DOACs- balance between thrombosis and bleeding - A Review
- reversal agents
How to Cite
Bleeding is a common side effect of anticoagulant use. However, the majority of bleeding events are not life-threatening and can be managed conservatively. The first step in managing any significant bleeding event is to temporarily stop using the anticoagulant. The aim of this review was to determine the appropriate management strategy for an acutely bleeding patient on DOACs. Direct oral anticoagulants (DOACs) are now widely used in treatment of venous thromboembolism (VTE) and are recommended first-line over vitamin K antagonists (VKAs) in non-cancer associated VTE. Until recently, supportive measures and infusion of clotting factors were the only available options for reversal of DOACs. Within the last 4 years, approval of specific antidotes has led to hopes for improved outcomes in DOAC-related acute bleeding, however limitations remain including cost, availability and "real-world" data. In severe and life-threatening bleeding events, use of non-specific (e.g. PCC) or specific (e.g. idarucizumab, andexanet alpha) reversal agents are recommended. However, further data is needed to compare outcomes between these two management strategies and identify the cost-effectiveness of these various strategies.
2. Kearon C, Akl EA, Omelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016;149:315-52.
3. Godier A, Niclot A, Le Bonniec B, et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology 2012;116:94-102.
4. Zhou W, Zorn M, Nawroth P, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban. Stroke 2013;44:771-8.
5. Zhou W, Schwarting S, Illanes S, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke 2011;42:3594-99.
6. Lambourne MD, Eltringham-Smith LJ, Gataiance S, Arnold DM, Crowther MA, Sheffield WP. Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. J Thromb Haemost 2012;10:1830-40.
7. Martin AC, Le Bonniec B, Fischer AM, et al. Evaluation of recombinant activated factor VII, prothrombin complex concentrate, and fibrinogen concentrate to reverse apixaban in a rabbit model of bleeding and thrombosis. Int J Cardiol 2013;168:4228-33.
8. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011;124:1573-79.
9. Schulman S, Ritchie B, Nahirniak S, et al. Reversal of dabigatran-associated major bleeding with activated prothrombin concentrate: a prospective cohort study. Thromb Res 2017;152:44-48.
10. Dager WE, Roberts AJ, Nishijima DK. Effect of low and moderate dose FEIBA to reverse major bleeding in patients on direct oral anticoagulants. Thromb Res 2019;173:71-76.
11. Majeed A, Agren A, Holmstrom M, et al. Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study. Blood 2017;130:1706-12.
12. Smith MN, Deloney L, Carter C, Weant KA, Eriksson EA. Safety, efficacy, and cost of four-factor prothrombin complex concentrate (4F-PCC) in patients with factor Xa inhibitor-related bleeding: a retrospective study. J Thrombo Thrombolysis 2019;48:250-55.
13. Pollack CV Jr, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal – full cohort analysis. N Eng J Med 2017;377:431-41.
14. Connolly SJ, Crowther M, Eikelboom JW, et al. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Eng J Med 2019;380:1326-35.
15. Cuker A, Burnett A, Triller D, et al. Reversal of direct oral anticoagulants: guidance from the Anticoagulation Forum. Am J Hematol 2019;94:697-709.
16. Levy JH, Ageno W, Chan NC, et al. When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb Haemost 2016;14:623-27.
17. Staerk L, Fosbol EL, Lamberts M, et al. Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study. Eur Heart J 2018;39:1698-1705a.
18. Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv 2018;2:3257-91.
19. Bosevski M et al. Venous thrombology. Ars lamina, Skopje 2016
20. Hanigan S, Barnes GD. Managing Anticoagulant-related Bleeding in Patients with Venous Thromboembolism. Available at https://www.acc.org/latest-in-cardiology/articles/2019/10/07/14/29/managing-anticoagulant-related-bleeding-in-patients-with-venous-thromboembolism.