Anticoagulant drugs Flashcards
What are the 2 main types of thrombosis ?
Arterial:
- Coronary, cerebral, peripheral
Venous:
- DVT and PE
What type of stroke are people with AF at risk of developing ?
Cardioembolic stroke - fibrin rich (think it still affects arteries here but its caused by venous factors mainly stasis from the abnormal heart muscle contraction so forms a fibrin type clot (virchows triad) which can shoot up to the arteries in the cerebrum and cause a stroke
Aspirin for the acute 2wks followed by warfarin treatment (LMWH always given when starting warfarin)
What are the main indications for anti-coagulation therapy ?
- Venous thrombosis - DVT and PE
- Atrial fibrillation (AF)
In general what one of the 4 main components of clot formation and regulation do anti-coagulants affect ?
Secondary haemostasis - formation of the fibrin clot
Describe how AF increases the risk of stroke
- If you have atrial fibrillation your heart is not pumping as well as it should. The upper chambers of your heart contract and relax in an uncoordinated and irregular way due to abnormal electrical activity. If your heartbeat is irregular and fast, your heart may not have a chance to relax and empty properly before filling up with blood again. Blood can collect inside the upper chamber of the left side of Atrial fibrillation (AF) and stroke Atrial fibrillation is a type of irregular heartbeat. It means that your heart may not be pumping as well as it should. As a result, blood clots are more likely to form in your heart, increasing your risk of having a stroke.
- If blood clots form in your heart, there is a risk they can travel in your bloodstream towards your brain. If a clot blocks one of the arteries leading to your brain, it could cause a stroke or TIA.
What are the main types of anti-coagulant drugs we should know about ?
- Heparin
- Warfarin
- NOAG - particularly rivaroxiban
Describe the action of heparin
It potentiates (increases) the action of anti-thrombin which inhibits thrombin and factor Xa
What are the 2 different forms of heparin and how can heparin be given ?
- Can be given as IV or SC
- 2 forms are LMWH and unfractionated heparin
Is the action of heparin immediate or does it take time to work ?
Action is pretty much immediate (this is why its used often acutely)
Both LMWH heparin and unfractionated heparin act on thrombin (II) and Xa by potentiating the effect of anti-thrombin but which of the 2 clotting factors does LMWH and unfractionated heparin primarily act on ?
- LMWH acts more on Xa
- Unfractionated heparin acts more on thrombin
What is used to monitor someone on unfractionated heparin?
APTT - note that the PT if enough unfractionated heparin is given can become prolonged
What is used to monitor someone on LMWH ?
- No monioring is usually required
- Anti-Xa assay can be used though
What are the main complications from heparin use ?
- Bleeding risk - look out for unusual bleeding, malena, haematuria, heavy nosebleeds
- Heparin induced thrombocytopenia (HITT) - results in thrombosis formation due to antibodies binding to heparin and resulting in platelet activation and result in clot formation, the platelet count falls as a result of the clot formation leading to the thrombocytopenia
- Osteoporosis with long term use - this is why warfarin is more used long-term
How it the action of heparin reversed ?
- Usually just need to stop heparin use (as it has a short half life)
- But incases of severe bleeding then use protamine sulphate
When should you use unfractionated heparin instead of LMWH ?
- In patients with renal impairment or established renal failure (GFR<30)
- Patients with an increased bleeding risk (as you can reverse unfractionated more easily)
What is the mechanism of action of warfarin ?
Inhibition of vitamin K
Why does inhibition of vitamin K result in reduced clotting in warfarin use ?
Because vitamin K is required for the final carboxylation of clotting factors II (prothrombin), VII, IX and X, without this these clotting factors do not work as they need to be carboxylated to be able to bind to through calcium to phospholipid on platelets
What other important component in clotting is dependent on vitamin K and how is this relevant to the use of warfarin ?
Protein C and S
These are anti-coagulant defences and due to the fact they have a shorter half life than clotting factors II, VII, IX & X this results in the patient for the first few days being in a pro-coagulative state, which is why LMWH is given for the initial phase of starting on warfarin
What type of vitamin is vit K, where is it absorbed and what is required for its absorption and what is vitamin K obtained from?
- It is a lipid soluble vitamin
- Absorbed in the upper intestine
- Requires bile salts for absorption
- From green leafy veg in the diet and intestinal synthesis from bacteria
Why do you need to monitor warfarin therapy ?
Because it has a narrow therapeutic window
How should warfarin be taken ?
Orally at the same time everyday - 6pm usually recommended
How is warfarin therapy monitored ?
INR - International normalised ratio
Basically a standardised PT, allows for comparison of results between labs and standardizes reporting of the prothrombin time
What is the major adverse effect of warfarin?
Haemorrhage
What are the factors which might influence the risk of haemorrhage for someone on warfarin ?
- Intensity of anticoagulation
- Concomitant clinical disorders
- Concomitant use of other medications
- BEWARE DRUG INTERACTIONS
- Quality of management
What drug and foods do you need to avoid in someone on warfarin ?
General factors that may potentiate warfarin (not necessarily will affect INR tho) :
- liver disease
- P450 enzyme inhibitors (see below)
- cranberry juice
- drugs which displace warfarin from plasma albumin, e.g. NSAIDs
- inhibit platelet function: NSAIDs
INR affecting drugs in pic
What is the range of bleeding complications that can be seen in someone on anti-coagulants ?
Mild:
- skin bruising
- epistaxis
- haematuria
Severe:
- gastro-intestinal
- intracerebral
- significant drop in Hb
How is warfarin therapy reversed ?
- If INR <8 and no or minor bleeding then simply omit warfarin
- If INR >8 and no or minor bleeding then omit warfarin and give oral or IV vit K
- If someone is bleeding severely then use factor concentrates (II,VII, IX & X)
What is the normal INR levels for someone on warfarin?
- Usually 2-3
- But for more at risk patients then 3-4
How long does giving vitamin K take to work in reducing someones INR and how long does giving factor concentrates (II,VII, IX & X)?
6 hours
Factor concentrates work immediately
What are the 2 main types of NOAG (new oral anticoagulants)?
- Thrombin inhibitors e.g. Dabigatran
- Xa inhibitors e.g. Rivaroxaban, Apixaban
NOAG do what the name says they inhibit the clotting factor in there drug name
What is the mechanism of action of rivaroxiban ?
Directly inhibits clotting factor Xa
What is the main type of NOAG that we should really be aware of ?
Rivaroxiban - factor Xa inhibitor
How are NOAG taken and is there a way to reverse their action ?
- Oral and no monitoring required
- Less drug interactions
- Currently no specific antidote for reversal
When are NOAG used (mainly rivaroxiban)?
- Used instead of LMWH as prophylaxis in elective hip and knee replacement surgery
- Used for selected patients for stroke prevention in atrial fibrillation
- Used for treatment of DVT/PE
- Likely to be introduced to routine clinical practice in next few years
