Anticoagulant Drugs

Question 1

when are anticoagulant drugs indicated?

Answer 1

Venous thrombosis – stasis is the risk factor (not platelet more fibrin)
Atrial fibrillation

Question 2

what are the naturally occurring anticoagulants in the body?

Answer 2

• Serine protease inhibitors (antithrombin)

* Protein C and Protein S

Question 3

what are the screening tests for fibrin clot formation?

Answer 3

• APTT – activated partial thromboplastin time (for heparin)

* PT – Prothrombin time (for warfarin)

Question 4

how does heparin work?

Answer 4

• Potentiates antithrombin
• Immediate effect
• Parenteral (iv or sc)

Question 5

what are the 2 forms of heparin?

Answer 5

o	Unfractionated (binds to antithrombin stabilizes it and helps its effect)
o	low molecular weight (LMWH) (predominantly antithrombin anti Xa interaction)

Question 6

how should heparin be monitored?

Answer 6

o Activated partial thromboplastin time (APTT) for unfractionated
o Anti-Xa assay for LMWH but usually no monitoring of LMWH is required as more predictable response

Question 7

what are the potential complications of heparin?

Answer 7

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

Question 8

how is heparin reversed?

Answer 8

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

Question 9

what role does vitamin K have in coagulation?

Answer 9

Final carboxylation of clotting factors II, VII, IX and X
Synthesised in liver
Require vitamin K for final carboxylation step essential for function
o Carboxylation of glutamic acid residues in factors
o II, VII, IX and X (as well as Protein C and S).

Question 10

how does warfarin work?

Answer 10

inhibits vitamin K

By antagonising Vitamin K in the liver there is synthesis of non-functional coagulation factors

Question 11

steps of warfarin introduction?

Answer 11

Initiation - Rapid or Slow
Stabilisation
Maintenance – dose should be taken at same time every day (6pm recommended)
Initially can increase coagulation risk so given with heparin always at start

Question 12

how is warfarin monitored?

Answer 12

INR - international normalized ratio
o INR is a mathematical correction of PT ratio for differences in the sensitivity of thromboplastin reagents
o Allows for comparison of results between labs and standardizes reporting of PT

Question 13

what factors influence bleeding on warfarin?

Answer 13

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

Question 14

what are the potential bleeding complications in warfarin?

Answer 14

Mild
Skin bruising
Epistaxis
Haematuria

Severe
Gastro-intestinal
Intracerebral
Significant drop in Hb

Question 15

how is warfarin reduced?

Answer 15

o Omit warfarin doses
o Administer oral vit K
o Administer clotting factors (factor concentrates)
o Clinical and laboratory assessment of response

Question 16

how is acute bleeding as a result of warfarin managed?

Answer 16

Depends on the severity of bleeding and INR
Speed of action
- Vitamin K – 6 hours
- Clotting factors – immediate

Question 17

name a direct thrombin inhibitor?

Answer 17

dabigatran

Question 18

name 3 direct activated factor X inhibitors

Answer 18

edoxaban
rivaroxaban
apixaban

Question 19

what are the advantages of new anticoagulants (direct activated X inhibitors)

Answer 19

o Oral and no monitoring required
o Less drug interactions
o Recently developed specific antidotes for reversal

Question 20

when are new anticoagulants used?

Answer 20

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