Thrombotic events and rebleeding after hemorrhage in patients taking direct oral anticoagulants for non-valvular atrial fibrillation

PLoS One. 2021 Nov 29;16(11):e0260585. doi: 10.1371/journal.pone.0260585. eCollection 2021.

Abstract

Several direct oral anticoagulants have been developed to prevent cardiogenic thrombosis in patients with atrial fibrillation, on the other hand, have the complication of bleeding. Since clinical course after bleeding with direct oral anticoagulant remains unclear, the present retrospective cohort study was to clarify the course after hemorrhage among patients receiving direct oral anticoagulants. Among all 2005 patients prescribed dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017, subjects comprised 96 patients with non-valvular atrial fibrillation who experienced relevant bleeding during direct oral anticoagulant therapy (Bleeding Academic Research Consortium type 2 or above). The clinical course after hemorrhage was reviewed to examine whether rebleeding or thrombotic events occurred up to the end of December 2019. Gastrointestinal bleeding was the most frequent cause of initial bleeding (57 patients, 59%). Rebleeding occurred in 11 patients (4.5%/year), with gastrointestinal bleeding in 10 and subarachnoid hemorrhage in 1. All rebleeding occurred in patients who resumed anticoagulation therapy. Another significant factor related with rebleeding included past history of gastrointestinal bleeding. On the other hand, major adverse cardiac and cerebrovascular events occurred in 6 patients older than 75 years old or more (2.5%/year), with systemic thrombosis in 4 and cardiac death in 2. All 4 patients with systemic thrombosis withheld anticoagulants after index bleeding, although only 10 patients withheld anticoagulation therapy. Rebleeding should be taken care of when anticoagulants are resumed after bleeding, particularly among patients who initially experienced gastrointestinal bleeding. Systemic thrombosis occurred at a high rate when anticoagulant therapy was withheld after bleeding.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Dabigatran / adverse effects
  • Dabigatran / therapeutic use
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Hemorrhage / chemically induced*
  • Humans
  • Male
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use
  • Pyridines / adverse effects
  • Pyridines / therapeutic use
  • Pyridones / adverse effects
  • Pyridones / therapeutic use
  • Retrospective Studies
  • Rivaroxaban / adverse effects
  • Rivaroxaban / therapeutic use
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use
  • Thrombosis / complications
  • Thrombosis / drug therapy*

Substances

  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridines
  • Pyridones
  • Thiazoles
  • apixaban
  • Rivaroxaban
  • Dabigatran
  • edoxaban

Grants and funding

The authors received no specific funding for this work.