulation factors

3) Blood vessel wall integrity
Damaged endothelia = blood exposed to procoagulation factors

Question 5

What does the tissue factor-bearing cell contain?

Answer 5

Tissue Factor

Prothrombinase Complex = Factor 5a + Factor 10a

Question 6

Describe the process of initiation.

Answer 6

TF bearing cells activate factor V and factor X forming the prothrombinase complex (Va + Xa)
The prothrombinase complex converts fII -> IIa (prothrombin to thrombin)

Question 7

What is responsible for the inactivation of factors IIa and Xa?

Answer 7

Antithrombin (AT-III)

Question 8

State some drugs that target the initiation stage of coagulation, how they work and how they’re administered.

Answer 8

1) Inhibit factor IIa:
Dabigatran (oral)

2) Inhibit factor Xa:
Rivaroxaban (oral)

3) Increase activity of AT-III:
Heparin (IV, SC)

Low-molecular weight heparins (LMWHs) e.g. Dalteparin (parenteral) - preferentially tragets fXa

4) Inhibits the production of factors II, VII, IX and X:
Warfarin (oral)
Vitamin K epoxide reductase inhibitor

Question 9

What are the indications of these anti-coagulants?

Answer 9

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

Question 10

Describe the amplification stage of coagulation.

Answer 10

Thrombin (fIIa) activates platelets and makes them change to a stellate shape and become more sticky so that they aggregate

Question 11

Explain, in detail, how thrombin causes platelet activation.

Answer 11

Thrombin (fIIa) - binds to protease-activated receptor (PAR) on platelet surface.
PAR activation -> rise in intracellular Ca2+
Ca2+ rise -> exocytosis of adenosine diphosphate (ADP) 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

PAR activation -> liberates arachidonic acid (AA)

Cyclo-oxygenase (COX) generates thromboxane A2 (TXA2) from AA

TXA2 activation -> expression of GPIIb/IIIa integrin receptor on platelet surface
GPIIb/IIIa - involved in platelet aggregation

Question 12

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

Answer 12

Aspirin (oral) – irreversible COX1 inhibitor – it reduces the production of thromboxane by platelets

Clopidogrel (oral) – irreversible ADP (P2Y12) receptor antagonist

Abciximab (IV,SC) – monoclonal antibodies directed at GlpIIb/IIIa

Question 13

What are the indications of these anti-platelet drugs?

Answer 13

Arterial thrombosis:
Acute coronary syndromes – myocardial infarction

Atrial fibrillation – prophylaxis of stroke

Question 14

Describe the propagation stage of coagulation.

Answer 14

Thrombin converts fibrinogen to fibrin so fibrin strands are generated

Question 15

Name an important thrombolytic and explain how it acts.

Answer 15

Alteplase – it is a recombinant tissue plasminogen activator (tPA)

Plasminogen is converted to plasmin, which is a protease that degrades fibrin

Question 16

What are the indications of thrombolytics?

Answer 16

First line treatment for stroke

STEMI

Question 17

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

Answer 17

Popliteal veins

Question 18

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

Answer 18

Prophylactically – anticoagulants

After it happens – heparin or low MW heparin

Question 19

What is an acute coronary syndrome?

Answer 19

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

Question 20

What is NSTEMI?

Answer 20

Non-ST elevation myocardial infarction

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

Question 21

Describe the management of NSTEMI.

Answer 21

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

Question 22

What is STEMI?

Answer 22

ST-elevation myocardial infarction

This is caused by FULL occlusion of a coronary artery

Question 23

Describe the management of STEMI.

Answer 23

Anti-platelet drugs

Sometimes thrombolytics if the clot needs to be dissolved

Question 24

Why is Dabigatran no longer used?

Answer 24

It has a dangerous GI side effect profile.

Question 25

What does the D-dimer test look for?

Answer 25

Fibrin degradation products

Question 26

Whats the difference in pharmacological managemnt of DVT and a PE?

Answer 26

PE is more serious
DVT management = Dalteparin interim treatment then rivaroxiban and warfarin

PE management = Dalteparin and heparin interim then rivaroxaban and warfarin