The clotting cascade was one of the first doodles posted on Sketchy Medicine, I’ve now updated it to include some of the Novel Oral Anticoagulants (NOACs): Dabigatran, Rivaroxaban and Apixiban.
Dabigatran (Pradaxa)
- Selective, reversible direct thrombin inhibitor
- Is actually a prodrug that reaches peak concentration 2-3 h post ingestion
- Approved (in Canada) for: Thromboprophylaxis in atrial fib, post-op, and treatment of VTE and VTE recurrence
- T1/2: 7-17 h
- CYP independent (not as many drug-drug interactions)
- Excreted in urine 95% / Feces 5%
- Reversal: hemodialysis?
- Big trial = RELY, REMEDY
Rivaroxaban (Xarelto)
- Selective, reversible direct factor Xa inhibitor
- Approved (in Canada) for: Thromboprophylaxis in atrial fib, post-op, and treatment of VTE and VTE recurrence
- T1/2: 3-9 h (relatively speedy!)
- CYP3A4
- Very good oral bioavailability
- Almost all of it is protein-bound in the serum
- Urine 70% / Feces 30%
- Reversal: ???? (not hemodialysis)
Apixaban (Eliquis)
- Selective, reversible direct factor Xa inhibitor
- Approved (in Canada) for: Thromboprophylaxis in atrial fib, post-op, and treatment of VTE and VTE recurrence (only atrial fib in the USA)
- T1/2: 8-15
- CYP3A4
- Almost all (95%) protein-bound in the serum
- Urine 30% / Feces 70%
- Reversal: ???? (not hemodialysis)
Reversal agents:
- Hemodialysis
- Only good for agents that aren’t highly protein bound (i.e. dabigatran).
- Warfarin, rivaroxaban and apixaban are all mostly bound to protein in the serum, so dialysis won’t get rid of them
- PCC
- Plasma-derived product containing factors II, IX and X (3-factor PCC) or II, VII, IX and X (4-factor PCC) in addition to variable amounts of proteins C and S, and heparin
- aPCC
- Plasma-derived product containing activated factors II, VII, IX and X
- Recombinant factor VIIa
- Looks good in test tubes, clinical evidence lacking
- Idarucizumab
- Humanized monoclonal antibody against dabigatran
- Andxanet alfa
- Recombinant factor Xa derivative
- Could theoretically be used for rivaroxaban and apixaban
Anticoagulation Assays
(Adapted from Jackson II & Becker, 2014)
Approach to bleeding
(From Siegal, 2015)
References
- Jackson II LR & Becker RC. (2014). Novel oral anticoagulants: pharmacology, coagulation measures, and considerations for reversal. Journal of Thrombosis and Thrombolysis, 37(3), 380-391.
- Ufer M. (2010). Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thrombosis and Haemostasis. 103: 572-585.
- Siegal DM. (2015). Managing target-specific oral anticoagulant associated bleeding including an update on pharmacological reversal agents. Journal of Thrombosis and Thrombolysis, 1-8.