Week 1 Lecture 2.5 Haemostasis Part 3

Question 1

Anticoagulant effects of normal

endothelium

Answer 1

1. PGI (prostacyclin) synthesised by the endothelium is a potent vasodilator and has anti platelet
   effects
   AA PGG2 PGH2 PGI
2. ADP degradation
   prevents further platelet activation
3. Nitric Oxide is a platelet inhibitor as well as a vasodilator
4. No further TF; TFPI synthesis
5. tPA
6. THROMBOMODULIN (Natural anticoagulants)
7. Heparin/heparans (Natural anticoagulants)

Question 2

Thrombomodulin and Activation of Protein C

Answer 2

• Thrombomodulin = Thromb in modul ator

• Expressed on endothelium and binds
thrombin which then loses its
procoagulant effect

• Thrombin/Thrombomodulin complex
activates Protein C (an anticoagulant)

• Protein C, together with Protein S
inactivates co factors Va and VIIIa

Question 3

Soluble agents of anticoagulation

Answer 3

Where the blood vessel is intact, the blood flows adjacent to the wound therefore free thrombin and other factors can be washed downstream

Question 4

Antithrombin

Answer 4

•Acts against thrombin as well as activated
factors Xa , IXa and XIa .

• Binds irreversibly with the activated factors
• Requires heparin as a catalyst
• The heparin comes from the endothelium

Question 5

Fibrinolysis

Answer 5

Removal of clot by breakdown of fibrin by plasmin

Question 6

Fibrinolysis

Answer 6

•The specificity of action of this pathway is increased by binding of tPA and plasminogen to fibrin as the clot is being formed

•Bound tPA is much more effective than unbound, thus
preventing plasmin being formed away from the clot

• The inhibitors of tPA and plasmin, PAI and alpha 2 antiplasmin do not work as well when their substrates are bound to fibrin
• Both tPA and PAI are synthesised in the endothelium