Anticoagulant Drugs

Question 1

What are indications for anticoagulant drugs?

Answer 1

Venous thrombosis

AF

Question 2

Why in an acute situation (DVT/ PE) must heparin be started alongside warfarin?

Answer 2

In the initial phases (2-3 days) of warfarin treatment levels of protein C and S will drop as they are also vitamin K dependent producing a prothrombotic state
Heparin acts instantly as an anticoagulant

Question 3

What is the mechanism of heparin?

Answer 3

Potentiates antithrombin

Question 4

What are the different forms of heparin?

Answer 4

Unfractionated; IV

LMWH; S/c

Question 5

Do anticoagulants dissolve clots?

Answer 5

No; they prevent them from getting bigger and will stabilize the clot

Question 6

What is the difference between unfractionated and LMWH heparin?

Answer 6

Unfractionated; binds to antithrombin - thrombin complex to stabilize it
LMWH; binds to antithrombin -10a complex to stabilise it

Question 7

Does heparin require monitoring?

Answer 7

Yes; only unfractionated
Monitor APTT
LMWH heparin does NOT require monitoring (but in pregnant women if required, can do assay of factor 10a)

Question 8

Why will IV unfractionated heparin be used over LMWH?

Answer 8

Renal failure

Can be stopped in event of bleeding, whereas LMWH will take around 6 hours to stop

Question 9

What is the difference in monitoring of warfarin and unfractionated heparin?

Answer 9

Prothrombin time (INR) = warfarin 
APTT = unfractionated heparin

Question 10

Why is APTT sensitive for heparin if it will affect factors 5 and 10a and thrombin?

Answer 10

Thrombin acts to potentiate factors 8 and 9 (APTT) and so therefore it is most sensitive for the monitoring of heparin

Question 11

What are the complications of heparin?

Answer 11

Bleeding
Heparin induced thrombocytopenia (with thrombosis) - monitor FBC in patients on heparin
Osteoporosis with long term use; increases osteoclast activity

Question 12

How can heparin be reveresed?

Answer 12

Stop (half life of unfractionated heparin is half a min)

Severe; protamine sulphate to reverse antithrombin effect

Question 13

Will protamine sulphate completely reverse LMWH?

Answer 13

No; partially

Will completely reverse unfractionated heparin

Question 14

Describe vitamin K

Answer 14

Fat soluble vitamin
Absorbed upper intestine
Requires bile salts
Final carboxylation; 2,7,9,10

Question 15

How does vitamin K result in carboxylation of clotting factors?

Answer 15

Adds 1 of the 2 COOH groups essential for coagulation factor to bind to calcium on the platelet membrane
Without the second COOH group, the chemical bond is too weak for effective attachment resulting in failure of coagulation cascade

Question 16

How can warfarin be initiated?

Answer 16

Rapid (cute event) or slow (AF, liver failure, malnourished, elderly)
Stabilise INR between 2-3
Maintain INR; dose taken at same time every day
NARROW THERAPEUTIC WINDOW - metabolised by cytochrome p450

Question 17

What is the INR?

Answer 17

Mathematical correction that normalises PT ratio by adjusting for variability in the sensitivity of different thromboplastins

Question 18

What isthe major adverse effects of warfarin?

Answer 18

Haemorrhage

Question 19

What can increase the risk of bleeding on warfarin?

Answer 19

Intensity of anticoagulation; INR
Concomitant clinical disorders
Use of other medications; drug-drug interaction
Quality of management

Question 20

What are mild bleeding complications?

Answer 20

Skin bruising
Epistaxis
Haematuria - this requires investigation

Question 21

What are severe bleeding complications?

Answer 21

GI
Intracerebral
Significant drop in Hb

Question 22

How can warfarin be reversed?

Answer 22

Omit warfarin dose
Administer oral vitamin K
Administer prothrombin complex
Aim for INR <5.0

Question 23

What is the speed of action of the reveresal mechanisms of warfarin?

Answer 23

Vit K - 6 hours
Clotting factors (prothrombin complex) - immediate

Question 24

What is an examples of a direct thrombin inibitor?

Answer 24

Dabigatran

Question 25

What is an examples of a direct 10a inhibitor?

Answer 25

Edoxaban
Rivaroxaban
Apixaban

Question 26

What are the new anticoagulants used for?

Answer 26

Replacement of LMWH as prophylaxis in elective hip and knee replacement
Treatment of DVT/ PE
Stroke prevention in AF

Question 27

In what conditions is warfarin still indicated?

Answer 27

Metal heart valves

APS

Question 28

What is the duration of anticoagulation in DVT/ PE?

Answer 28

First episodes of DVT/ PE require at least 3 months of anticoagulation
Consider extending to 6 months in patients with more extensive, life-threatening clot presentation, transient risk factors or evidence of a persistent clot at 3 months

Question 29

What is the management of an INR of 5-8 with no bleeding?

Answer 29

Withhold 1-2 doses

Restart warfarin at a lower maintenance dose once INR <5

Question 30

What is the management of an INR of 5-8 with minor bleeding?

Answer 30

Stop warfarin and admit for urgent IV vitamin K

Restart warfarin when INR < 5

Question 31

What is the management of an INR >8 with minor bleeding?

Answer 31

Stop warfarin and admit for urgent IV vitamin K
Check INR daily
Repeat vitamin K if INR too high after 24 hours
Restart warfarin at a lower dose when INR <5

Question 32

What is the management of a major bleed whilst on warfarin?

Answer 32

STOP
Give prothrombin complex 50 units/ kg
IV vitamin K