Antithrombotics 1 Flashcards
What is haemostasis?
A response to vessel injury which results in the formation of a clot
What are the 3 processes involved in haemostatsis?
- Vasoconstriction
- Platelet plug formation
- Coagulation
How is the platelet plug formed?
Exposed collagen binds to and activates platelets
Releases platelet factors
Attracts more platelets
Platelets aggregate and form plug
Which substance activates the coagulation system?
Tissue factor (TF)
Which protein converts fibrinogen to fibrin?
Thrombin
Which enzyme dissolves clots?
Plasmin
What is thrombin and what are its functions? (3)
Serine protease
1. Converts fibrinogen to fibrin
2. Activates platelets (activates PAR-1 receptor on platelets)
3. Wound healing and inflammation
Which pathway regulates coagulation?
Protein C pathway
Vitamin K dependant process
Activated protein C cleaves cofactors factor 8a and 5a
Describe protein C
Multi-domain protein
Disulphide linked heavy and light chains
Heavy chain (serine protease domain)
Gla domain (vitamin K dependant domain)
What activates the protein C pathway?
Activated when thrombin binds to thrombomodulin
How does thrombin-TM complex activate protein C pathway?
- TM occupies site in thrombin which blocks other thrombin-binding proteins
- Thrombin loses pro-coagulation proteins
- Thrombin becomes an activator of protein C
(Thrombin inhibitors e.g. AT3 and PCI can still inhibit TM-bound thrombin)
Describe the protein C anticoagulation pathway
Thrombin activates F8 and F5 to form F8a and F5a
Protein C inactivates F8a and F5a
Thrombin-Thrombomodulin complex activates protein C
What is thrombomodulin?
Type 1 transmembrane protein receptor
Present in all vascular endothelium
What is anti-thrombin III (AT3)?
AT3 is a serine protease inhibitor
Inactivates factor Xa and thrombin
Inhibits clot formation
How is Anti-thrombin III activated?
AT3 is activated by binding of heparin sulphate
What is thrombosis?
The formation of a clot in a blood vessel which obstructs the blood flow
Which fatal condition can deep vein thrombosis (DVT) lead to?
Pulmonary embolism
What is the primary trigger of arterial thrombosis?
Rupture of atherosclerotic plaque
Releases contents of plaque into lumen
Platelet rich thrombin form around ruptured plaque
What are some triggers of venous thrombosis?
- Abnormal blood flow
- Altered blood properties
- Alterations in endothelium
What is the main difference between venous and arterial thrombosis?
With venous thrombosis endothelium remains intact
Arterial thrombosis causes endothelium damage
