Antithrombotic agents Flashcards
What do anticoagulants do?
Inhibit one or several components of the coagulation cascde
What do fibrinolytic agents do?
Enhance lysis (breakdown) of the fibrin clot
What do anti-platelets do?
Inhibit platelet activation or aggregation
What is the mechanism of action of heparins and fondaparinux?
- Antagnoise Factor Xa (±thrombin)
* Act via antithrombin
What is the mechanism of action of warfarin?
- Antagonise vitamin K
* Lowers factors II, VII, IX and X
What is the mechanism of action of rivaroxoaban and apixaban?
Xa inhibitor
What is the mechanism of action of Dabigatran?
IIa inhibitor
Explain the characteristic of the heparins
- Do not cross the placenta
- Short half life
- Administered parenterally (no oral option)
What are the differences between unfractionated heparin and LMWH?
- LMWH has a higher bioavailability and IV half life, lower protein binding
- LMWH does not require monitoring but unfractionated heparin requires APTT monitoring
- LMWH has lower risk of side effects
What are the side effects of the heparins?
- Heparin induced thrombocytopenia
- Osteoporosis
- Hyperkalaemia
What are the indications of heparin?
Provides an immediate but a short acting anticoagulant effect:
•Acute DVT or PE (LMWH)
•During cardiac bypass surgery (IV UFH)
•Acute coronary syndromes
•Medium term after VTE in cancer patients
•Prophylaxis against VTE in medical and post op and obstetric patients (LWMH)
How does warfarin antagonise vitamin k?
It inhibits vitamin K oxide reductase
Which factors are affected by warfarin?
- II
- VII
- IX
- X
Describe the characteristics of warfarin
- Delayed onset and offset
- Effective half life of approx 36 hours
- Higher inter-individual variability
- Narrow therapeutic window
- Many drug and food interactions
- Requires regular INR monitoring
How long does it take to reach a steady state of warfarin?
5-7 days
Explain the therapeutic window of warfarin
- Narrow window
- Usually INR 2.0-3.0
- Increasing the intensity of the anticoagulant, greatly increases the risk of a haemorrhagic event but decreasing leads to increased risk of a thromboembolic event
What are the indications of warfarin?
- Atrial fibrillation
- Risk resection of a recurrent/fatal PE
- Prosthetic heat valve
- Not for immediate anticoagulation or short term thromboprophylaxis
What are the contra-indications for the DOACs?
- Pregnancy and breast feeding
- Liver disease with cirrhosis ± coagulopathy
- Some drugs
What are the side effects of the DOACs in comparison to those of warfarin?
- Fewer intracranial haemorrhage
* With dabigatran and rivaroxaban there is possibly more GI bleeds
What are the differences between the onset and offset of the DOACs vs warfarin?
- For warfarin each dose builds up so a slow onset and it has a fairly quick offset
- DOACs have immediate effect with a very quick onset and also quick offset
What are the pros of warfarin?
- Slow onset and offset results in smooth anticoagulation
- Rare side effects other than bleeding
- Rapid reversal with vitamin K and PCC
What are the cons of warfarin?
- Requires very individualised dosing
- Many drug, food and alcohol interactions
- Renal impairment may increase bleed risk
- Requires INR monitoring
What are the pros of the DOACs?
- Rapid onset and offset so anti coagulated from within 3 hours of the first dose
- Does not require regular monitoring only an annual review
- Few drug and no food or alcohol interactions
