Reversal of Dabigatran
The incredible folks from hqmeded have put up a video on how to deal with bleeding patients on the new oral anticoagulant, dabigatran…
Here is the Hennepin County Reversal Protocol from the Video
What I took from this excellent resource:
- Thrombin Time is probably the best available way to monitor this drug, but due to lack of lab standardization, we cannot establish non-institutional ranges
- If aPTT is totally normal (<1.5x), unlikely that sig. drug effect is present
- Can be dialyzed and ~60% will be removed at 2-3 hour mark
- Despite the rec that FFP or PCC may be helpful, I am not sure why this would be the case. Factor VIIa or FEIBA seems the best choices, albeit not great or proven ones. I could totally be talking out of my arse, though.
- Activated charcoal will adsorb this drug if the patient took it <2 hours ago.
Here is a great review article on dabi.
The blog Clot Connect MD put up these references:
References
- van Ryn J. Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116–1127.
- Crowther MA. Managing bleeding in anticoagulated patients with a focus on novel therapeutic agents. J Thromb Haemost 2009; 7 (Suppl 1):107–110.
- Eerenberg ES et al. Prothrombin Complex Concentrate reverses the anticoagulant effect of Rivaroxaban in healthy volunteers (abstract 1094; ASH annual meeting Dec 4-7, 2010, Orlando, FL).
- Morishima Y et al. Anti-Inhibitor Coagulant Complex, Prothrombin Complex Concentrate, and recombinant factor VIIa reverse prothrombin time prolonged by Edoxaban in human plasma (abstract 3319; ASH annual meeting Dec 4-7, 2010, Orlando, FL)
and linked to another reversal protocol from UNC
great post from EM Lit of Note, pointing to a study that PCCs will reverse Rivaroxaban, but Not Dabigatran (these were non-activated PCCs AFAIK)
“Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate.” www.ncbi.nlm.nih.gov/pubmed/21900088
Leon Gussow of the Poison Review has another excellent post on the top 10 questions on Dabigatran
Just published study indicates that Dabi may not cause enlarged hematomas in head bleeds (Circulation 2011;124:1654-1662)
For a better understanding (if you are smarter than me) of how Dabigatran Etexilate affects lab assays, see this article Thromb Haemostasis 2012;107(5) Douxfils et al.)
New article confirms a normal PTT and INR means no sig. dabigatran on board (PMID:23232017)
Letter to editor stating aPCC reverses dabi (British Journal of Haematology, 2013, 164, 296–310)
Exvivo study on human blood shows PCC and aPCC can reverse dabi (Critical Care 2014, 18:R27 )
Antidote seems to work: N Engl J Med 2015; 373:511-520 DOI: 10.1056/NEJMoa1502000
Dialysis works, but there may be rebound [cite source='doi']10.1111/jth.13117[/cite]
Professor
Nassau University Medical Center
No conflicts of interest (coi).
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hope all is well this early summer. Curious if the patient gets hemodialysis w/o heparin if the patient has a head bleed? TT time means the same as prothrombin time as an assay? factor 7 versus PCC, unknown which is better. I am not sure why the FDA would approve such a drug w/o a clear antidote. I guess the next product on market would be recombinant Thrombin to give to patients.
Jose,
great question. have not seen data, but i believe he the dabi itself should be enough anti-coag for the HD. When the filter clots, you are probably ready to stop the dialysis. TT is different than PT, unfortunately, so regular coags prob not the way to go. If it was my head I would want the Factor VIIa, b/c I really don’t see why PCC would do anything. As to FDA, you could argue that ther. dabi may still be a better deal than the frequent head bleeds we see with crazy INRs in pts on warfarin.
Hi,
Would you mind explaining your reasoning that Factor VIIa would be superior to PCC in this case?
My thoughts are (with the proviso, that i have no good evidence for any of this) that 3-factor PCC brings very little tot he table. None of these factors are in shortage with dabi and not sure how much thrombin for direct comptetition with dabi is going to be generated. 4-factor seems ok, b/c at least you have the VIIa, but why not just give the VIIa then in greater concentrations. This will get you the TF thrombin burst, which is probably where the money is. Also, putatively you are going to get direct plt activation with the VIIa preps.… Read more »
FEIBA should work, however
Scott,
Are you saying FEIBA should be better b/c it contains VIIa? And when you mention 4 factor PCC in the above comment isn’t that the same as FEIBA? Thanks for your help and clarification.
FEIBA is four factor with ACTIVATED factor VII; other 4-factor have inactive factor VII.
FEIBA also has activated II (thrombin), which is why (activated) PCC should work better than VIIa.
dabigatran inhibits thrombin (even if fibrin-bound), so even if you feed the coag system proximal to inhibited-thrombin, there should not be as much of an effect
not a lot of clinical data out there, though
(also, activated 3-factor pcc should work too)
VIIa has a signficant risk of thrombosis – even 4-factor PCC has a higher risk of thrombosis than 3-factor PCC.
James, do you have anything to support the thrombin content of FEIBA. I am doubtful there is any significant amount of thrombin in the product. If infusion of thrombin actually worked, we can dispense with the rest of the clotting cascade. Unfortunately, thrombosis rates really can’t be compared between studies–the selection and baseline clotting rates differ between each of the studies and makes it tough to really assess which products have increased relative rates.
As a relatively new patient taking this drug (3/11), this is important information to me. I just hope that if I do need to go into the ER with a bleed, they won’t be depending on me to figure it all out. O_o I have to say that I am not missing the monthly (or more frequent) trips to the cardiologist’s office for INR tests. And also dealing with my INR spikes and lows occurring without any changes in diet, and preparing for a procedure, although a pacer in Feb. has fixed what has been ailing me. If my next… Read more »
It has been a year and a half since I first read this website and listened to the video. Has anyone come up with any new strategies based on experience and experimentation? Thanks.
there are none. the company will self-release a very expensive antibody antidote.
They should not release drugs like this until they modify it so that it’s effects can be reversed or inactivated. How did these drugs get past the ethics committee?