Week 3- anticoagulant drugs

Question 1

What are the indications for anti-coagulant drugs?

Answer 1

Venous thrombosis

Atrial fibrillation

Question 2

What do anticoagulant drugs target?

Answer 2

Target formation of the fibrin clot.

Question 3

What does heparin do?

Answer 3

It potentiates antithrombin. Meaning it makes it more affect.

Question 4

How quick is heparins effect?

Answer 4

It has an immediate effect.

Question 5

What forms can heparin come in?

Answer 5

Unfractioned

Low molecular weight.

Question 6

How does heparin work?

Answer 6

It binds to antithrombin II. By doing this, it causes a conformational change in its active site to increase it, meaning it can bind more of factor Xa and thrombin. This can increase antithrombins effectiveness by 1000 fold.

Question 7

How do you monitor heparin?

Answer 7

Have to look at activated partial thromboplastin time for unfractioned (should be prolonged under heparin use due to antithrombin becoming more affective and binding factor X and thrombin).

(remember thrombin causes amplification of the clotting cascade, but if its bound too it won’t be able to do this anymore).

Question 8

Complications of heparin?

Answer 8

Bleeding
Heparin induced thrombocytopenia - have to monitor FBC in patients on heparin.
Osteoporosis in long term use.

Question 9

How do you reverse the effect of heparin?

Answer 9

By stopping the drug- it has a short half life so this should be sufficient.

Question 10

How might heparin reversal management differ in severe bleeding?
Does it work the same on unfractioned as LMWH?

Answer 10

Protamine sulphate- it reverses antithrombins affect.

It reverses the effects of unfractioned heparin completely but only partially reverses the affects of LMWH.

Question 11

What are coumarin anticoagulants?

Answer 11

Groups of drugs that work by inhibiting vitamin K. Made up of warfarin, phenindione, acenocoumarin and phenprocoumon

Question 12

What is vitamin K?

Answer 12

A fat soluble vitamin that is absorbed in the upper GI tract. It requires bile salts for absorption.

Question 13

Which clotting factors does vitamin K carboxylate?

Answer 13

X, IX, VII and II.

Also protein C and protein S are dependent on it.

Question 14

What does vitamin K carboxylate in the clotting factors?

Answer 14

Glutamic acid residues

Question 15

What is the significance of the carboxylation of the clotting factors?

Answer 15

Without the second carboxyl group, the clotting factors will not be negatively charged and cannot therefore adhere to the platelet plugs positively charged calcium surface.

Question 16

How should you initiate warfarin therapy?

Answer 16

Can be rapid or slow depending on the scenario.
Rapid would be in acute thrombosis in hospital
But slow would be for community initiation, in the elderly, liver failure etc.

Question 17

How do you maintain stability on warfarin therapy as a patient?

Answer 17

Dose should be taken at the same time every day (recommended 6pm).

Question 18

What is INR?

Answer 18

International normalised ratio.
Calculated by doing the patients prothrombin time over the mean normal prothrombin time in seconds. All of this is put to the power of ISI.

Question 19

What is ISI?

Answer 19

The international sensitivity index. Each thromboplastin is assigned an ISI which reflects the sensitivity of the thromboplastin to warfarin mediated reduction of vitamin K dependent clotting factors.

Question 20

A higher ISI means what?

Answer 20

Higher ISI, the less sensitive the thromboplastin is to warfarin mediated reduction of vitamin K dependent clotting factors.

Question 21

What is the significance of INR?

Answer 21

It allows adjusted viewing of patients bloods to the specific medication they are on, that is constant across labs and districts.

Question 22

What is the major adverse effect of warfarin?

Answer 22

Bleeding.

Question 23

What can affect the risk of bleeding on warfarin therapy?

Answer 23

Intensity of anticoagulation
Concomitant clinical disorders
Concomitant use of other medications
Drug interactions
Quality of management

Question 24

Name some mild bleeding complications?

Answer 24

Skin bruising
Epistaxis
Haematuria

Question 25

Name some serious bleeding complications?

Answer 25

Gastrointestinal
Intracerebral
Significant drop in Hb

Question 26

How do you go about warfarin reversal?

Answer 26

Watch and wait at first
Then omit a dose of warfarin
If this doesn’t work give oral vitamin K
If this doesn’t work give clotting factors (FFP or factor concentrates)
Clinical and laboratory assessment for response.

Question 27

How long does it take for oral vitamin K to reverse the warfarin affects?

Answer 27

6 hours.

Question 28

How long does it take for clotting factors to reverse warfarin affects?

Answer 28

Immediately.

Question 29

What does the management of bleeding depend on?

Answer 29

The severity of the bleed

The INR.

Question 30

Where do the newer oral anticoagulants act?

Answer 30

Can directly inhibit thrombin

Or directly inhibit factor Xa.

Question 31

Give an example of a thrombin inhibitor?

Answer 31

Dabigatran.

Question 32

Give examples of factor Xa inhibitors?

Answer 32

Rivaroxaban, apixaban

Question 33

Do the newer anticoagulants require monitoring?

Answer 33

No, no monitoring is required.

Question 34

Name one benefit and one con to newer anticoagulant therapies?

Answer 34

Benefit- less drug interactions

Con- no reverse

Question 35

When would you use newer anticoagulants?

Answer 35

Instead of LMWH in elective hip and knee replacement surgeries.
Used in selected patients for stroke prevention in a fib
Used for treatment of DVT/PE