Blood thinners

With warfarin, what is the INR we need to maintain for VTEs, AF, cardioversion, MI and cardiomyopathy?

2.5

With warfarin, what is the INR we need to maintain for recurrent VTEs or mechanical heart valves?

3.5

How do you manage a major bleed in a patient on warfarin?

• Stop warfarin

• Give IV phytomenadione (vitamin K) and dried prothrombin complex (PCC - factors II, VII, IX and X)

How do you manage INR > 8 with minor bleeding?

• Stop warfarin

• Give IV phytomenadione

How do you manage INR > 8 with no bleeding?

• Stop warfarin

• Give oral phytomenadione

How do you manage INR 5-8 with minor bleeding?

• Stop warfarin

• Give IV phytomenadione

How do you manage INR 5-8 with no bleeding?

Withhold 1-2 doses of warfarin

When should warfarin be restarted after holding for high INR?

Restart warfarin when INR < 5

How frequently should INR be monitored when starting warfarin and when stable?

INR should be monitored every 1-2 days in early treatment, then every 12 weeks

What are the MHRA warnings with warfarin? (list the 2)

1. Reports of calciphylaxis (vascular calcification) - consult doctor if patient develops a painful skin rash/necrosis. Observed in patients with end stage renal disease but can also occur with normal renal function.

2. Drug interaction with tramadol - risk of increased INR leading to life threatening bruising and bleeding. Consider dose adjustments and/or additional INR monitoring

In which trimesters is warfarin contraindicated?

First and third trimesters.

What advice should be given to women of childbearing potential taking warfarin?

Use effective contraception during treatment due to dangers of teratogenicity

What are the main warfarin interactions and what is the nature of these interactions? (five)

• Tramadol - increases INR

• Miconazole (including oral gel) - increases INR

• Cranberry juice - increases INR

• CYP450 enzyme inhibitors and inducers - inhibitors increase INR and inducers decrease INR

• Vitamin K rich foods i.e leafy greens - avoid major changes in diet as it can reduce warfarins efficacy

At what INR can minor procedures with low bleeding risk be safely performed on warfarin and when should warfarin be restarted?

INR < 2.5

Restart within 24 hours of the procedure

When should warfarin be stopped before procedures with a high risk of bleeding / elective surgery?

Stop warfarin 5 days before.

When should vitamin K (phytomenadione) be given before surgery with risk of severe bleeding?

When INR ≥ 1.5

When should warfarin be restarted after surgery?

Evening of surgery or the next day if haemostasis is adequate

Which patients on warfarin require bridging anticoagulation / therapy?

High thromboembolic risk patients e.g.:

• VTE within last 3 months

• AF with previous stroke/TIA

• Mechanical mitral valve

What drug is used for bridging and how is this given (before and after surgery)?

Treatment dose LMWH.

Stop at least 24 hours before surgery.

Restart at least 48 hours after surgery if high bleeding risk

How is warfarin managed for emergency surgery if it can be delayed 6-12 hours?

Give IV vitamin K (phytomenadione)

How is warfarin managed for emergency surgery if it cannot be delayed 6-12 hours?

Give IV vitamin K (phytomenadione) PLUS dried prothrombin complex and check INR before surgery

What is the MOA for all the DOACs?

Apixaban, edoxaban and rivaroxaban are all direct and reversible inhibitors of factor Xa.

Dabigatran is a reversible inhibitor of free thrombin.

What are the MHRA warnings for DOACs?

• Higher risk of DOAC toxicity in patients with renal impairment - dose reductions may be needed based on medication and degree of impairment

• DOACs not recommended for patients with antiphospholipid syndrome - switch to vit k antagonist e.g. warfarin

What are the treatment and prophylactic doses of apixaban for VTE?

Include VTE prophylaxis doses following hip and knee replacement.

Treatment of VTE: 10mg BD 7 days, then 5mg BD

Prophylaxis of VTE: 2.5mg BD

• Hip replacement: 2.5mg BD for 32-38 days

• Knee replacement: 2.5mg BD for 10-14 days

What are the prophylactic doses of apixaban for stroke and systemic embolism in non-valvular AF?

5mg BD

When do we reduce apixaban dose in stroke and systemic embolism?

At least 2 of the following:

• Age 80+

• Body weight ≤ 60kg

• Serum creatinine of 133micromol/L or more

OR CrCl < 15-29 mL/min

What is the antidote for apixaban?

Andexanet alfa

What are the treatment and prophylactic doses of edoxaban for VTE?

And what is the stroke / systemic embolism prophylaxis dose in AF?

Treatment of VTE: 60mg OD following 5 day use of parenteral anticoagulation

Prophylaxis of VTE: 60mg OD following 5 day use of parenteral anticoagulation

Prophylaxis of stroke / systemic embolism in AF: 60mg OD

When is edoxaban dose reduced and what is the reduction?

Use a dose of 30mg OD if:

• Weight ≤ 60kg

• Moderate - severe renal impairment: CrCl 15-50 mL/min

What is the antidote for edoxaban?

There is none!

What are the treatment and prophylactic doses of rivaroxaban for VTE?

Include VTE prophylaxis doses following hip and knee replacement.

Treatment of VTE: 15mg BD for 21 days, then 20mg OD.

Prophylaxis of VTE: 10mg OD, increased to 20mg OD in high risk patients.

Hip replacement: 10mg OD for 35 days (5 weeks)

Knee replacement: 10mg OD for 14 days (2 weeks)

What is the stroke / systemic embolism prophylaxis dose in AF for rivaroxaban?

20mg OD

What is rivaroxaban prophylaxis dose if combined with aspirin or clopidogrel?

2.5mg BD

When is rivaroxaban dose reduced and what is the reduction?

Use a dose of 15mg instead of 20mg OD if:

• CrCl 15-49 mL/min

What is a key counselling point for rivaroxaban?

Take with or after food

What is the antidote for rivaroxaban?

Andexanet alfa

What are the treatment and prophylactic doses of dabigatran for VTE?

Include VTE prophylaxis doses following hip and knee replacement.

Treatment of VTE: 150mg BD following 5 day use of parenteral anticoagulation.

Prophylaxis of VTE: 150mg BD following 5 day use of parenteral anticoagulation.

Hip replacement: 220mg OD for 28-35 days.

Knee replacement: 220mg OD for 10 days.

What is the stroke / systemic embolism prophylaxis dose in AF for dabigatran?

150mg BD

When is dabigatran dose reduced and what is the reduction?

If aged 75-79 years or CrCl 30-50mL/min or at increased risk of bleeding:

• For knee and hip surgery, give 150mg OD instead of 220mg OD

• For all other indications, give 110-150mg BD instead of 150mg BD

If aged > 80 years, give 110mg

What is the antidote for dabigatran?

Idarucizumab

When is heparin (unfractionated) used? What must we monitor?

When a quick initiation and elimination is required.

Monitor APTT.

Why is LMWH preferred over unfractionated heparin?

• Lower risk of heparin induced thrombocytopenia (low platelet count which increases risk of bleeding)

• Longer duration of action

• Preferred in pregnanacy

What is the antidote for heparins?

Protamine sulphate

What are the contraindications of aspirin?

• Under 16 years due to risk of Raye’s syndrome unless indicated for Kawasaki disease

• Hypersensitivity to aspirin, salicylates or other NSAIDs

What happens with methotrexate and aspirin together?

Increased risk of MTX toxicity

What happens with omeprazole/esomeprazole and clopidogrel together?

Clopidogrel is a prodrug which requires activation by CYP2C19. Omeprazole is a strong inhibitor of CYP2C19 which reduces clopidogrel’s conversion to its active metabolite and therefore reduces its efficacy.

Use alternative PPI lansoprazole instead.