Haemeostasis and Thrombosis

Question 1

What is the difference between haemostasis and thrombosis?

Answer 1

Haemostasis is a physiological process that prevents excessive blood loss
Thrombosis is pathophysiological - a blood clot is forming but not always in response the vessel rupture

Question 2

What are venous clots described as and why?

Answer 2

-red thrombi as they contain a lot of erythrocytes and fibrin

Question 3

What are arterial clots described as and why?

Answer 3

• white thrombi because of macrophages entering the lesion and becoming foam cells
• also have a higher platelet component

Question 4

What are the initial stages of thrombosis?

Answer 4

1. tissue factor bearing cells activate factors X and V forming prothrombinase complex
2. The prothrombinase complex activates factor II (prothrombin) creating factor IIa (thrombin)
3. Antithrombin inactivates fIIa and fXa

Question 5

What does dabigatran do?

Answer 5

• inhibit factor IIa

- oral

Question 6

What does rivaroxaban do?

Answer 6

• inhibit factor Xa

- oral

Question 7

What does heparin do?

Answer 7

• activates antithrombin to decrease flla and fXa

- low molecular weight heparins e.g. dalteparin decrease fXa

Question 8

What does warfarin do?

Answer 8

• oral
• vitamin K agonist
• needed for generation of factors II, VII, IX and X

Question 9

What are the three factors in Virchows triad?

Answer 9

• rate of blood flow
• consistency of blood
• blood vessel wall integrity

Question 10

Why would rate of blood flow increase the risk of thrombosis formation?

Answer 10

-is blood is slow or stagnating there is no replenishment of anticoagulant factors and balance adjusted in favour of coagulation

Question 11

Why would consistency of blood increase the risk of thrombosis formation?

Answer 11

-imbalance between pro-coagulation and anticoagulation factors

Question 12

Why would blood vessel wall integrity increase the risk of thrombosis formation?

Answer 12

damaged endothelia will expose the blood to pro-coagulation factors

Question 13

What is the second stage of thrombosis?

Answer 13

amplification

Question 14

What happens during amplification?

Answer 14

1. thrombin (IIa) activates platelets

2. the activated platelets then change shape and become sticky, attaching to other platelets

Question 15

How does platelet activation occur molecularly?

Answer 15

• thrombin binds to PAR, which leads to a rise in intracellular Ca2+. This leads to the exocytosis of ADP from granules
• ADP activates P2Y12 receptors, which causes platelet activation
• PAR activation liberates arachidonic acid and COX generates thromboxane from AA
• thromboxane activation leads to expression of GPIIb/IIIa which is involved in platelet aggregation

Question 16

What does clopidogrel do?

Answer 16

-prevent platelet aggregation

ADP receptor antagonist

Question 17

What does aspirin do?

Answer 17

• inhibit thromboxane production

- COX-1 inhibitor

Question 18

What does abciximab do?

Answer 18

• prevent platelet aggregation

- IV,SC

Question 19

What is the third stage of thrombosis called?

Answer 19

-propagation stage

Question 20

What happens in the propagation stage?

Answer 20

1. the activated platelets mean that there is large-scale thrombin production
2. thrombin (IIa) binds to fibrinogen and converts to fibrin strands

Question 21

What do thrombolytics do?

Answer 21

• convert plasminogen to plasmin
• plasmin degrades fibrin

-alteplase is a recombinant tissue type plasminogen activator

Question 22

Summarise which type of drug are used where?

Answer 22

initiation- anticoagulants
amplification - antiplatelet
propagation - thrombolysis