Restart of Anticoagulant Therapy and Risk of Thrombosis, Rebleeding, and Death after Factor Xa Inhibitor Reversal in Major Bleeding Patients

Thromb Haemost. 2021 Aug;121(8):1097-1106. doi: 10.1055/a-1400-6159. Epub 2021 Apr 14.

Abstract

Background: Lack of data on balancing bleeding and thrombosis risk causes uncertainty about restarting anticoagulants after major bleeding. Anticoagulant reversal trials offer prospectively gathered data after major bleeding with well-documented safety events and restarting behavior.

Objectives: To examine the relationship of restarting anticoagulation with thrombosis, rebleeding, and death.

Methods: This is a posthoc analysis of a prospective factor Xa inhibitor reversal study at 63 centers in North America and Europe. We compared outcomes of restarted patients with those not restarted using landmark and time-dependent Cox proportional hazards models. Outcomes included thrombotic and bleeding events and death and a composite of all three.

Results: Of 352 patients enrolled, oral anticoagulation was restarted in 100 (28%) during 30-day follow-up. Thirty-four (9.7%) had thrombotic events, 15 (4.3%) had bleeding events (after day 3), and 49 (14%) died. In the landmark analysis comparing patients restarted within 14 days to those not, restarting was associated with decreased thrombotic events (hazard ratio [HR] = 0.112; 95% confidence interval [CI]: 0.001-0.944; p = 0.043) and increased rebleeding (HR = 8.39; 95% CI: 1.13-62.29; p = 0.037). The time-dependent Cox model showed evidence for a reduction in a composite (thrombotic events, bleeding, and death) attempting to capture net benefit (HR = 0.384; 95% CI: 0.161-0.915; p = 0.031).

Conclusion: This analysis provides modest evidence that restarting anticoagulation in factor Xa inhibitor-associated major bleeding patients is correlated with reduced risk of thrombotic events and increased risk of rebleeding. There is low-level evidence of net benefit for restarting. A randomized trial of restarting would be appropriate.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulant Reversal Agents / adverse effects
  • Anticoagulant Reversal Agents / therapeutic use*
  • Anticoagulation Reversal* / adverse effects
  • Anticoagulation Reversal* / mortality
  • Drug Administration Schedule
  • Europe
  • Factor Xa / administration & dosage*
  • Factor Xa / adverse effects
  • Factor Xa Inhibitors / administration & dosage*
  • Factor Xa Inhibitors / adverse effects
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / drug therapy*
  • Humans
  • Male
  • North America
  • Prospective Studies
  • Recombinant Proteins / administration & dosage*
  • Recombinant Proteins / adverse effects
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Thrombosis / diagnosis
  • Thrombosis / mortality
  • Thrombosis / prevention & control*
  • Time Factors
  • Treatment Outcome

Substances

  • Anticoagulant Reversal Agents
  • Factor Xa Inhibitors
  • PRT064445
  • Recombinant Proteins
  • Factor Xa