Anticoagulant drugs

Question 1

Why do heparin and warfarin need constant monitoring?

Answer 1

Narrow therapeutic window

Question 2

Name the two types of thrombotic events

Answer 2

arterial - atherosclerosis

Venous - stasis, fibrin clot

Question 3

What are the indications for anticoagulant drugs?

Answer 3

Venous thrombosis

Atrial fibrillation - blood clot on left atrial wall due to stasis caused by irregular contractions

Question 4

What is the consequence of atrial fibrillation?

Answer 4

Stroke

Embolus travels to cerebral circulation

Question 5

What are the naturally occuring anti-coagulants?

Answer 5

1. Serine protease inhibitors - anti thrombin binds to thrombin which prevents fibrinogen conversion to fibrin
2. Protein C and S - these are not usually targeted by drugs. Note that these are vit K (thus affected by warfarin)

Question 6

What is heparin?

Answer 6

potentiates antithrombin

immediate effect

Question 7

What route is heparin given?

Answer 7

Iv or SC

Question 8

What are the 2 forms of heparin?

Answer 8

Unfractionated (IV form)

Low molecular weight (LMWH)

Question 9

Why is LMWH preferred over unfractionated heparin?

Answer 9

Needs a lot more monitoring, LMWH is predictable and given based on patient’s weight

Question 10

What is the MOA of unfractionated heparin?

Answer 10

Unfractionated heparin joins antithrombin to thrombin forming a complex – potentiating effect

Question 11

What is the MOA of LMWH?

Answer 11

keps antithrombin and factor Xa together in a complex.

This prevents the conversion of prothrombin to thrombin

Question 12

How is heparin monitored?

Answer 12

APTT - for unfractionated

Anti Xa assay for LMWH - usually LMWH is not monitored (except in obesity and pregnancy)

Question 13

What are the complications for heparin?

Answer 13

Risk of bleeding - small compared to no treatment

HITT - antibodies to platelet fomring a complex. Platelets aggregate and then drop. risk of life threatening thrombosis

Osteoporosis with long term use - interferes with bone metabolism

Question 14

Patient on anticoagulants has a significant drop in platelet. What to check for?

Answer 14

Check for antibodies of Heparin induced thrombocytopenia

Question 15

Heparin reversal

Answer 15

Stop the heparin

In severe bleeding
Protamine sulphate (unfractionated heparin) reverses antithrombin effect.

Question 16

What is the role of protamine sulphate in unfractionated and LMWH?

Answer 16

Unfractionated = complete heparin reversal

LMWH = partial reversal

Question 17

List the coumarin anticoagulants

Answer 17

warfarin
phenindione
acenocoumarin
phenprocoumon

Question 18

Vitamin K and clotting

Answer 18

Fat soluble
Synthesised in liver
Required for the final carboxylation of clotting factors 2, 7, 9 & 10 - essential for function

Question 19

Where is warfarin metabolised?

Answer 19

Warfarin is metabolised in the liver

Question 20

Stages of warfarin therapy

Answer 20

Initiation - rapid or dlwo
Stabilisation
Maintenance

Question 21

What precaution to be taken when administering warfarin?

Answer 21

Narrow therapeutic window, hence close monitoring needed

Question 22

What is INR?

Answer 22

Ratio of prothrombin time calibrated for different reagents in different labs in order to standardise globally

Question 23

What is the major AE of warfarin?

Answer 23

BLEEDING

Question 24

List the features that influence bleeding risk when on warfarin

Answer 24

Intensity of anticoagulation
Concomitant clinical disorders
Concomitant use of other medications 
BEWARE DRUG INTERACTIONS
Quality of management

Question 25

What is the target INR?

Answer 25

2-3

Question 26

What are the mild complications of bleeding when on warfarin?

Answer 26

skin bruising epistaxis haematuria

Question 27

What are the severe complications of bleeding when on warfarin?

Answer 27

gastro-intestinal intracerebral significant drop in Hb

Question 28

How to reduce the effect of warfarin?

Answer 28

Increase Vit K (IV

Question 29

What to do if there is severe complications of bleeding when on warfarin?

Answer 29

Administer clotting factors (factor concentrates)

Question 30

Name the thrombin inhibitor that is renally metabolised and excreted

Answer 30

Dabigatran

Question 31

Why is dabigatran CI in elderly

Answer 31

Renal metabolism and excretion | UTI

Question 32

List the Xa inhibitors

Answer 32

edoxaban rivaroxaban apixaban

Question 33

What are the benefits of the new anti-coagulants

Answer 33

Direct thrombin inhibitors (dabigatran) Direct activated factor X inhibitors (eg edoxaban, rivaroxaban, apixaban) Oral and no monitoring required Less drug interactions Recently developed specific antidotes for reversal

Question 34

What is the indication of new anticoagulant drugs

Answer 34

Initially used instead of LMWH as prophylaxis in elective hip and knee replacement surgery Used for treatment of DVT/PE Stroke prevention in atrial fibrillation for new patients

Question 35

What is the treatment of choice in metal heart valves and anti-phospholipid syndrome?

Answer 35

Warfarin