Evidence-based Management of Major Bleeding in Patients Receiving Direct Oral Anticoagulants: An Updated Narrative Review on the Role of Specific Reversal Agents

Abstract

The indications of direct oral anticoagulants (DOACs) have expanded over the past 15 years. DOACs are effective and safe oral anticoagulants associated with lower bleeding risks and mortality than vitamin K antagonists. However, DOAC users are prone to a considerable bleeding risk, which can occur at critical sites or lead to severe life-threatening conditions. Recent statistics indicated that major bleeding occurs in up to 6.62 DOAC users per 100 treatment years. With the increased use of DOACs in clinical practice, DOAC-associated major bleeding is expected to be encountered more frequently in the emergency department. The current international guidelines recommend specific reversal agents for the management of DOAC users with severe bleeding to reverse the anticoagulant effect and restore normal hemostasis. An individualized assessment was incorporated in specific clinical situations to guide the decision pathway of major bleeding management. However, specific reversal agents are unavailable or have limited availability in many countries, which is expected to negatively impact the clinical outcomes of DOAC-associated major bleeding. Limited real-world evidence is available from these countries regarding the clinical outcomes of patients with DOAC-associated major bleeding. This narrative review provided an updated assessment of the evidence-based approaches for the management of major bleeding in DOAC users. We also explored the clinical outcomes of patients with major bleeding from clinical settings where specific reversal agents are unavailable.

Idarucizumab in dabigatran-treated patients with acute stroke: a review and clinical update

“…A meta-analysis done by Chaudhary et al ( 36 ) revealed an anticoagulation reversal rate of 82%, a mortality rate of 11%, and a thromboembolic rate of 5% after idarucizumab application in patients with ICH ( 36 ), which is in line with the RE-VERSE AD study results. Based on the analysis of available published data, all authors support the use of idarucizumab in ICH ( 34–37 , 39 ), which is also reflected in clinical practical guidelines written by Joglar et al ( 8 ). In a review by Al Aseri et al ( 34 ), authors additionally addressed the concern of limited availability of specific reversal agents in various countries and stressed the urgent need of availability and accessibility for developing local guidelines to direct their use ( 34 ).…”

“…Based on the analysis of available published data, all authors support the use of idarucizumab in ICH ( 34–37 , 39 ), which is also reflected in clinical practical guidelines written by Joglar et al ( 8 ). In a review by Al Aseri et al ( 34 ), authors additionally addressed the concern of limited availability of specific reversal agents in various countries and stressed the urgent need of availability and accessibility for developing local guidelines to direct their use ( 34 ). The final analysis from the Japanese postmarketing surveillance study in which 804 patients were included ( 41 ) confirmed previously reported data from an interim analysis ( 48 ) revealing the efficacy and safety of idarucizumab treatment in dabigatran-treated patients suffering from ICH ( 41 ).…”

“…Updated literature search for additional case reports and case series, trials, reviews, and guidelines extending the period of our previous exploration to 21/12/2023 using the same strategy and inclusion criteria, data extraction and outcomes, methodology, and statistical analysis ( 22 ) retrieved 16 articles ( 8 , 24 , 34–47 ) [six reviews ( 34–39 ), two original research articles ( 24 , 40 ), one postmarketing surveillance study ( 41 ), one clinical practice guidelines ( 8 ), one case report ( 42 ), and five case series ( 43–47 )].…”

“…Five review articles ( 34–37 , 39 ) addressed the use of idarucizumab regarding its use in ICH. A meta-analysis done by Chaudhary et al ( 36 ) revealed an anticoagulation reversal rate of 82%, a mortality rate of 11%, and a thromboembolic rate of 5% after idarucizumab application in patients with ICH ( 36 ), which is in line with the RE-VERSE AD study results.…”