Rivaroxaban reversal with prothrombin complex concentrate or tranexamic acid in healthy volunteers. (2nd December 2017)

• Record Type: Journal Article
• Authors: Levy, J. H.; Moore, K. T.; Neal, M. D.; Schneider, D.; Marcsisin, V. S.; Ariyawansa, J.; Weitz, J. I.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 16:Number 1(2018)
• Page Start: 54
• Page End: 64
• Publication Date: 2017-12-02
• Subjects: anticoagulants -- antidotes -- hemorrhage -- prothrombin complex concentrate -- rivaroxaban -- tranexamic acid; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13894
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract : Essentials Specific reversal agents for managing severe factor Xa inhibitor‐associated bleeding are lacking. We assessed 4‐factor‐prothrombin complex concentrate (4F‐PCC) and tranexamic acid (TXA). 4F‐PCC, but not TXA, reduced the prothrombin time and increased endogenous thrombin potential. These agents may be viable options for reversal of therapeutic doses of rivaroxaban. Summary: Background: Oral activated factor X inhibitors such as rivaroxaban are widely used, but specific reversal agents are lacking. Although four‐factor prothrombin complex concentrate (4F‐PCC) and tranexamic acid (TXA) are sometimes used to manage serious bleeding, their efficacy is unknown. Prior studies in healthy subjects taking rivaroxaban revealed that 4F‐PCC partially reverses the prolonged prothrombin time (PT), and fully restores the endogenous thrombin potential (ETP). The effect of TXA has not been evaluated. Methods: In this double‐blind, parallel‐group study, 147 healthy volunteers given rivaroxaban 20 mg twice daily for 3 days were randomized after their morning dose on day 4 to receive intravenous 4F‐PCC (50 IU kg −1 ), TXA (1.0 g), or saline. Standardized punch biopsies were performed at baseline and after 4F‐PCC, TXA or saline administration. Reversal was assessed by measuring bleeding duration and bleeding volume at biopsy sites, and by determining the PT and ETP. Results: As compared with saline, 4F‐PCC partially reversed the PT and completely reversed the ETP, whereas TXA had no effect. Neither 4F‐PCC nor TXA reduced bleeding duration or volume. All treatments were well tolerated, with no recorded adverse events. Conclusions: Although 4F‐PCC reduced the PT and increased the ETP in volunteers given supratherapeutic doses of rivaroxaban, neither 4F‐PCC nor TXA influenced punch biopsy bleeding.