Warfarin (High Risk)

Question 1

What conditions is warfarin indicated for?

Answer 1

1) VTE - Warfarin is an option for treatment and prevention of recurrence (secondary prevention)
2) To prevent arterial embolism in patients with atrial fibrillation (AF) or prosthetic heart valves

Question 2

outline the MoA of warfarin

Answer 2

Warfarin inhibits hepatic production of vitamin K-dependent coagulation factors. It does this by inhibiting vitamin K epoxide reductase, the enzyme responsible for restoring vitamin K to its reduced form, necessary as a co-factor in the synthesis of these clotting factors.

Question 3

List the important adverse effects caused by warfarin

Answer 3

1) Bleeding
2) Increased risk of bleeding from minor trauma (e.g. intracerebral haemorrhage after minor head injury) and existing abnormalities such as peptic ulcers.
3) Severe over-warfarinisation can trigger spontaneous bleeding, such as epistaxis or retroperitoneal haemorrhage

Question 4

What drug can be used to reverse the effects of warfarin overdose?

Answer 4

Warfarin can be reversed with phytomenadione (vitamin K1) or dried prothrombin complex

Question 5

which patients should warfarin be used in caution in?

Answer 5

1) Contraindicated in patients at immediate risk of haemorrhage, including after trauma and in patients requiring surgery.
2) Patients with liver disease are less able to metabolise warfarin and are at increased risk of bleeding
3) Avoid use within 48 hours postpartum, hemorrhagic stroke, significant bleeding

Question 6

why should warfarin be avoided in pregnancy?

Answer 6

1) Avoid in first and third trimester due to a risk of teratogenicity (cardiac and cranial abnormalities) and neonatal hemorrhage
2) It should also be avoided later in pregnancy due to the risk of peripartum haemorrhage

Question 7

list some of the important interactions with regards to warfarin

Answer 7

1) Cytochrome P450 (CYP) inducers (e.g. phenytoin, carbamazepine, rifampicin) increase warfarin metabolism and risk of clots
2) CYP inhibitors (e.g. fluconazole, macrolides) decrease warfarin metabolism and increase bleeding risk.
3) Other antibiotics can increase the effect of warfarin by killing gut flora that synthesise vitamin K, but this is not usually a clinical problem.

Question 8

Warfarin has a low therapeutic index. explain what this means

Answer 8

The plasma concentration of warfarin required to prevent clotting is close to the concentration that causes bleeding

Question 9

What marker is used to guide the dosing of warfarin in patients?

Answer 9

International normalised ratio (INR)

Question 10

what time of the day is warfarin traditionally taken?

Answer 10

warfarin is taken each day at around 18:00 hours for consistent effects on the INR taken the following morning

Question 11

Outline the MHRA alert regarding Vitamin K antagonists

Answer 11

There is a risk of interaction and change in INR with vit k antagonists and direct acting antivirals used to treat chronic hepatitis C

Question 12

what counselling should women of child bearing age be given regarding warfarin?

Answer 12

dangers of teratogenicity

Question 13

how can the risk of fetal abnormalities be reduced in women taking warfarin?

Answer 13

1) Stopping warfarin before sixth week of gestation
2) babies of mothers taking warfarin at the time of delivery should be offered immediate prophylaxis with IM phytomenadione

Question 14

how often should INR be measured in those taking warfarin?

Answer 14

1) INR determined daily or on alternate days when the drug is initially initiated
2) Then longer intervals and up to every 12 weeks

Question 15

Outline the important MHRA alert regarding warfarin

Answer 15

use of warfarin may rarely lead to of calciphylaxis. Speak to GP if you develop skin rash especially if you have end stage renal disease