Antithrombotics 1

Question 1

What is haemostasis?

Answer 1

A response to vessel injury which results in the formation of a clot

Question 2

What are the 3 processes involved in haemostatsis?

Answer 2

1. Vasoconstriction
2. Platelet plug formation
3. Coagulation

Question 3

How is the platelet plug formed?

Answer 3

Exposed collagen binds to and activates platelets
Releases platelet factors
Attracts more platelets
Platelets aggregate and form plug

Question 4

Which substance activates the coagulation system?

Answer 4

Tissue factor (TF)

Question 5

Which protein converts fibrinogen to fibrin?

Answer 5

Thrombin

Question 6

Which enzyme dissolves clots?

Answer 6

Plasmin

Question 7

What is thrombin and what are its functions? (3)

Answer 7

Serine protease
1. Converts fibrinogen to fibrin
2. Activates platelets (activates PAR-1 receptor on platelets)
3. Wound healing and inflammation

Question 8

Which pathway regulates coagulation?

Answer 8

Protein C pathway
Vitamin K dependant process
Activated protein C cleaves cofactors factor 8a and 5a

Question 9

Describe protein C

Answer 9

Multi-domain protein
Disulphide linked heavy and light chains
Heavy chain (serine protease domain)
Gla domain (vitamin K dependant domain)

Question 10

What activates the protein C pathway?

Answer 10

Activated when thrombin binds to thrombomodulin

Question 11

How does thrombin-TM complex activate protein C pathway?

Answer 11

1. TM occupies site in thrombin which blocks other thrombin-binding proteins
2. Thrombin loses pro-coagulation proteins
3. Thrombin becomes an activator of protein C

(Thrombin inhibitors e.g. AT3 and PCI can still inhibit TM-bound thrombin)

Question 12

Describe the protein C anticoagulation pathway

Answer 12

Thrombin activates F8 and F5 to form F8a and F5a
Protein C inactivates F8a and F5a
Thrombin-Thrombomodulin complex activates protein C

Question 13

What is thrombomodulin?

Answer 13

Type 1 transmembrane protein receptor
Present in all vascular endothelium

Question 14

What is anti-thrombin III (AT3)?

Answer 14

AT3 is a serine protease inhibitor
Inactivates factor Xa and thrombin
Inhibits clot formation

Question 15

How is Anti-thrombin III activated?

Answer 15

AT3 is activated by binding of heparin sulphate

Question 16

What is thrombosis?

Answer 16

The formation of a clot in a blood vessel which obstructs the blood flow

Question 17

Which fatal condition can deep vein thrombosis (DVT) lead to?

Answer 17

Pulmonary embolism

Question 18

What is the primary trigger of arterial thrombosis?

Answer 18

Rupture of atherosclerotic plaque
Releases contents of plaque into lumen
Platelet rich thrombin form around ruptured plaque

Question 19

What are some triggers of venous thrombosis?

Answer 19

1. Abnormal blood flow
2. Altered blood properties
3. Alterations in endothelium

Question 20

What is the main difference between venous and arterial thrombosis?

Answer 20

With venous thrombosis endothelium remains intact
Arterial thrombosis causes endothelium damage