Reversal of Dabigatran in patients with intracerebral haemorrhage – a narrative review

D Suryaprabha

Senior Executive-Clinical Research, Kauvery Hospitals, India

Correspondence: Tel.: +91 98414 86267; email: suryaprabha@kauveryhospital.com

Abstract

Background: The objective of this review is to provide an overview on the current development of the specific reversal agent for Dabigatran. Anticoagulation is key to the treatment/prevention of thromboembolic events. The primary complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt anticoagulation reversal. High Cost and limited availability are the main disadvantages of reversal of Dabigatran.

Methods: The decision to reverse anticoagulation should weigh the benefit-risk ratio of supporting haemostasis versus post- reversal thrombosis.

Conclusion: High Cost and limited availability are the main disadvantages of reversal of oral anticoagulation.

Keywords

Bleeding, Reversal of anticoagulation, Idarucizumab, Dabigatran

Background

Anticoagulation is key to the treatment/prevention of thromboembolic events. The primary complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt anticoagulation reversal [1] The decision to reverse anticoagulation should weigh the benefit-risk ratio of supporting haemostasis versus post-reversal thrombosis [1].

Oral anticoagulants are broadly used in the prevention of thromboembolic events and stroke in patients with atrial fibrillation, lone (non-valvular) or with underlying valvular heart disease, mechanical heart valves, those undergoing treatment for deep venous thrombosis, patients with pulmonary embolism, as well as in the prevention of venous thromboembolism in medical and orthopedic surgery patients [2,3]. However NOACs are not yet approved for Atrial Fibrillation with valvular heart disease and those with mechanical heart valves.

In this review, the authors searched national and international literature to identify currently available data on the salient features of the management of Dabigatran reversal and its administration.

The reversal of Dabigatran 

Activated charcoal could be useful by helping reduce the absorption of Dabigatran (if the last dose was less than 2 h before an emergency). Haemostatic strategies using specific Dabigatran reversal agents should always be considered for patients with major bleeding, if available [4].

The thrombin inhibitor

Patients under dabigatran may present normal or increased Activated Partial Thromboplastin Time or Thrombin Time). Removal through dialysis is possible, taking at least 4 h to eliminate approximately 60 to 70% of the drug. Therefore, patients who are hemodynamically unstable due to bleeding are not candidates for dialysis. Reversal of dabigatran is achieved with Idarucizumab.

reversal-of-dabigatran-image1

Fig 1.   Reversal Mechanism of Dabigatran.

Idarucizumab is a humanized monoclonal antibody fragment that b,inds dabigatran and acts as a specific reversal agent in cases of emergency surgery or urgent procedures, or major bleeding, life-threatening bleeding, or uncontrolled bleeding [5]. It takes two and a half hours for bleeding cessation after the intravenous administration of 5 g and 24 h for complete reversal [5]. However, some patients, especially those with comorbid renal failure, may rebound and need a repeated dose [5]. High cost, limited availability, and the lack of clinical experience limit the use of Idarucizumab and other specific reversal agents for dabigatran.

Conclusion

High Cost and limited availability are the main disadvantages of Reversal of Dabigatran. Emergency situations, such as trauma, bleeding, and urgent surgery, involve the reversal of anticoagulants. Reversal is achieved by the administration of hemoderivatives such as Prothrombin Complex Concentrates(PCCs) and Fresh Frozen Plasma (FFP), and specific agents against Dabigatran. Patients taking Dabigatran should receive specific reversal agents (Idarucizumab). In cases of non-availability of specific reversal agents, PCC or Activated Prothrombin Complex Concentrate ( aPCC) could be considered based on limited evidence.

References

[1] TJ Milling, Pollack CV. A review of guidelines on anticoagulation reversal across different clinical scenarios – Is there a general consensus? Am J Emerg Med. 2020;38(9):1890-903.

[2] Tadros R, Shakib S. Warfarin indications, risks and drug interactions. Aus Fam Phys. 2010;39:476-9.

[3] Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e278S-325S.

[4] Tomaselli GF, Mahaffey KW, Cuker A, et al. 2020 ACC Expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: A report of the american college of cardiology solution set oversight committee. J Am Coll Cardiol. 2020;76:594-622.

[5] Pollack CV, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal – Full Cohort Analysis. N Engl J Med. 2017;377:431-41.

Suryaprabha-new

D. Suryaprabha

Senior Executive-Clinical Research

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