Anticoagulants and Thrombolytics Flashcards
What are the three contributors to thrombolytic disease according to Virchow’s triad?
Hypercoagulability
Endothelial damage
Stasis
How does Warfarin work?
Inhibits the production of Vitamin K dependent clotting factors (II, VII, IX, X)
2 7 9 10
Warfarin has a _____ onset of action
What does this mean clinically?
Slow
Give Heparin to cover initially and give a loaded dose to start (10mg)
Warfarin has a _____ half life
What does this mean clinically?
Long (48 hours)
Sould be stopped 3 days before surgery
If a female patient is on Warfarin, why do we need to advise her re:pregnancy?
It crosses the placenta
Tratogenic in 1st trimester
Can cause brain haemorrhage in 3rd trimester
How can we monitor therapeutic dose of Warfarin in patients?
PTT
INR
GIve examples of 3 clinically significant drug types that potentiate the effects of Warfarin
- Drugs inhibiting hepatic metabolism
- Amiodarone, Quinolone, alcohol - Drugs inhibiting platelet function
- Aspirin - Drugs reducing vitamin K from gut bacteria
- Cephalosporin abx
GIve examples of 3 clinically significant drugs that reduce the effects of Warfarin
Antiepileptics
Rifampicin
St Johns Wort
What are the indications for the use of Warfarin?
What are the target INR ranges for these patients?
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
List some adverse effects of Warfarin
Bruising
Bleeding- intracranial, GI, wounds
Teratogenic effects
What methods can be used to reverse the effects of Warfarin?
Parenteral vitamin K - slow
Prothrombin complex comcentrate
Fresh frozen plasma - fast
What kind of things might you want to discuss with a patient when starting them on Warfarin?
Side effects- bleeding, bruising
Pregnancy advice
Other medications including OTC drugs
Alcohol use
INR monitoring
What special property of heparins allow them to bind proteins effectively and elict their effects?
Highly negatively charged
(highest of all things known)
How do heparins elict their anti-coagulative effects?
Activation of anti-thrombin
Deactivating factor Xa and IIa
What are the two broad types of heparin that are used clinically?
Unfractionated Heparin (20kDa)
Low Molecular Weight Heparin (3-4kDa)
How are the different types of heparin administered?
Unfractionated Heparin: IV or subcut. for prophylaxis
LMW Heparin: Subcut.
In order to catalyse the inhibition of IIa and AT III, heparin needs to bind simultaneously to ____ and _______.
Are all Heparins capable of this?
Factor IIa and Antithrombin III
No, only unfractionated Heparin is big enough to bind both
Unlike unfractionated heparin, LMW Heparin is a poor direct inactivator of _______.
Thrombin (IIa)
How does the dosing and monitoring of LMW heparin compare with that of unfractionated Heparin?
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
LMW heparins are less likely than unfractionated heparin to cause what complication?
Thrombocytopenia
What is the difference between the dose-response curve of unfractionated heparin compared to LMW heparin?
UF heparin: non-linear
LMW heparin: predictable
LMW heparin is used clinically in which circumstances?
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
List some of the adverse effects of heparin
Brusing/bleeding- intracranial, GI, epistaxis
Thrombocytopenia (loss of platelets–>thrombosis)
In cases of thrombocytopenia caused by heparin, what action should be taken?
Stop heparin
Start hirudin
What agent can be used to reverse the action of heparin?
How does it achieve this?
Protamine sulphate
Dissociates heparin from anti-thrombin III, irreversibly binds heparin
If you wish to reverse heparin therapy, what steps should you take?
Stop heparin
If actively bleeding: give protamine
Give some examples of anti-platelet drugs and their mechanism of action
Aspirin: COX-1 inhibitor
Dipyridamole: Phosphodiesterase inhibitor (increases cAMP)
Clopidogrel: ADP antagonist
Abciximab: Glycoprotein IIb/IIIa inhibitor
