The publication of positive new data and a need to minimise hospital visits during the COVID-19 pandemic has seen a general trend towards using more direct oral anticoagulants (DOACs), write Ankur Thapar, a consultant vascular surgeon, and Premalatha Sharavanan, consultant lead for vascular anaesthesia at Mid and South Essex Hospitals NHS Foundation Trust (Basildon, UK). Against this background, Thapar and Sharavanan outline what an interventionalist needs to know about this group of medications in 2021.
The landscape of antithrombotic therapy following vascular reconstruction has changed over the last year following the publication of VOYAGER-PAD1 and a recent Delphi consensus on antithrombotic therapy following deep venous intervention.2 Furthermore, in the wake of COVID-19, more patients and physicians have opted for DOACs over vitamin K antagonists to minimise hospital visits.
Regional anaesthetic practices have also been prioritised in the last year with the aim of minimising critical care admission, reducing the risk of pneumonia,3 and with new evidence for better patency in fistula formation.4 This primer aims to tell the interventionalist how DOACs work and how to manage them in the perioperative period.
How DOACs work
Apixaban, edoxaban, and rivaroxaban exert their effects on the common pathway through direct inhibition of activated factor X, which cleaves prothrombin. Hence monitoring is through an activated factor X assay.
Perioperative advice for antithrombotic therapy
Put simply, low-dose DOACs should be withheld for 24 hours before a procedure (e.g. rivaroxaban 2.5mg bd/10mg od, or apixaban 2.5mg bd/5mg bd). High-dose DOACs should be withheld for 48 hours (rivaroxaban 20mg od/15mg bd, or apixaban 10mg bd/10mg od). This is a major advantage over warfarin, as the requirement for bridging is much less frequent. In our institution, bridging is considered only for patients receiving therapeutic anticoagulation, for the following indications:
- Deep venous stent
- Venous thromboembolism (VTE) within the previous three months
- VTE whilst on anticoagulation
- Mechanical heart valve
- Atrial fibrillation patients with a stroke/transient ischaemic attack (TIA) in the last three months
- Atrial fibrillation patients with a previous stroke/TIA and ≥3 CHADSVASC2 risk factors (heart failure, hypertension, age >75 years, or diabetes)
In our institution, enoxaparin 1.5mg/kg od is self-administered at 0800 as a bridging therapy on days when an oral anticoagulant is not taken. Bridging is not required for low-dose DOACs.
Following an intervention, DOACs are not used in the first 24 hours, as reversal is difficult. Instead, therapeutic low molecular weight heparin (LMWH) or unfractionated intravenous heparin is safer in the immediate postoperative period.
Emergency surgery whilst anticoagulated with DOACs
If possible, surgery should be delayed to allow the plasma level of the drug to fall, as there are limited possibilities for reversal. The concentration of drug can be estimated from the dose of the drug, the time of last dose and the estimated glomerular filtration rate (eGFR).
- Coagulation tests: prothrombin time (PT), activated partial thromboplastim time (APTT), and thrombin time (TT) allow an approximate estimate of the levels of drug present in the circulation. A normal APTT and PT do not exclude the presence of significant concentrations of rivaroxaban, apixaban, or edoxaban in plasma.
- Andexanet alpha (recombinant activated factor X) is a specific reversal agent for apixaban and rivaroxaban, but is currently extremely expensive.
- Tranexamic acid 1g intravenously should be considered.
- Topical haemostatics should be considered.
- A tourniquet where possible should be considered.
- If andexanet alpha is unavailable, prothrombin complex concentrate (containing factors II, VII, IX, and X) can be used as an emergency empirical reversal agent.
- DOACs work through direct inhibition of factor Xa
- Low-dose DOACS should be stopped 24 hours preoperatively
- High-dose DOACs should be stopped 48 hours preoperatively
- DOACs should not be used in the immediate postoperative period
- Andexanet alpha is the specific reversal agent
- Bonaca MP, Fanelli F, Capell WH, et al. Rivaroxaban in peripheral artery disease after revascularization. NEJM 2020;382:1994–2004.
- Milinis K, Thapar A, Shalhoub J, et al. Antithrombotic therapy following venous stenting: International Delphi consensus. Eur J Vasc Endovasc Surg 2018;55(4):537–44.
- Hausman MS, Jewell ES, Engoren M. Does avoiding general anesthesia reduce the risk of postoperative complications. Anesth analg 2015;120(6):1405–12.
- Aitken E, Jackson A, Kearns R, et al. Effect of regional versus local anaesthesia on outcome after arteriovenous fistula creation: A randomised controlled trial. Lancet [Internet]. 388(10049):1067–74. Available from: http://dx.doi.org/10.1016/S0140-6736(16)30948-5
Ankur Thapar is a consultant vascular surgeon at Mid and South Essex Hospitals NHS Foundation Trust (Basildon, UK) and an honorary senior lecturer at Imperial College London (London, UK).
Premalatha Sharavanan is the consultant lead for vascular anaesthesia at Mid and South Essex Hospitals NHS Foundation Trust (Basildon, UK).