Balancing Risks and Benefits When Recommencing Oral Anticoagulants after Major Bleeding

Comment on: Restart of Anticoagulant Therapy and Risk of Thrombosis, Rebleeding, and Death after Factor Xa Inhibitor Reversal in Major Bleeding Patients Thromb Haemost 2021; 121(08): 1097-1106 DOI: 10.1055/a-1400-6159 Restart of Anticoagulant Therapy and Risk of Thrombosis, Rebleeding, and Death after Factor Xa Inhibitor Reversal in Major Bleeding Patients A significant growth in the prescribing of oral anticoagulants (OACs) has occurred over the last decade, largely due to their increasing role in stroke prevention, especially in the aging patients diagnosed with atrial fibrillation (AF).[ 1 ] Indeed, there has been a move away from traditional OACs (i.e., vitamin K antagonists) toward the more contemporary direct OACs (DOACs),[ 2 ] [ 3 ] which have been shown to be at least as effective as warfarin in stroke prevention, and have a lower rate of associated intracranial hemorrhage (ICH) and mortality in clinical trials[ 4 ] and real-world studies.[ 5 ] [ 6 ] [ 7 ] An inevitable double-edged sword exists with the prescribing of any anticoagulant, with an elevated thrombotic risk in patients not treated, but an increased hemorrhage risk in those that are. Safe, effective, and rapid-onset nonvitamin K oral anticoagulant (NOAC)-reversal agents are required should major hemorrhage occur, and new drugs have been developed specifically for this purpose.[ 8 ] [ 9 ] [ 10 ] However, studies assessing NOAC reversal fail to address what happens after the NOAC is reversed and the bleeding is under control. What new and growing risks exist in relation to having stopped NOAC therapy, which was designed to prevent thrombosis in the first instance? Underlying thrombotic risk factors have not resolved, and in some cases may be elevated in view of a new critical illness. Clinicians are forced to make decisions about timely but safe recommencement of the very drug which has contributed to the recent bleeding event. The most common major bleeding events that concern physicians in relation to OACs are gastrointestinal bleeding and ICH, with evidence in both cases that subsequent anticoagulation resumption is beneficial for reducing thrombotic events and mortality in the longer term.[ 11 ] [ 12 ] [ 13 ] [ 14 ] However, there is a lack of high-quality published data and evidence-based guidelines on how early resumption should occur, meaning that clinical practice is varied and outcomes poorly understood. In this issue of Thrombosis and Haemostasis , Milling et al aim to provide data around this challenging topic by performing a posthoc analysis on the DOAC reversal study, ANNEXA-4.[ 15 ] The original study recruited 352 patients with major bleeding while taking a DOAC who all received the reversal agent andexanet alfa.[ 8 ] In the current study the authors sought to clarify whether any benefit or harm could be observed in patients from the ANNEXA-4 trial where the treating clinician recommenced therapeutic OAC within 30 days. This was summarized in terms of event rates of thrombosis, hemorrhage (at least 3 days after primary bleed), and death ([ Fig. 1 ]). There were 100 patients who restarted OAC within 30 days, at a median of 10 days, with 83% restarting DOACs and 17% vitamin K antagonists.