Anti-Coagulant Drugs

Question 1

Indications for anti-coagulant drugs?

Answer 1

Venous thrombosis

Atrial fibrillation (AF) - use CHA2DS2VASc scoring system to determine risk

Question 2

General target of anti-coagulants?

Answer 2

Target the formation of the fibrin clot

Question 3

How does a thrombus form in the venous system?

Answer 3

A low P system

Platelets are not activated; instead, there is activation of the coagulation cascade, forming a thrombus that is rich in fibrin clot

Question 4

MoA of heparin?

Answer 4

Potentiates anti-thrombin, which inactivates thrombin and other clotting factors

It stabilises the anti-thrombin and thrombin, or factor Xa, complex

Question 5

Uses of heparin?

Answer 5

It has an IMMEDIATE EFFECT and is used both by itself and as a bridging therapy until warfarin starts to work

It is administered parenterally

Question 6

2 forms of heparin?

Answer 6

Unfractionated - mainly targets anti-thrombin III but also the other

Low molecular weight heparin (LMWH) - mainly targets factor Xa but also the other

Question 7

Monitoring of heparin?

Answer 7

Unfractionated heparin (uncommonly used now) - monitor APTT

LMWH - usually NO MONITORING REQUIRED, as it has a more predictable effect; this is its major advantage, although it also does not cross the placenta

NOTE - if enough heparin is given, both the PT and APTT will be prolonged; however, usually the APTT is the only value prolonged

Question 8

Complications of heparin use?

Answer 8

Haemorrhage

Heparin-induced thrombocytopaenia (HITT) - antibodies produced to platelet factor IV; monitor FBC in patients on heparin and suspect HITT is the PLT is reduced by >50%

Osteoporosis, with long-term use

Question 9

Reversal of heparin?

Answer 9

Stop the heparin - it has a short half-life

If severe bleeding, administer protamine sulphate (antidote), which reverses the effects of anti-thrombin:
• Complete reversal for unfractionated heparin
• Partial reversal for LMWH

Question 10

Specific situations where unfractionated heparin may be used?

Answer 10

Patients with a high risk of thrombosis AND bleeding

Question 11

What are the coumarin anti-coagulant drugs?

Answer 11

WARFARIN

Phenindione

Acenocoumarin, pheprocoumon

Question 12

MoA of coumarin anti-coagulants?

Answer 12

Vitamin K antagonists

Question 13

Function of vitamin K?

Answer 13

Responsible for carboxylation of the glutamic acid residues in factors II, VII, IX, X, as well as in Protein C and protein S

These coagulation factors are synthesised but are non-functional

Question 14

Absorption of vitamin K?

Answer 14

Fat-soluble vitamin absorbed in the upper intestine; absorption requires bile salts

Question 15

Why do patients actually enter a pro-thrombotic state when they initial begin warfarin therapy?

Answer 15

Protein C and Protein S also rely on vitamin K for carboxylation

So, warfarin initially reduces the natural anti-coagulant defenses, so heparin is given until the effect on factors II, VII, IX and X is greater than the effect on PS and PS

Question 16

3 phases of warfarin therapy?

Answer 16

Initiation - rapid vs slow:
• Rapid - acute thrombosis in hospital
• Slow - AF in the community, liver failure, malnourished patients, elderly patients

Stabilisation

Maintenance - dose is taken at the same time everyday (6pm is recommended)

NOTE - warfarin has a narrow therapeutic window so it must be monitored

Question 17

How is warfarin monitored?

Answer 17

INR (international normalised ratio)

Target INR is usually 2-3

Question 18

Major adverse effect of warfarin and factors that may increase this risk?

Answer 18

Haemorrhage:
• Intensity of anti-coagulation
• Concomitant clinical disorders
• Concomitant use of other medications (BEWARE DRUG INTERACTIONS)
• Quality of Mx

Question 19

Signs of bleeding complications?

Answer 19

Mild - skin bruising, epistaxis, haematuria

Severe - GI, intracerebral, significant drop in Hb

Question 20

How to reverse warfarin?

Answer 20

Options include:
• No action - if mild bleeding and INR in range
• Omit warfarin dose(s)
• Administer oral vitamin K
• Administer clotting factors (FFP or factor concentrates)

NOTE - clinical and lab assessment of response

Question 21

Mx of bleeding/

Answer 21

Depending on severity of bleeding and INR

Vitamin K takes 6 hours to act

Clotting factors have an immediate effect

Question 22

MoA of NOACs?

Answer 22

Dabigatran - thrombin inhibitor (factor II)

Rivaroxaban, apixaban - factor Xa inhibitors

Question 23

Advantages of NOACs?

Answer 23

Oral

No monitoring required

Less drug interactions

Question 24

Disadvantages of NOACs?

Answer 24

Currently no specific antidote for reversal, although one is being developed

Question 25

When are NOACs used?

Answer 25

Used instead of LMWH as prophylaxis in elective hip and knee replacement surgery Used for selected patients for stroke prevention in AF Used for treatment of DVT/PE NOTE - probably going to be introduced to routine clinical practice in next few years; NOACs are better even without the antidote