Anticoagulants Flashcards
Why are natural anti-coagulants important?
They prevent the spontaneous activation of coagulation and ensure coagulation is confined to the site of injury.
What are the 3 important natural anticoagulants?
Protein C, protein S and antithrombin
How is protein C activated and what does it do?
Protein C is activated to activated protein C (APC) when thrombin binds to thrombomodulin on the endothelial cell surface.
APC inactivated factors Va and VIIIa in the presence of a co-factor protein S.
What does antithrombin effect? How does it do this?
Antithrombin effects BOTH thrombin AND factor Xa, inactivating them both. Antithrombin is markedly potentiated by heparin: this occurs physiologically by the binding of antithrombin to endothelial cell-associated heparins.
What are the main anticoagulant drugs?
Heparin, warfarin and direct oral anticoagulants (DOACs).
What is heparin made of?
Mixture of glycosaminylglycan chains extracted from porcine mucosa.
What does heparin do?
Indirectly potentiates the action of antithrombin leading to the inactivation of thrombin and factor Xa. Inactivation of thrombin requires longer heparin chains to wrap around both the antithrombin and thrombin.
How is heparin administered?
Subcutaneous injection or intravenously.
Warfarin is derived from coumarin. How does it work?
It is a vitamin K antagonist that works by interfering with protein carboxylation. It therefore reduces synthesis of functions factors II, VII, IX and X by the liver.
How is warfarin administered? What needs to be done after administration?
It is given as an oral tablet and its anticoagulant effect needs to be monitored by regular blood testing.
Why may Warfarin take longer to take effect?
Rather than effecting existing factor molecules, it reduces the synthesis of new ones. Therefore it won’t have effect until the current factor molecules have been depleted/replenished.
How do DOACs work? Do they require monitoring?
They usually directly inhibit thrombin or factor Xa (i.e. without the involvement of antithrombin). They do not usually require monitoring.
