Flashcards in Anticoagulant Drugs Deck (76)
What are the 2 main groups of thrombotic events?
* Arterial: coronary, cerebral, peripheral.
* Venous: DVT, PE
What are i) arterial ii) venous clots rich in?
What are the 2 indications for anticoagulant drugs?
* Venous thrombosis.
* Atrial fibrillation.
What do anticoagulant drugs target?
The formation of fibrin clot.
What is NOT activated in the formation of a venous thrombosis?
Describe a venous thrombosis.
Activates coagulation cascade – so rich in fibrin clot
Platelets are more involved in arterial thrombosis – they stick to damaged atherosclerotic plaque
What risk is it important to prevent in those with AF?
Why is stroke more likely in someone with AF?
The atrium of the heart quivers, instead of contracting properly.
This results in blood stasis, and the formation of a fibrin-rich clot on the wall of the left atrium.
If this clot breaks off, it follows the path of least resistance through the left ventricle, up the aorta, into the carotid artery and eventually into the circulation of the brain where it causes a stroke.
What are the 2 main naturally occurring anticoagulants.
1. Serine protease inhibitors e.g. antithrombin
2. Protein C and protein S
Describe serine protease inhibitors.
Antithrombin switches off haemostasis by binding to and inactivating thrombin.
This results in the switching off of:
a. conversion of fibrinogen to fibrin.
b. positive feedback action of thrombin on both VIII/IXa and V/Xa.
Describe the function of Protein C and protein S.
Switch off factors V and VIII.
Activated when thrombin binds to thrombomodulin and changes its function.
What is the mechanism of action of heparin?
It potentiates antithrombin
Usually, antithrombin binds to thrombin/clotting factor Xa to switch them off. Heparin just makes this complex more stable, potentiating the effects of antithrombin.
What is the onset of effect like in heparin?
Via what route is heparin administered?
Parenterally – IV or SC
What are the 2 forms of heparin?
* Low molecular weight (LMWH)
In terms of mechanism, what is the difference between unfractioned heparin and LMWH?
Unfractionated – greater inhibition of thrombin
LMWH – greater inhibition of Xa. (Think abbreviations go together - LMWH + Xa)
What is used to measure unfractioned heparin?
Activated partial thromboplastin time (APTT)
- Generally want to get this to 1-1.5x normal to give a good anticoagulant effect
Is monitoring for LMWH needed? If so, what is used?
Not usually – due to its more predictable response (can give set dose depending on pt’s weight).
But if needed, and Anti-Xa assay can be used.
What is the main risk to worry about with heparin?
What is there a risk of developing, particularly with unfractionated heparin? Describe this.
Heparin induced thrombocytopenia (with thrombosis) – HITT
This is an immune reaction in which antibodies to one of the platelet factors is developed. It can result in catastrophic thrombosis.
How is HITT monitored for?
Monitor FBC in patients on heparin. (be worried if see platelet count drop by about half within 5-10d of starting heparin).
Give an alternative drug.
What is the main long term complication of long term use of heparin?
Why is heparin not generally used in the long term?
Needs to be injected, can cause osteoporosis with long term use
What works well if you need to reverse the effects of heparin?
Just stopping it – since it has immediate onset and offset.
Unfractionated heparin will be gone within half an hour.
What can be used in severe bleeding to reverse the effects of heparin?
Reverses antithrombin effect.
Does protamine sulphate work for both unfractioned and LMWH?
Yes – completely reverses unfractionated heparin, but only partial reversal for LMWH.
Give examples of coumarin anticoagulants.
What is the difference between coumarin anticoagulants and heparin?
Coumarin anticoagulants can be used longer term than heparin