WARFARIN

Question 1

INDICATION + DOSE

Answer 1

Prophylaxis of embolisation in rheumatic heart disease and atrial fibrillation,
Prophylaxis after insertion of prosthetic heart valve,
Prophylaxis and treatment of venous thrombosis and pulmonary embolism,
Transient ischaemic attacks

• Initially 5–10 mg, to be taken on day 1;
• Maintenance 3–9 mg daily, to be taken at the same time each day.

Subsequent doses dependent on the prothrombin time, reported as INR (international normalised ratio)

Question 2

MODE OF ACTION ( Vit K antagonist)

Answer 2

Warfarin and related vitamin K antagonists (VKAs) block the function of the vitamin K epoxide reductase complex in the liver, leading to depletion of the reduced form of vitamin K that serves as a cofactor for gamma carboxylation of vitamin K-dependent coagulation factors

Warfarin blocks one of the enzymes (proteins) that uses vitamin K to produce clotting factors. This disrupts the clotting process, making it take longer for the blood to clot.

Question 3

if patients are switched from warfarin to a direct-acting oral anticoagulant (DOAC):

Answer 3

Warfarin treatment should be stopped before DOAC treatment is started to reduce the risk of over-anticoagulation and bleeding.

Question 4

MHRA/CHM advice: Warfarin

Answer 4

Warfarin: reports of calciphylaxis (July 2016)

Warfarin use may lead to calciphylaxis—patients should be advised to consult their doctor if they develop a painful skin rash;

if calciphylaxis is diagnosed, appropriate treatment should be started and consideration should be given to stopping treatment with warfarin.

The MHRA has advised that calciphylaxis is most commonly observed in patients with known risk factors such as end-stage renal disease, however cases have also been reported in patients with normal renal function.

Question 5

WARFARIN CONTRAINDICATIONS

Answer 5

• Avoid use within 48 hours postpartum
• hemorrhagic stroke
• significant bleeding

Question 6

COMMON SE

Answer 6

Hemorrhage

Question 7

PREGNANCY

Answer 7

For all vitamin K antagonists
Should not be given in the first trimester of pregnancy.

Warfarin, acenocoumarol, and phenindione cross the placenta with risk of congenital malformations, and placental, fetal, or neonatal haemorrhage, especially during the last few weeks of pregnancy and at delivery. Therefore, if at all possible, they should be avoided in pregnancy, especially in the first and third trimesters (difficult decisions may have to be made, particularly in women with prosthetic heart valves, atrial fibrillation, or with a history of recurrent venous thrombosis or pulmonary embolism).

Stopping these drugs before the sixth week of gestation may largely avoid the risk of fetal abnormality.

Question 8

Monitoring requirements

Answer 8

The base-line prothrombin time should be determined but the initial dose should not be delayed whilst awaiting the result.

It is essential that the INR be determined daily or on alternate days in early days of treatment, then at longer intervals (depending on response), then up to every 12 weeks.

Change in patient’s clinical condition, particularly associated with liver disease, intercurrent illness, or drug administration, necessitates more frequent testing.

Question 9

WARFARIN ONSET OF ACTION

Answer 9

take at least 48 to 72 hours for the anticoagulant effect

If an immediate anticoagulation effect is required, unfractionated or low molecular weight heparin must be given concomitantly.

Question 10

TARGET INR OF 2.5

Answer 10

• Treatment of DVT OR PE
• Atrial fibrillation
• Cardioversion
• dilated cardiomyopathy
• myocardial infarction

Question 11

TARGET INR OF 3.5

Answer 11

• Recurrent deep-vein thrombosis or pulmonary embolism in patients currently receiving anticoagulation and with an INR above 2;
• Mechanical prosthetic heart valves:

Question 12

SCENARIO 1 - Major bleeding

Answer 12

1) Stop warfarin sodium
2) give phytomenadione (vitamin K1) by slow intravenous injection; give dried prothrombin complex (factors II, VII, IX, and X);

if dried prothrombin complex unavailable, fresh frozen plasma can be given but is less effective

Question 13

SCENARIO 2 - INR >8.0, minor bleeding

Answer 13

1) Stop warfarin sodium
2) give phytomenadione (vitamin K1) by slow intravenous injection; repeat dose of phytomenadione if INR still too high after 24 hours
3) restart warfarin sodium when INR <5.0

Question 14

SCENARIO 3 - INR >8.0, no bleeding

Answer 14

1) stop warfarin sodium
2) give phytomenadione (vitamin K1) by mouth using the intravenous preparation orally [unlicensed use]
3) repeat dose of phytomenadione if INR still too high after 24 hours
4) restart warfarin when INR <5.0

Question 15

SCENARIO 4 - INR 5.0–8.0, minor bleeding

Answer 15

1) Stop warfarin sodium
2) give phytomenadione (vitamin K1) by slow intravenous injection
3) restart warfarin sodium when INR <5.0

Question 16

SCENARIO 5 - INR 5.0–8.0, no bleeding

Answer 16

1) withhold 1 or 2 doses of warfarin sodium

2) reduce subsequent maintenance dose

Question 17

Peri-operative anticoagulation

Answer 17

Warfarin sodium should usually be stopped 5 days before elective surgery

phytomenadione (vitamin K1) by mouth (using the intravenous preparation orally [unlicensed use]) should be given the day before surgery if the INR is ≥1.5.

If haemostasis is adequate, warfarin sodium can be resumed at the normal maintenance dose on the evening of surgery or the next day.

Question 18

WARFARIN TABLET COLOURS

WHITE
BROWN
BLUE
PINK

Answer 18

WHITE - 0.5 MG
BROWN - 1 MG
BLUE - 3 MG
PINK - 5MG