Management of rivaroxaban or apixaban associated major bleeding with prothrombin complex concentrates: a cohort study

Ammar Majeed, Anna Ågren, Margareta Holmström, Maria Bruzelius, Roza Chaireti, Jacob Odeberg, Eva-Lotta Hempel, Maria Magnusson, Tony Frisk and Sam Schulman

Key points

  • Prothrombin complex concentrates for the management of major bleeding on rivaroxaban or apixaban is an effective strategy in most cases.

  • Rate of thromboembolic complications in this setting is low and comparable to that seen in anticoagulation discontinuation without reversal.


There is uncertainty regarding the effectiveness and occurrence of thromboembolic events in patients treated with prothrombin complex concentrates (PCC) for management of major bleeding events (MBE) on rivaroxaban or apixaban. We investigated the effectiveness of PCC given for management of MBE on rivaroxaban or apixaban. Between 1/1/2014 and 1/10/2016, we prospectively included patients treated with PCC for management of MBE on rivaroxaban or apixaban. The effectiveness of PCC was assessed using the International Society of Thrombosis and Hemostasis' Scientific and Standardization Subcommittee criteria for the assessment of effectiveness of major bleeding management. Safety outcomes were thromboembolic events and all-cause mortality within 30 days after treatment with PCC. A total of 84 patients received PCC for the reversal of rivaroxaban or apixaban due to a MBE. PCC was given at a median (interquartile range) dose of 2000 IU (1500-2000). Intracranial hemorrhage (ICH) was the commonest site of bleeding requiring reversal (n=59, 70.2%), followed by gastrointestinal bleeding in 13 (15.5%) patients. Management with PCC was assessed as effective in 58 (69.1%) patients, and ineffective in 26 (30.9%) patients. Most patients with ineffective hemostasis with PCC had ICH (n=16, 61.5%). Two patients developed ischemic stroke occurring five and ten days after treatment with PCC. Twenty-seven (32%) patients died within 30 days after MBE. The administration of PCC for management of MBE associated with rivaroxaban or apixaban is effective in most cases and associated with a low risk of thromboembolism. Our findings are limited by the absence of a control group in the study.

  • Submitted May 2, 2017.
  • Accepted August 18, 2017.