Haemostasis and thrombosis

Question 1

Name some procoagulant factors

Answer 1

Prothrombin
Factors V, VII-XIII
Fibrinogen

Question 2

Name some anticoagulant factors

Answer 2

Plasminogen
TFPI (Tissue factor pathway inhibitor)
Proteins C & S
Antithrombin

Question 3

What is meant by a red thrombi?

Answer 3

Venous thromboses
High fibrin component
Clot could embolise
Treat using anticoagulants

Question 4

What is meant by a white thrombi?

Answer 4

Arterial thromboses (thrombus forms within atherosclerotic plaque)
High platelet content
Plaque dislodgement -> ischaemia
Treat using anti platelets

Question 5

What is virchow’s triad?

Answer 5

1. Rate of blood flow: blood flow is slow so there is no replenishment of anticoagulant factors
2. Consistency of blood flow: imbalance between anticoagulant and pro coagulation factors
3. Blood vessel wall integrity

Question 6

What do anticoagulants, anti platelets and thrombolytics target in the process of coagulation?

Answer 6

Anticoagulants: Initiation (small scale thrombin production)
Antiplatelets: Amplification
Propagation: thrombolytics

Question 7

Describe the process of initiation

Answer 7

1. Tissue factor cells produce Factor V and 10 (prothrombinase complex)
2. Prothrombinase complex activates Factor 2 (prothrombin) -> Factor 2a (thrombin)
3. Antithrombin (AT-III) inactivates Factor 10 and Factor 2a

Question 8

Which drug inhibits Factor IIa?

Answer 8

Dabigatran

Question 9

Which drug inhibits Factor I0a?

Answer 9

Rivoraxiban

Question 10

How does heparin work as an anticoagulant?

Answer 10

Activates AT-III (inhibits Factor 10a and 2a)

Low molecular weight heparin activates AT-III but also directly inactivates Factor 10a.

Question 11

How does warfarin work as an anticoagulant?

Answer 11

Vitamin K antagonist

Vitamin K is needed for making Factors 2, 7, 9 and 10

Question 12

In what cases would you use anticoagulants?

Answer 12

Venous thromboses:
Deep vein thrombosis and pulmonary embolism
Thrombosis during surgery
Atrial fibrillation-prophylaxis for stroke

Question 13

Describe the process of amplification

Answer 13

Factor 2a activates platelets

Platelet changes shape, becomes ‘sticky’ and leads to aggregation

Question 14

Describe the process of platelet activation

Answer 14

Thrombin binds to protease activated receptor (PAR) and stimulates increase in intracellular calcium -> release of ADP from dense granules.

1. ADP binds to P2Y[12] receptor involved in platelet activation/aggregation.
2. PAR also stimulates COX production from arachidonic acid -> generates Thromboxane A2
3. Thromboxane A2 stimulates expression of GpIIb/IIIa integrin receptor on platelet surface for aggregation

Question 15

What are the drugs used to prevent platelet activation?

Answer 15

Prevent platelet activation/aggregation:
Clopidogrel; inhibits P2Y[12] receptor
Inhibits production of TXA2:
Aspirin-irreversible COX-1 inhibitor, used in high doses
Prevent platelet aggregation: 
Abciximab; inhibits GpIIb/IIIa

Question 16

When would you use antiplatelet drugs?

Answer 16

In arterial thrombosis:
Acute coronary syndrome-MI
Atrial fibrillation-prophylaxis of stroke

Question 17

Describe the process of propagation

Answer 17

Large scale thrombin production

Thrombin converse fibrinogen into insoluble fibrin strands

Question 18

Why are thrombolytics only given in emergency situations?

Answer 18

Only given within 6-8 hours of stroke otherwise they are less effective and the major side effect is bleeding. The patient after this time is more likely to die from bleeding.

Question 19

Give an example of a thrombolytic drug

Answer 19

Alteplase (IV): converts plasminogen into plasmin. Plasmin is a protease which degrades fibrin.
Recombinant type plasminogen activator
Used in strokes or ST elevated MI