Anticoagulant Drugs

Question 1

What are some indications for anticoagulant drugs?

Answer 1

Venous thrombosis

AF

Question 2

What do anticoagulant drugs target?

Answer 2

The formation of the fibrin clot

Question 3

Describe heparin

Answer 3

Potentiates antithrombin
Immediate effect
Parenteral (IV or SC)
2 forms- unfractionated, low molecular weight (LMWH)

Question 4

Where do unfractionated and LMWH act?

Answer 4

Antithrombin III inhibition of Thrombin (more so unfractionated)
AT III inhibition of V/Xa (more so LMWH)

Question 5

How is unfractionated heparin monitored?

Answer 5

aPTT

Question 6

How is LMWH monitored?

Answer 6

Anti-Xa assay, but usually no monitoring required as predictable response

Question 7

What are some complications of heparin?

Answer 7

Bleeding
Heparin induced thrombocytopenia (with thrombosis) HITT - monitor FBC in patients on heparin
Osteoporosis with long term use

Question 8

How should heparin be reversed?

Answer 8

Stop heparin (short t1/2)
Occasionally in severe bleeding-
Protamine sulphate
Reverses antithrombin effect
Complete reversal for unfractionated
Partial reversal for LMWH

Question 9

What are the coumarin anticoagulants?

Answer 9

Warfarin
Phenindione
Acenocoumarin
Phenprocoumon

Question 10

What is the mechanism of action of the coumarin anticoagulants?

Answer 10

Inhibition of Vit K

Question 11

Describe the Vit K Dependent factors

Answer 11

Factors II (prothrombin), VII, IX & X- Protein C and protein S
Synthesised in liver
Require vitamin K for final carboxylation step essential for function

Question 12

What is the action of Vit K?

Answer 12

Carboxylation of glutamic acid residues in factors

II, VII, IX and X (as well as Protein C and S)

Question 13

What is the mechanism of action of warfarin?

Answer 13

Blocks the ability of Vitamin K to carboxylate the Vitamin K dependent clotting factors, thereby reducing their coagulant activity

Question 14

Describe warfarin therapy

Answer 14

Initiation- rapid for acute thrombosis in hospital with heparin, slow for AF in community and for liver failure, malnourished, elderly etc
Narrow therapeutic window- therapy needs monitored
Stabilisation
Maintenance- dose same time every day (6pm recommended)

Question 15

What is the INR equation?

Answer 15

(Patients PT in secs/Mean Normal PT in secs) ^ISI (International Sensitivity Index)

Question 16

What is the INR?

Answer 16

A mathematical “correction” (of the PT ratio) for differences in the sensitivity of thromboplastin reagents
Allows for comparison of results between labs and standardizes reporting of the prothrombin time

Question 17

What factors may influence bleeding risk in warfarin?

Answer 17

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

Question 18

What are some bleeding complications?

Answer 18

Mild- skin bruising, epistaxis, haematuria

Severe- GI, intracerebral, significant drop in Hb

Question 19

How is warfarin reversed?

Answer 19

No action
Omit Warfarin dose(s)
Administer oral Vitamin K
Administer clotting factors (FFP or factor concentrates)
Clinical and laboratory 
assessment of response

Question 20

How is bleeding managed?

Answer 20

Dependant on- Severity of bleeding, INR
Speed of action -
Vitamin K - 6 hours
Clotting factors - immediate

Question 21

What are some new anticoagulants?

Answer 21

Oral direct thrombin inhibitors- dabigatran
Oral Xa inhibitors- rivaroxaban, apixaban
No monitoring required, less drug interactions, no specific antidote for reversal currently

Question 22

What does warfarin have an effect on?

Answer 22

Prothrombin, VIIa, IXa and Xa

Question 23

When should new anticoagulants be used?

Answer 23

Used instead of LMWH as prophylaxis in elective hip and knee replacement surgery
Used for selected patients for stroke prevention in atrial fibrillation
Used for treatment of DVT/PE