Trauma and Novel Oral Anticoagulants

There has been a dramatic uptick in the the use of Novel Oral Anticoagulants (NOAC).  In the last five years, there have been mutliple publications of efficacy and noninferiority trials comparining traditional vitamin K antagonists (VKA) and both direct thrombin inhibitors (DTI) and Factor Xa inhibitors (FXI) for the indication of CVA prevention in atrial fibrillation and treatment of VTE.

Anticoagulants, in general, pose an increased risk of morbidity and mortality in the setting of trauma.  VKAs have long been used and have a both an easily measured effect on readily available blood tests (PT/INR) and well-established and effective reversal agents exist.  

 

DTI and FXI are challenging because their effect can't be easily measured and can't be easily reversed.  For the next couple of paragraphs, each of the above classes will reviewed.

Factor Xa Inhibitors

The FXIs approved in the United States for use are rivaroxaban (Xarelto) and apixaban (Eliquis).  The half-life of these agents are each approximately 9 hours.  These agents have a trivial impact on a patient's coagulation panel with only mild elevation in PTT; thus, an obtunded patient unable to provide a meaningful history may be, for the care team, unknowingly on an one of these anticoagulants.

Traditional reversal with Vitamin K and FFP are ineffectual.  Successful reversal in a series of small trials using four factor activated prothrombin complex concentrates (aPCC, factors II, VII, IX, and X) has thus influenced reversal protocols at many institutions.  aPCC as currently available in the United States are of the three factor variety (factors II, IX, and X, eg FEIBA and Autoplex T) and are easy to use, small volume, but generally expensive and not as of yet proven.

 

One additional option not commonly employed during trauma with massive hemorrhage is the use of charcoal to reduce absorption of these NOACs.  This applies to both FXIs as discussed above and DTIs as to be discussed next.

 

Direct Thrombin Inhibitor

 

The only currently approved DTI in the United States for VTE and CVA prevention is dabigitran (Pradaxa) with a half-life of approximately 14 hours.  Similar to FXIs, alteration of standard coagulation panels are trivial except mild elevations in PTT.  DTIs can also lead to very trivial increases in PT/INR (INRs around 1.2).  What can be used to monitor DTIs?  Well, one option is ecarin thrombin time (ECT), which measures thrombin generation and does function as a way to measure a 'level' for this medication.  This test, however, is not readily available at most hospitals as of yet.

 

Reversal of dabigitran is even more troublesome than VKAs and FXIs because FFP, Vitamin K and aPCC are all more or less useless.  Because dabigitran is renally excreted and not protein bound, hemodialysis is really the only proven option for reversal.  HD only eliminates about 65% of dabigitran.

In summary, NOACs are having a significant increase in market penetration as treatment for VTE and CVA prevention in atrial fibrillation.  These agents do not require a bridge, do not require monitoring (PT/INR checks), and have a predictable effect, not altered by dietary changes nor significant interactions with medications as seen in VKAs.

 

From a trauma standpoint, these novel agents are rife with concern.  No antidote exists for either DTIs or FXIs.  AND, these agents are difficult to detect and challenging to monitor the success of attempted reversal with aPCCs.  Each institution ought to have a protocol and if one does not exist, then Emergency Physicians, Surgeons, and Hematologists should sit down and hammer one out.

 

References

Bruins Slot K, Berge EFactor Xa Inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation. Cochrane review, 2013.

Eerenberg et al.  Reversal of rivaroxaban and dabigatran by Prothrombin complex concentrate.  Circulation 124, 2011.

 

Hillarp A et al.  Effects of oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays.  J Thromb Haemost, 9, 2011.

 

Lindahl T et al.  Effects of oral, direct thrombin inhibitor dabigatran on five common coagulation assays.  J Throm Haemost, 105, 2011.

 

Miyares M, Davis K.  Newer Anticoagulants: A review of laboratory monitoring options and reversal agents in the hemorrhagic patient.  Am J Health-Syst Pharm, 69, 2012 (available online at http://www.ashp.org/DocLibrary/AJHP/Newer-oral-anticoagulants.aspx )

 

submitted by Dr. Charles Pearce