Anti-Coagulants Flashcards
Action of Apixaban?
How is it best monitored?
it is a DIRECT inhibitor of factor Xa (10a)
Although it prolongs the PT, its effect is best measured using factor Xa assay.
Heparin mechanism?
Heparin molecules bind to antithrombin, inducing a conformational change that accelerates its rate of action about 1000-fold.
Antithrombin inhibits several of the clotting factors, most importantly, thrombin (factor IIa) and
factor Xa.
LMWH mechanism of action?
These complex with antithrombin and primarily inactivate factor Xa, including that located on platelet surfaces
Heparin & LMWH elimination?
Renal elimination therefore should be monitored and adjusted in renal impairement.
How does heparin-induced thrombocytopenia occur?
This typically starts between 5-14 days after starting heparin. Where there has been previous exposure to heparin, it can be quicker.
Heparin binds to platelet factor 4 (PF4), and antibodies develop to the heparin/PF4 complex and bind to it.
These antibodies also bind to platelets causing clumping and activation of platelets, resulting in the formation of both intra-arterial and venous thrombosis.
What makes unfractionated heparin unpredictable?
Binds to many proteins that neutralize its activity, thereby causing resistance to the drug and unpredictable pharmacokinetics.
Note that heparin, therefore, has a longer half-life in patients with hepatic cirrhosis. This zero order metabolism is rapidly saturable
Dabigatran mechanism? how is it best monitored?
DIRECT THROMBIN INHIBITOR
It is a prodrug converted to its active form by esterase-catalysed hydrolysis in the liver and plasma.
It prolongs prothrombin time (PT) and activated partial thromboplastin time (aPTT), but thrombin time (TT) or ecarin clotting time (ECT) is best for quantifying the effect.
Fondaparinux mechanism of action?
INDIRECT FACTOR 10A INHIBITOR
Fondaparinux is a synthetic pentasaccharide anticoagulant.
binding of fondaparinux to antithrombin enhances the inhibitory activity against factor Xa only, in contrast to the non-specific enhancement induced by heparin binding.
Which factors require vitamin k for synthesis by the liver?
factors II, VII, IX and X
2, 7, 9, 10
Warfarin mechanism of action?
Vitamin K epoxide reductase is inhibited by warfarin.
Warfarin treatment results in the production of clotting factors with diminished activity (10-40% of normal).
How can Warfarin be reversed?
Urgently: prothrombin complex concentrate (PCC)
Not urgent: A dose of 0.5 mg vitamin K (phytomenadione) is likely to reduce an excessive INR of 5 into the therapeutic range within a few hours.
Why is bridging therapy required whilst Warfarin therapy is being initiated?
Warfarin also decreases protein C and protein S levels when treatment first begins.
Protein C has a relatively short half-life and this can create a hypercoagulable state until the other vitamin K-dependent factors start to be depleted.
This is why an alternative anticoagulant should be used in conjunction with warfarin until INR>2.
Warfarin protein binding?
99% to albumin
How is Warfarin metabolised?
The products of warfarin metabolism are catalyzed by the CYP450 system and are inactive.
After conjugation to glucuronic acid, they are excreted in urine and faeces.
What constitutes prothrombin complex concentrate?
Modern PCCs such as Beriplex® and Octaplex® contain Factors II, VII, IX and X and so can provide immediate and predictable correction of excessive warfarin effect back to the therapeutic range or, in larger doses, to normal coagulation.
The effect of the PCC begins to wear off after 6-12 hours and so they are commonly used in combination with small doses of vitamin K to provide longer term correction.
