Anticoagulants Carey Lecture Flashcards
What are the categories of antithrombotics?
- Anticoagulants
- Fibrinolytics
- Antiplatelets
What do anticoagulants do?
Stop clot formation and extension
What do fibrinolytics do (in general)?
Break up existing clots
What do antiplatelets do?
Decrease platelet activation and aggregation
What are the two types of thrombi and how do they differ?
- White thrombus (platelet rich, forms in arteries, MI)
- Red thrombus (fibrin/RBC rich, forms in veints, DVT/PE)
What does TXA2 do?
Vasoconstriction
What does vWF do?
Binds to exposed collagen fibers at the injured vessel surface
What does fibrinogen do?
- Forms bridges between adjacent platelets
- This results in an aggregate of platelets at the vessel injury site
What does thrombin (factor IIa) do?
Converts fibrinogen to fibrin (which forms the stable clot)
What is the final result of the coagulation cascade?
Fibrin threads create a plug to make a stable clot
What are the overall steps of platelet activation?
- Injury
- Collagen and vWF exposed
- Platelet adherence and activation
- Binding of fibrinogen
- Aggregation and plug formation
What are the mediators of platelet aggregation?
TXA2
ADP
5-HT
What are the pathways of the coagulation cascade and how are they activated?
- Intrinsic (activated by exposed endothelium)
- Extrinsic (activated by tissue damage)
- Common (intrinsic and extrinsic merge together)
What is the first step in the common pathway of coagulation?
Activation of Factor Xa
What is the last step in the intrinsic and extrinsic pathways of coagulation?
Activation of Factor Xa
What factors are necessary to form a clot?
Factor 2 (prothrombin) Factor 10
What does Factor Xa do in the coagulation cascade?
Combines with Factor 2 (prothrombin) to form thrombin
What factors are targeted by Warfarin?
SNOT
Seven, Nine, Ten (0), Two
What does prothrombin time (PT) measure?
Activity of Factors 2, 7, 9, 10
What is INR?
- International Normalized Ratio
- Same as PT but standardized worldwide
What does PTT measure?
Activity of Factors 2, 5, 7, 9, 10, 11, 12
What is activated clotting time (ACT)?
- Same as PTT but used in invasive/operating procedures
- Quicker result turnaround
What are the indirect thrombin inhibitors?
Heparin
LMWH (Enoxaparin)
Fondaparinux
How do indirect thrombin inhibitors act as anticoagulants?
Help antithrombin deactivate clotting factors
Heparin inhibits which clotting factors?
X and II
What is HIT?
- Heparin Induced Thrombocytopenia
- Antibody mediated adverse effect of heparin
- Strong a/w thrombosis
What are signs of HIT?
- Platelets fall more than 50% from baseline with nadir 20,000+
- Platelets start to fall on day 5-10 of therapy
- Thrombosis occurs while on heparin
- R/o other causes of thrombocytopenia
What is the treatment of HIT?
- Stop heparin, treat with IV direct thrombin inhibitor
- Do NOT give platelets
- Do NOT give warfarin until platelets return to normal
LMWH (enoxaparin) inhibits which factors?
Factors Xa, IIa
When should enoxaparin dose be reduced? When should it be stopped?
- Reduced in CrCl 20-30 ml/min
- Stopped in CrCl less than 20
What is fondaparinux and what does it do?
- Synthetic pentasaccharide
- Inhibits factor Xa via antithrombin
When should dose of fondaparinux be reduced? When should it be stopped?
- Reduced if CrCl less than 50
- Stopped if CrCl less than 30
How are indirect thrombin inhibitors reversed?
- Discontinue drug
- Give protamine sulfate by IV
- Fondaparinux has NO reversal agent!
What are the direct Xa inhibitors?
- Rivaroxaban
- Apixaban
- Edoxaban
When should rivaroxaban dose be reduced? When should it be stopped?
- Reduced if CrCl 15-50 (AF)
- Stopped if CrCl less than 30 (VTE)
- Do NOT use in severe hepatic dysfunction
When should apixaban NOT be used?
Severe hepatic and renal dysfunction
When should edoxaban be reduced? When should it be stopped?
- Reduce if CrCl less than 50
- Stop if CrCl less than 15, greater than 95
- Do NOT use in moderate or severe hepatic dysfunction
What are the direct thrombin inhibitors and which route are they given?
- Bivalirudin (IV)
- Argatroban (IV)
- Dabigatran (oral)
How do direct thrombin inhibitors and antithrombin interact?
DTIs act independent of antithrombin
When should bivalirudin dose be reduced?
- CrCl less than 30
- Hemodialysis
When should dabigatran be reduced? Stopped?
- Reduce if CrCl 15-30 (AF)
- Stop if CrCl less than 15 (AF) or less than 30 (VTE)
What does warfarin inhibit?
- Factors 2, 7, 9, 10
- Proteins C and S
How should warfarin be dosed initially?
- Start low
- 5 mg daily
When should warfarin be started at 2.5 mg daily?
- 75+ yo
- Hepatic insufficiency
- Critically ill
If INR is less than goal two times, how should warfarin dose be adjusted?
Increase WEEKLY dose 10-20%
If INR is higher than goal two times, how should warfarin dose be adjusted?
Decrease WEEKLY dose 10-20%
When should INR goal be 2.5 to 3.5?
- Mechanical mitral valve
- Any mechanical valve with risk factors (AF, HF, MI, embolism)
- Pts with predisposition for clotting who had a clotting event when INR was at 2-3
What are examples of drugs that interact with warfarin to increase INR?
- Amiodarone
- Bactrim
- Cipro
- Metronidazole
What are examples of drugs that interact with warfarin to decrease INR?
- Cigs
- Rifampin
- St. John’s wort
When warfarin is stopped, how long does it take to return to baseline? How about if Vit K is given?
About 5 days
about 1 day with Vit K
How should Vit K be given to reverse warfarin?
- Oral route is preferred (better absorption)
- Do NOT use SC or IM (erratic absorption)
How should IV Vit K be administered?
- 10 mg always diluted with 50 mL NS
- Administer over 10-30 mins
Which anticoagulants have CYP interactions?
Rivaroxaban and apixaban
*Warfarin
Which anticoagulants have P glycoprotein interactions?
- Rivaroxaban
- Apixaban
- Edoxaban
- Dabigatran
Which anticoagulants have reversal agents?
- Warfarin (Vit K)
- Heparin (Protamine)
- LMWH (Protamine)
Which anticoagulant is not good to use in poor OR excellent kidney function?
Edoxaban
