Week 2 part 3

Question 1

Indications for anticoagulant drugs

Answer 1

Venous thrombosis

Atrial fibrillation

Question 2

Heparin

Answer 2

Potentiates antithrombin
Immediate effect
Parenteral (iv or sc)
2 forms - unfractionated & LMWH

Question 3

Heparin mechanism of action

Answer 3

inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.

Question 4

Monitoring of heparin

Answer 4

Activated partial thromboplastin time (APTT) for unfractionated

Anti-Xa assay for LMWH but usually no monitoring of LMWH is required as more predictable response

Question 5

Heparin complications

Answer 5

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

Question 6

Heparin - reversal

Answer 6

Stop the heparin (short half-life)

Occasionally in severe bleeding -
Protamine sulphate - Reverses antithrombin effect: Complete reversal for unfractionated, Partial reversal for LMWH

Question 7

Coumarin anticoagulants examples

Answer 7

warfarin
phenindione
acenocoumarin
phenprocoumon

Question 8

Coumarin anticoagulants mechanism of action

Answer 8

inhibition of vitamin K

Question 9

Vitamin K

Answer 9

Fat soluble vitamin
Absorbed upper intestine
Requires bile salts for absorption
Final carboxylation of clotting factors II, VII, IX and X

Question 10

Action of Vitamin K

Answer 10

Carboxylation of glutamic acid residues in factors II, VII, IX and X (as well as Protein C and S).

Question 11

Warfarin mechanism of action

Answer 11

Inhibits epoxide reductase preventing the reduction of vitamin K to its active hydroquinone form

This in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X and protein C.

Question 12

What does INR stand for?

Answer 12

International Normalized Ratio

Question 13

INR Equation

Answer 13

INR = Patients PT in seconds / Mean normal PT in seconds

PT = Pro-thrombin time

Question 14

Warfarin: Major Adverse Effects

Answer 14

Haemorrhage

BEWARE DRUG INTERACTIONS

Question 15

What factors may increase warfarin bleeding (adverse effect)?

Answer 15

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

Question 16

Bleeding complications of warfarin

Answer 16

Mild = skin bruising, epistaxis, haematuria
Severe = gastro-intestinal, intracerebral, significant drop in Hb

Question 17

Reversal of warfarin

Answer 17

No action
Omit Warfarin dose(s)
Administer oral Vitamin K
Administer clotting factors (factor concentrates)

Question 18

Speed of action of Vitamin K and clotting factors in warfarin reversal

Answer 18

Vitamin K - 6 hours

Clotting factors - immediate

Question 19

Thrombin inhibitors examples

Answer 19

epirudin, desirudin, bivalirudin and argatroban, dabigatran

Question 20

Dabigatran adverse effects (direct thrombin inhibitor)

Answer 20

Unsurprisingly haemorrhage is the major adverse effect.

Doses should be reduced in chronic kidney disease and dabigatran should not be prescribed if the creatinine clearance is < 30 ml/min.

Question 21

Xa inhibitors examples

Answer 21

Edoxaban, Rivaroxaban, Apixaban

Remember Xa converts prothrombin to thrombin

Question 22

Reversal of dabigatran

Answer 22

Idarucizumab cab be used for rapid reversal of the anticoagulant effects of dabigatran.

Question 23

Reversal of Edoxaban, Rivaroxaban, Apixaban (direct factor Xa inhibitors)

Answer 23

Andexanet alfa

Question 24

Aspirin mechanism of action

Answer 24

Anti-platelet drug
Inhibits cyclo-oxygenase which is necessary to produce Thromboxane A2 (a platelet agonist released from granules on activation).

Question 25

Aspirin side effects

Answer 25

1. Bleeding
2. Blocks production of prostaglandins:
   GI ulceration
3. Bronchospasm

Question 26

ADP receptor antagonists examples

Answer 26

Clopidogrel, prasugrel

Anti-platelet drugs

Question 27

Dipyridamole

Answer 27

Phosphodiesterase inhibitor - increases production of cAMP which inhibits platelet aggregation.
(Anti-platelet drug)

Question 28

GP IIb/IIIa inhibitors

Answer 28

eg abciximab - inhibit aggregation

Platelets attach to each other via GPIIbIIIa and fibrinogen

Question 29

Reversal of bleeding caused by anti-platelet drugs

Answer 29

Anti-platelet drugs tend to affect platelet function for their 7-10 day life span

Stop anti-platelet agents 7 days prior to elective operations

If serious bleeding - can reverse with platelet transfusion