Antithrombotic agents

Question 1

What do anticoagulants do?

Answer 1

Inhibit one or several components of the coagulation cascde

Question 2

What do fibrinolytic agents do?

Answer 2

Enhance lysis (breakdown) of the fibrin clot

Question 3

What do anti-platelets do?

Answer 3

Inhibit platelet activation or aggregation

Question 4

What is the mechanism of action of heparins and fondaparinux?

Answer 4

• Antagnoise Factor Xa (±thrombin)

* Act via antithrombin

Question 5

What is the mechanism of action of warfarin?

Answer 5

• Antagonise vitamin K

* Lowers factors II, VII, IX and X

Question 6

What is the mechanism of action of rivaroxoaban and apixaban?

Answer 6

Xa inhibitor

Question 7

What is the mechanism of action of Dabigatran?

Answer 7

IIa inhibitor

Question 8

Explain the characteristic of the heparins

Answer 8

• Do not cross the placenta
• Short half life
• Administered parenterally (no oral option)

Question 9

What are the differences between unfractionated heparin and LMWH?

Answer 9

• 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

Question 10

What are the side effects of the heparins?

Answer 10

• Heparin induced thrombocytopenia
• Osteoporosis
• Hyperkalaemia

Question 11

What are the indications of heparin?

Answer 11

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)

Question 12

How does warfarin antagonise vitamin k?

Answer 12

It inhibits vitamin K oxide reductase

Question 13

Which factors are affected by warfarin?

Answer 13

• II
• VII
• IX
• X

Question 14

Describe the characteristics of warfarin

Answer 14

• 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

Question 15

How long does it take to reach a steady state of warfarin?

Answer 15

5-7 days

Question 16

Explain the therapeutic window of warfarin

Answer 16

• 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

Question 17

What are the indications of warfarin?

Answer 17

• Atrial fibrillation
• Risk resection of a recurrent/fatal PE
• Prosthetic heat valve
• Not for immediate anticoagulation or short term thromboprophylaxis

Question 18

What are the contra-indications for the DOACs?

Answer 18

• Pregnancy and breast feeding
• Liver disease with cirrhosis ± coagulopathy
• Some drugs

Question 19

What are the side effects of the DOACs in comparison to those of warfarin?

Answer 19

• Fewer intracranial haemorrhage

* With dabigatran and rivaroxaban there is possibly more GI bleeds

Question 20

What are the differences between the onset and offset of the DOACs vs warfarin?

Answer 20

• 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

Question 21

What are the pros of warfarin?

Answer 21

• Slow onset and offset results in smooth anticoagulation
• Rare side effects other than bleeding
• Rapid reversal with vitamin K and PCC

Question 22

What are the cons of warfarin?

Answer 22

• Requires very individualised dosing
• Many drug, food and alcohol interactions
• Renal impairment may increase bleed risk
• Requires INR monitoring

Question 23

What are the pros of the DOACs?

Answer 23

• 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