Anticoagulant Drugs Flashcards
What parts of the coagulation cascade are acted upon by heparin and warfarin?
Heparin - helps anti-thrombin
Warfarin - interrupts clotting factor synthesis
Heparin and Warfarin both have a narrow therapeutic window. What does this mean?
- small gap between effective dose and toxic dose
- same dose does not work for all patients (due to differing levels of Cytochrome P450 in the liver)
When should warfarin tablets be taken each day?
- no time specified, as long as tablet is taken at the same time each day
When are anticoagulants normally used?
- venous thrombosis
- AF stroke prophylaxis
How do doctors differentiate which stroke patients need anticoagulation and which need antiplatelets
- stroke in situ = atheroma rupture in vessel
=> antiplatelets req’d - stroke from AF = venous stasis
=> anticoagulation
Why can warfarin not be given immediately after a venous event and must be covered by heparin?
- initially drops protein C/S levels (as these are dependent on the vitamin K warfarin is antagonising)
- dropping these levels puts patients in a PROTHROMBOTIC state (i.e. more likely to clot)
=> need to cover with heparin whilst this occurs
What are the aims of Heparin?
- prevent clot extending in vessel (getting larger)
- prevent embolus breaking off of clot and travelling in body
How can Heparin be given?
IV (usually unfractioned heparin)
S/C (usually LMWH)
Explain how heparin works with antithrombin to prevent clotting
- Antithrombin usually attaches to thrombin (or Factor Xa) to do its job
- Heparin binds to the antithrombin part of this complex to keep it stable
What is the difference between unfractioned and LMWH?
LMWH - works when antithrombin bound to Factor Xa
=> requires less monitoring than Unfractioned
Why is unfractioned heparin still used?
some patients may be prone to bleeding and to clotting
=> need to be on unfractionated heparin as the IV infusion can be stopped quickly if patient starts bleeding
The effects of the unfractionated heparin disappear within 30 mins (whereas LMWH would be much longer)
How is treatment with heparin usually monitored?
Unfractionated = APTT
- as thrombin is responsible for activating FVIII/IX
=> APTT more sensitive than PT
Anti-Xa assay for LMWH
- only used in pregnancy as this can increase renal heparin clearance
What are the main complications of Heparin use?
- Bleeding
- Heparin induced thrombocytopenia (HITT)
=> Ab to platelets so they aggregate and can cause clots! - Osteoporosis with long term use
How can the effects of Heparin tx be reversed?
Stop the heparin
In severe bleeding -
Antidote = Protamine sulphate
=> Reverses antithrombin effect (only partial reversal in LMWH)
What is meant by a Coumarin Anticoagulant drug and how does it work?
Drug e.g. warfarin
Mechanism of action => inhibition of vitamin K
How is Vitamin K usually absorbed?
- Fat soluble vitamin (can be found in diet or made in gut)
- Absorbed upper intestine
- Requires bile salts for absorption
What is the main role of vitamin K in clotting?
- Final carboxylation of clotting factors II, VII, IX and X
=> makes the negative charged carboxyl groups that will eventually be attracted to the Ca2+ outer layer of the clot
For how long should a patient be anticoagulated if they have experienced their first VTE?
3-6 months
- long term if recurrent
HOw is warfarin therapy monitored?
INR (International Normalised Ratio)
INR = Patient’s PT in Seconds/ Mean Normal PT in Seconds
(also then standardised with ISI)
What factors can increase the risk of a patient bleeding on warfarin?
- Intensity of anticoagulation
- Other clinical disorders or medications
- BEWARE DRUG INTERACTIONS
=> less cytochrome p450 left behind after metabolising other drugs means less metabolism of warfarin => increased bleeding risk
What bleeding complications can occur in warfarin use?
MILD:
bruising
epistaxis
haematuria
SEVERE
GI
Intracerebral
Drop in Hb
How can the effects of warfarin be reversed?
If INR is HIGH (i.e. increased bleeding risk)
=> omit warfarin doses
=> takes 2-3 days for clotting factors to increase and INR to decrease
Give oral vitamin K to reverse antagonising warfarin effect
=> takes around 6 hours to reverse effect
Administer clotting factor concentrates
=> immediate effect but should only be used in emergencies
What are the new oral anticoagulants directed at in the coagulation cascade
- Oral direct thrombin inhibitors (less commonly used)
- Oral Xa inhibitors
What problems can occur with the Oral direct thrombin inhibitors?
- may cause deranged LFTs
- not suitable in patients with poor renal function as the drugs are renally metabolised and excreted
What is the main advantage of the Direct Factor Xa inhibitors and give examples of these drugs
- No monitoring is required
- Rivaroxaban, Apixaban, Edoxaban
What are Factor Xa inhibitors now being used for?
- prophylaxis before elective hip/knee replacement surgery
- Tx of DVT/PE as can be used immediately (no heparin cover)
- 1st line for AF stroke prevention
When is warfarin still used?
- patients with metal heart valves
- antiphospholipid Ab syndrome (due to slight arterial effect)
