Anticoagulants and Thrombolytics

Question 1

What are the three contributors to thrombolytic disease according to Virchow’s triad?

Answer 1

Hypercoagulability

Endothelial damage

Stasis

Question 2

How does Warfarin work?

Answer 2

Inhibits the production of Vitamin K dependent clotting factors (II, VII, IX, X)

2 7 9 10

Question 3

Warfarin has a _____ onset of action

What does this mean clinically?

Answer 3

Slow

Give Heparin to cover initially and give a loaded dose to start (10mg)

Question 4

Warfarin has a _____ half life

What does this mean clinically?

Answer 4

Long (48 hours)

Sould be stopped 3 days before surgery

Question 5

If a female patient is on Warfarin, why do we need to advise her re:pregnancy?

Answer 5

It crosses the placenta

Tratogenic in 1st trimester

Can cause brain haemorrhage in 3rd trimester

Question 6

How can we monitor therapeutic dose of Warfarin in patients?

Answer 6

PTT

INR

Question 7

GIve examples of 3 clinically significant drug types that potentiate the effects of Warfarin

Answer 7

1. Drugs inhibiting hepatic metabolism
   - Amiodarone, Quinolone, alcohol
2. Drugs inhibiting platelet function
   - Aspirin
3. Drugs reducing vitamin K from gut bacteria
   - Cephalosporin abx

Question 8

GIve examples of 3 clinically significant drugs that reduce the effects of Warfarin

Answer 8

Antiepileptics

Rifampicin

St Johns Wort

Question 9

What are the indications for the use of Warfarin?

What are the target INR ranges for these patients?

Answer 9

DVT (3-6 months) : Target 2.0-3.0

PE (6 months): Target 2.0-3.0

AF (until risk>benefit): Target 2.0-3.0

Mechanical prosthetic valves (high risk): Target 2.5-4.5

Recurrent thrombosis on Warfarin: Target 2.5-4.5

Thrombosis assocatied with inherited thrombophilia conditions: Target 2.5-4.5

Question 10

List some adverse effects of Warfarin

Answer 10

Bruising

Bleeding- intracranial, GI, wounds

Teratogenic effects

Question 11

What methods can be used to reverse the effects of Warfarin?

Answer 11

Parenteral vitamin K - slow

Prothrombin complex comcentrate

Fresh frozen plasma - fast

Question 12

What kind of things might you want to discuss with a patient when starting them on Warfarin?

Answer 12

Side effects- bleeding, bruising

Pregnancy advice

Other medications including OTC drugs

Alcohol use

INR monitoring

Question 13

What special property of heparins allow them to bind proteins effectively and elict their effects?

Answer 13

Highly negatively charged

(highest of all things known)

Question 14

How do heparins elict their anti-coagulative effects?

Answer 14

Activation of anti-thrombin

Deactivating factor Xa and IIa

Question 15

What are the two broad types of heparin that are used clinically?

Answer 15

Unfractionated Heparin (20kDa)

Low Molecular Weight Heparin (3-4kDa)

Question 16

How are the different types of heparin administered?

Answer 16

Unfractionated Heparin: IV or subcut. for prophylaxis

LMW Heparin: Subcut.

Question 17

In order to catalyse the inhibition of IIa and AT III, heparin needs to bind simultaneously to ____ and _______.

Are all Heparins capable of this?

Answer 17

Factor IIa and Antithrombin III

No, only unfractionated Heparin is big enough to bind both

Question 18

Unlike unfractionated heparin, LMW Heparin is a poor direct inactivator of _______.

Answer 18

Thrombin (IIa)

Question 19

How does the dosing and monitoring of LMW heparin compare with that of unfractionated Heparin?

Answer 19

LMW heparin requires less frequent dosing as it has a biologically long half life

Doesn’t require the same monitoring as it affects Factor Xa specifically

Question 20

LMW heparins are less likely than unfractionated heparin to cause what complication?

Answer 20

Thrombocytopenia

Question 21

What is the difference between the dose-response curve of unfractionated heparin compared to LMW heparin?

Answer 21

UF heparin: non-linear

LMW heparin: predictable

Question 22

LMW heparin is used clinically in which circumstances?

Answer 22

Prevention of thrombo-embolism peri-operatively or in immobile individuals

Treatment of DVT/PE and AF (until loading dose of warfarin is achieved) Treatment of acute coronary syndromes

In pregnancy- CAUTIOUSLY and in place of of warfarin

Question 23

List some of the adverse effects of heparin

Answer 23

Brusing/bleeding- intracranial, GI, epistaxis

Thrombocytopenia (loss of platelets–>thrombosis)

Question 24

In cases of thrombocytopenia caused by heparin, what action should be taken?

Answer 24

Stop heparin

Start hirudin

Question 25

What agent can be used to reverse the action of heparin?

How does it achieve this?

Answer 25

Protamine sulphate

Dissociates heparin from anti-thrombin III, irreversibly binds heparin

Question 26

If you wish to reverse heparin therapy, what steps should you take?

Answer 26

Stop heparin

If actively bleeding: give protamine

Question 27

Give some examples of anti-platelet drugs and their mechanism of action

Answer 27

Aspirin: COX-1 inhibitor

Dipyridamole: Phosphodiesterase inhibitor (increases cAMP)

Clopidogrel: ADP antagonist

Abciximab: Glycoprotein IIb/IIIa inhibitor