Tuesday, August 7, 2018

Warfarin and Newer Oral Anticoagulants (NOACs) notes

Hey guys!
These are my notes from Harrison on Warfarin and Newer Oral Anticoagulants (NOACs).

Warfarin

MOA: Warfarin inhibits vitamin K epoxide reductase (VKOR), thereby blocking the γ-carboxylation process. This results in the synthesis of vitamin K–dependent clotting proteins that are only partially γ-carboxylated.

Dosing: Warfarin is usually started at a dose of 5–10 mg. The dose is then titrated to achieve the desired target INR.

Reversal:
Vitamin K
Fresh-frozen plasma as a source of the vitamin K–dependent clotting proteins
Four factor prothrombin complex concentrates (contains all four vitamin K–dependent clotting proteins)

Newer Oral Anticoaglants (NOACs)

MOA: Dabigatran targets thrombin
Rivaroxaban, apixaban, and edoxaban, target factor Xa

Dosing: For stroke prevention in patients with nonvalvular atrial fibrillation, rivaroxaban is given at a dose of 20 mg once daily with a dose reduction to 15 mg once daily in patients with a creatinine clearance of 15–49 mL/min; dabigatran is given at a dose of 150 mg twice daily with a dose reduction to 75 mg twice daily in those with a creatinine clearance of 15–30 mL/min; and apixaban is given at a dose of 5 mg twice daily with a dose reduction to 2.5 mg twice daily for patients with a creatinine > 1.5 g/dL, for those 80 years of age or older, or for patients who weigh < 60 kg

Reversal:
There are no specific antidotes for the new oral anticoagulants. (According to Harrison however I have updates...)
New updates:
Idarucizumab (pronounced "I-dare-you-cizumab") is a humanized anti-dabigatran monoclonal antibody fragment that can be used for emergency reversal of the anticoagulant effect of dabigatran.
Andexanet was approved by the US FDA in May of 2018 for the reversal of anticoagulation by rivaroxaban and apixaban in individuals with life-threatening or uncontrolled bleeding associated with these drugs.

Pros of NOACs: INR monitoring not required.
Alternative to warfarin for stroke prevention in nonvalvular atrial fibrillation.
PS: Nonvalvular atrial fibrillation is defined as that occurring in patients without mechanical heart valves or severe rheumatic valvular disease, particularly mitral stenosis and/or regurgitation.
Cons of NOACs: Can not be used for valvular atrial fibrillation.
No agents for reversal / agent for reversal is expensive.
Contraindicated in pregnancy.
Renal dosing.

That's all!
-IkaN

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