2025 Guidelines for direct oral anticoagulants: a practical guidance on the prescription, laboratory testing, peri-operative and bleeding management

Abstract

Direct oral anticoagulants (DOACs) are widely prescribed to prevent and treat venous and arterial thromboembolism, supported by published evidence, and are preferred over warfarin in many guidelines. Although the risk of major bleeding, in particular intracranial haemorrhage (ICH), is decreased with DOACs, gastrointestinal bleeding is increased with some DOACs, and the case fatality rate of bleeding remains high. Therefore, it is important to (i) prescribe DOACs appropriately, (ii) have strategies to manage major bleeding including the use of specific reversal agents and (iii) interrupt and resume DOACs for procedures. The main recommendations are as follows: (i) Select the appropriate dose of DOAC according to indications and consider patient factors to minimise bleeding risks; (ii) DOACs do not require routine laboratory testing; (iii) for life-threatening uncontrollable bleeding, specific agents can be used to reverse the anticoagulant effects of DOACs; and (iv) DOACs can be interrupted for planned procedures without the need for 'bridging' with low-molecular-weight heparin (LMWH). The anticoagulant effects of DOACs can be reversed with specific agents, such as andexanet for apixaban and rivaroxaban and idarucizumab for dabigatran. If not available, pro-haemostatic agents such as prothrombin complex concentrates or activated prothrombin complex concentrates can be considered. DOACs can be interrupted and resumed for procedures without the need for 'bridging' with LMWH.

Keywords: direct oral anticoagulant; major bleeding; perioperative anticoagulation; reversal agent.

Figure 1

Management of direct oral anticoagulant (DOAC)‐related bleeding. *Clinically significant bleeding – reduction in Hb ≥20g/L, transfusion of ≥2 units of red cells and haemodynamically stable. **Life‐threatening bleeding – bleeding in critical area or organ (e.g. intraocular, intracranial, intraspinal, compartment syndrome, retroperitoneal or pericardial, hypotension not responding to resuscitation). †Give as IV bolus at rate 30 mg/min over 15 min (low dose) or 30 min (high dose), followed by continuous infusion of 4 mg/min (low dose) or 8 mg/min (high dose) for 120 min. High dose should be used for those taking rivaroxaban ≥10 mg or unknown within 8 h (or if time unknown) and apixaban >5 mg or unknown within 8 h (or unknown time); all others should receive low‐dose protocol. #This is an off‐licence use of factor eight inhibitor bypass activity (FEIBA) and PCC; the thrombotic complications with these agents when used for this indication is unclear. 4F‐PCC, four‐factor prothrombin complex concentrate; aPTT, activated partial thromboplastin time; FBC, full blood count; PT, prothrombin time; TT, thrombin time.