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 studies2-4; 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!
- 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
- 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
- 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
- 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
- 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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