Anticoagulant Drugs Flashcards
What are indications for anticoagulant drugs?
Venous thrombosis
AF
Why in an acute situation (DVT/ PE) must heparin be started alongside warfarin?
In the initial phases (2-3 days) of warfarin treatment levels of protein C and S will drop as they are also vitamin K dependent producing a prothrombotic state
Heparin acts instantly as an anticoagulant
What is the mechanism of heparin?
Potentiates antithrombin
What are the different forms of heparin?
Unfractionated; IV
LMWH; S/c
Do anticoagulants dissolve clots?
No; they prevent them from getting bigger and will stabilize the clot
What is the difference between unfractionated and LMWH heparin?
Unfractionated; binds to antithrombin - thrombin complex to stabilize it
LMWH; binds to antithrombin -10a complex to stabilise it
Does heparin require monitoring?
Yes; only unfractionated
Monitor APTT
LMWH heparin does NOT require monitoring (but in pregnant women if required, can do assay of factor 10a)
Why will IV unfractionated heparin be used over LMWH?
Renal failure
Can be stopped in event of bleeding, whereas LMWH will take around 6 hours to stop
What is the difference in monitoring of warfarin and unfractionated heparin?
Prothrombin time (INR) = warfarin APTT = unfractionated heparin
Why is APTT sensitive for heparin if it will affect factors 5 and 10a and thrombin?
Thrombin acts to potentiate factors 8 and 9 (APTT) and so therefore it is most sensitive for the monitoring of heparin
What are the complications of heparin?
Bleeding
Heparin induced thrombocytopenia (with thrombosis) - monitor FBC in patients on heparin
Osteoporosis with long term use; increases osteoclast activity
How can heparin be reveresed?
Stop (half life of unfractionated heparin is half a min)
Severe; protamine sulphate to reverse antithrombin effect
Will protamine sulphate completely reverse LMWH?
No; partially
Will completely reverse unfractionated heparin
Describe vitamin K
Fat soluble vitamin
Absorbed upper intestine
Requires bile salts
Final carboxylation; 2,7,9,10
How does vitamin K result in carboxylation of clotting factors?
Adds 1 of the 2 COOH groups essential for coagulation factor to bind to calcium on the platelet membrane
Without the second COOH group, the chemical bond is too weak for effective attachment resulting in failure of coagulation cascade
How can warfarin be initiated?
Rapid (cute event) or slow (AF, liver failure, malnourished, elderly)
Stabilise INR between 2-3
Maintain INR; dose taken at same time every day
NARROW THERAPEUTIC WINDOW - metabolised by cytochrome p450
What is the INR?
Mathematical correction that normalises PT ratio by adjusting for variability in the sensitivity of different thromboplastins
What isthe major adverse effects of warfarin?
Haemorrhage
What can increase the risk of bleeding on warfarin?
Intensity of anticoagulation; INR
Concomitant clinical disorders
Use of other medications; drug-drug interaction
Quality of management
What are mild bleeding complications?
Skin bruising
Epistaxis
Haematuria - this requires investigation
What are severe bleeding complications?
GI
Intracerebral
Significant drop in Hb
How can warfarin be reversed?
Omit warfarin dose
Administer oral vitamin K
Administer prothrombin complex
Aim for INR <5.0
What is the speed of action of the reveresal mechanisms of warfarin?
Vit K - 6 hours Clotting factors (prothrombin complex) - immediate
What is an examples of a direct thrombin inibitor?
Dabigatran
What is an examples of a direct 10a inhibitor?
Edoxaban
Rivaroxaban
Apixaban
What are the new anticoagulants used for?
Replacement of LMWH as prophylaxis in elective hip and knee replacement
Treatment of DVT/ PE
Stroke prevention in AF
In what conditions is warfarin still indicated?
Metal heart valves
APS
What is the duration of anticoagulation in DVT/ PE?
First episodes of DVT/ PE require at least 3 months of anticoagulation
Consider extending to 6 months in patients with more extensive, life-threatening clot presentation, transient risk factors or evidence of a persistent clot at 3 months
What is the management of an INR of 5-8 with no bleeding?
Withhold 1-2 doses
Restart warfarin at a lower maintenance dose once INR <5
What is the management of an INR of 5-8 with minor bleeding?
Stop warfarin and admit for urgent IV vitamin K
Restart warfarin when INR < 5
What is the management of an INR >8 with minor bleeding?
Stop warfarin and admit for urgent IV vitamin K
Check INR daily
Repeat vitamin K if INR too high after 24 hours
Restart warfarin at a lower dose when INR <5
What is the management of a major bleed whilst on warfarin?
STOP
Give prothrombin complex 50 units/ kg
IV vitamin K
