Due to insufficient and occasionally conflicting evidence, the use of prothrombin complex concentrates (PCCs) for reversal of direct factor Xa inhibitors (eg, rivaroxaban, apixaban, and edoxaban) is NOT recommended.¹ This is because PCCs have no effect on the anti-Xa assay, the most accurate measure of anticoagulation for direct factor Xa inhibitors.

Although several in vitro and in vivo studies initially suggested that PCCs may be effective for this purpose, anti-Xa activity has not been measured in these studies^2-4; PT and aPTT are not reflective of the anticoagulation activity of direct factor Xa inhibitors.

In fact, a 2014 study found no difference in the anti-Xa activity between 11 patients on rivaroxaban who were given a 4-factor PCC (Beriplex®, the European brand name for Kcentra®) and 12 patients on rivaroxaban receiving saline.⁵ Though small, this is the best published in vivo data to date examining the effect of 4-factor PCC on the anti-Xa levels of patients on direct factor Xa inhibitors.

A theoretical concern with the use of PCCs is increased risk of thrombosis when the therapeutic effect of these direct oral anticoagulant (DOACs) is gone (half-life ~12 h) while the thrombogenic effects of PCCs persist (eg, in critically ill, postoperative, or sedentary patients).

The good news is that more specific reversal agents are in the pipeline. ¹ Stay tuned! 

 

References:

1. Dzik WH. “Reversal of oral factor Xa inhibitors by prothrombin complex concentrates: a re-appraisal.” J Thromb Haemost 2015;13 (Suppl 1):S187-94. https://www.ncbi.nlm.nih.gov/pubmed/26149022
2. Perzborn E, Heutmeier S, Laux V, et al. “Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant activated factor VII in vitro.” Thromb Res 2014 Apr;133:671-81. https://www.ncbi.nlm.nih.gov/pubmed/24529498
3. Eerenberg ES, Kamphuisen PW, Sijpkens MK, et al. “Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects.” Circulation 2011 Oct 4;124:1573-9. https://www.ncbi.nlm.nih.gov/pubmed/21900088
4. Zahir H, Brown KS, Vandell AG, et al. “Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate.” Circulation 2015 Jan 6;131:82-90. https://www.ncbi.nlm.nih.gov/pubmed/25403645
5. Levi M, Moore KT, Castillejos CF, et al. “Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers.” J Thromb Haemost 2014;12:1428-36. https://www.ncbi.nlm.nih.gov/pubmed/24811969

Contributed by Hanny Al-Samkari MD, Mass General Hospital, Boston, MA.

 

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