CV: Anticoagulants

Question 1

The main use of anticoagulants is to prevent thrombus formation or extension of an existing thrombus in the slower-moving venous side of the circulation, where the thrombus consists of what?

Answer 1

The main use of anticoagulants is to prevent thrombus formation or extension of an existing thrombus in the slower-moving venous side of the circulation, where the thrombus consists of a fibrin web enmeshed with platelets and red cells.

Question 2

Anticoagulants are of less use in preventing thrombus formation in arteries. Why?

Answer 2

In faster-flowing vessels, thrombi are composed mainly of platelets with little fibrin.

Question 3

The oral anticoagulants warfarin sodium, acenocoumarol and phenindione, antagonise the effects of vitamin K, and take at least how long for anticoagulant effect to develop fully?

Answer 3

48 to 72 hours.

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

Question 4

Coumarins and phenindione should not be used in what as first-line therapy?

What should be used?

Answer 4

These oral anticoagulants should not be used in cerebral artery thrombosis or peripheral artery occlusion as first-line therapy; aspirin is more appropriate for reduction of risk in transient ischaemic attacks.

Question 5

An INR which is within how many units of the target value is generally satisfactory?

Answer 5

0.5 units within the target value.

Question 6

What is the target INR for MI?

Answer 6

2.5

Question 7

What is the target INR for recurrent DVT or PE in patients currently receiving anticoagulation and with an INR above 2?

Answer 7

3.5

Question 8

What is the target INR for AF?

Answer 8

2.5

Question 9

What is the target INR for the treatment of DVT or PE?

Answer 9

2.5

Question 10

What duration of treatment with warfarin is recommended for VTE provoked by surgery or other transient risk factor (e.g. COC use, pregnancy, plaster cast)?

Answer 10

3 months

Question 11

What duration of treatment with warfarin is recommended for isolated calf-vein deep-vein thrombosis?

Answer 11

6 weeks

Question 12

What duration of treatment with warfarin is recommended for unprovoked proximal DVT or PE?

Answer 12

At LEAST 3months; long-term anticoagulation may be required.

Question 13

What should be done for major bleeding with warfarin use?

Answer 13

Stop warfrain.
Give phytomednadione (Vit K) by slow intravenous injection.
Give dried prothrombin complex (factors II, VII, IX and X); if dried unavailable then fresh frozen plasma but it is less effective.

Question 14

What should be done for INR >8.0, minor bleeding?

Answer 14

Stop Warfarin, give vit K1 by slow IV injection.
Repeat the dose of vit k if the INR still too high after 34 hours;
Restart when INR <5

Question 15

What should be done for INR >8.0, no bleeding?

Answer 15

Stop warfarin, give vit k by MOUTH, repeat dose if INR still too high after 24 hours, restart when <5,0

Question 16

What should be done for INR 5.0-8.0, minor bleeding?

Answer 16

Stop warfarin.
Give Vit K by slow IV injection.
Restart warfarin when INR <5.0.

Question 17

What should be done when INR 5.0-8.0, no bleeding?

Answer 17

Withhold 1 or 2 doses of warfarin and reduce subsequent maintenace dose.

Question 18

Warfarin should usually be stopped how many days before elective surgery?

Answer 18

5 days.

Question 19

Warfarin sodium should usually be stopped 5 days before elective surgery; What should be given the day before surgery if the INR is >1.5?

Answer 19

Phytomenadione (vitamin K1) by mouth.

Question 20

Patients stopping warfarin sodium prior to surgery who are considered to be at high risk of thromboembolism (e.g. those with a venous thromboembolic event within the last 3 months, atrial fibrillation with previous stroke or transient ischaemic attack, or mitral mechanical heart valve) may require interim therapy (‘bridging’) with what?

Answer 20

LMWH which should be stopped at least 24 hours before surgery and if the surgery carries a high risk of bleeding, the LMWH should not be restarted until at least 48 hours after surgery.

Question 21

Patients on warfarin sodium who require emergency surgery that can be delayed for 6–12 hours can be given intravenous phytomenadione (vitamin K1) to reverse the anticoagulant effect. If surgery cannot be delayed, what can be given in addition to IV phytomenadione (vit K1)?

Answer 21

Dried prothrombin complex.

Question 22

How does warfarin work?

Answer 22

Warfarin inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S and protein Z.

The protein C and S inhibition can cause a transient increase in clotting when warfarin initiated.

Question 23

Which of the following can increase the anticoagulant effects of warfarin?

Metronidazole
St Johns Wort
Macrolides
Amiodarone 
Phenytoin

Answer 23

M-A-M:
Macrolides
Amiodarone
Metronidazole - all can increase anticoagulant effects of warfarin, increased INR.

St Johns Wort can increase the metabolism of warfarin so decreased anticoagulation and decreased INR.

Phenytoin induces CYP2A9, increased metablism of warfarin, lower INR.

So first, you may remember from pharmacology that warfarin is highly protein bound. This means that a lot of it is “inactive” as it’s floating around your blood stream because it is tied up and bound to your serum albumin. Quick side note: This is also why your warfarin patients with low albumin require smaller doses to achieve therapeutic INRs.

However, phenytoin is more protein bound than warfarin. When you start phenytoin, the first thing it does is kick a bunch of warfarin off of your serum albumin–essentially “activating” it. This will raise your patient’s INR. It will usually normalize out in a few days.

But we’re not done yet. Remember that phenytoin is a pretty strong CYP inducer across the board. So even while it’s kicking warfarin off of albumin, it’s ramping up production of 2C9 and 3A4–increasing the metabolism of warfarin. This will lower your patient’s INR.

You just have to monitor phenytoin carefully, as it’s likely every patient will respond differently. In general, expect an initial increase in INR, followed by a decrease about a week or so later. Once you get the patient therapeutic and stable on phenytoin, the drug interaction should normalize out.

Question 24

Heparin (unfractionated) has what onset of action and what duration of action?

Answer 24

Heparin initiates anticoagulation rapidly but has a short duration of action. It is often referred to as ‘standard’ or heparin (unfractionated) to distinguish it from the low molecular weight heparins, which have a longer duration of action.

Question 25

Which has a longer duration of action?

Heparin
LMWH

Answer 25

Heparin initiates anticoagulation rapidly but has a short duration of action. It is often referred to as ‘standard’ or heparin (unfractionated) to distinguish it from the low molecular weight heparins, which have a longer duration of action.

Question 26

Why might the use of heparin (unfractionated) be preferred over that of LMWHs?

Answer 26

Although a low molecular weight heparin is generally preferred for routine use, heparin (unfractionated) can be used in those at high risk of bleeding because its effect can be terminated rapidly by stopping the infusion.

Question 27

Why are LMWH (dalteparin, enoxaparin and tinzaparin) usually preferred over heparin in the prevention of VTE? (2)

Answer 27

They are just as effective BUT they have a lower risk of heparin-induced thrombocytopenia.

Also once-daily dosing is possible with some LMWH because of the longer duration of action, which makes them more convenient.

Question 28

Dalteparin and tinzaparin sodium are both licensed for the extended treatment and prophylaxis of VTE in patients with solid tumours. Treatment is recommended to last how long?

Answer 28

For a duration of 6 months.

Question 29

Name a heparinoid used for prophylaxis of DVT in patients undergoing general or orthopaedic surgery.

Why might it be used instead of Heparin/LMWHs?

Answer 29

Danaparoid sodium is a heparinoid used for prophylaxis of deep-vein thrombosis in patients undergoing general or orthopaedic surgery.

Providing there is no evidence of cross-reactivity, it also has a role in patients who develop heparin-induced thrombocytopenia.

Question 30

When would the anticoagulant drug Argatroban be used?

Answer 30

Anticoagulation in patients with heparin-induced thrombocytopenia type II who require parenteral antithrombotic treatment

Question 31

Bivalirudin is a hirudin analogue and thombin inhibitor. It has a use in what syndrome(s)?

Answer 31

Bivalirudin, a hirudin analogue, is a thrombin inhibitor which is licensed for unstable angina or non-ST-segment elevation myocardial infarction in patients planned for urgent or early intervention, and as an anticoagulant for patients undergoing percutaneous coronary intervention.

Acute Coronary Syndromes

Question 32

Eproprostenol (prostacyclin) can be given to inhibit platelet aggregation during _____ _____ when heparins are unsuitable or contra-indicated.

Answer 32

Epoprostenol (prostacyclin) can be given to inhibit platelet aggregation during renal dialysis when heparins are unsuitable or contra-indicated.

It is also licensed for the treatment of primary pulmonary hypertension resistant to other treatment, usually with oral anticoagulation; it should be initiated by specialists in pulmonary hypertension.

Epoprostenol is a potent vasodilator.

It has a short half-life of approximately 3 minutes and therefore it must be administered by continuous intravenous infusion.

Question 33

Epoprostenol (prostacyclin) can be given to inhibit platelet aggregation during renal dialysis when heparins are unsuitable or contra-indicated.

It is also licensed for the treatment of what?

Answer 33

It is also licensed for the treatment of primary pulmonary hypertension resistant to other treatment, usually with oral anticoagulation; it should be initiated by specialists in pulmonary hypertension.

Epoprostenol is a potent vasodilator.

It has a short half-life of approximately 3 minutes and therefore it must be administered by continuous intravenous infusion.

Question 34

Fondaparinux sodium is a synthetic pentasaccharide that inhibits what?

Answer 34

Activated factor X (Xa)