Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: Thrombin or factor-Xa inhibitors. Recommendations of the Working Group on perioperative haemostasis and the French Study Group on thrombosis and haemostasis

Abstract

Direct oral anticoagulants (DOAs)--inhibitors of thrombin or factor-Xa--are expected to replace vitamin K antagonists in most of their indications. Patients receiving long-term treatment with DOAs are likely to be exposed to elective or emergency surgery or invasive procedures. Owing to the present lack of experience in such conditions, we cannot make recommendations, but only propose perioperative management for optimal safety regarding the risk of bleeding and thrombosis. DOAs may increase surgical bleeding, they have no validated antagonists, they cannot be monitored by simple standardized laboratory assays and their pharmacokinetics vary significantly between patients. Although DOAs differ in many respects, the proposals in the perioperative setting need not be specific to each. For procedures with low haemorrhagic risk, a therapeutic window of 48 hours (last administration 24 hours before surgery, restart 24 hours after) is proposed. For procedures with medium or high haemorrhagic risk, we suggest stopping DOAs 5 days before surgery to ensure complete elimination in all patients. Treatment should be resumed only when the risk of bleeding has been controlled. In patients at high thrombotic risk (e.g. those in atrial fibrillation with a history of stroke), bridging with heparin (low molecular-weight heparin, or unfractionated heparin, if the former is contraindicated) is proposed. In an emergency, the procedure should be postponed for as long as possible (minimum 1-2 half-lives) and non-specific antihaemorrhagic agents, such as recombinant human activated factor VIIa or prothrombin complex concentrates should not be given for prophylactic reversal due to their uncertain benefit-risk.

Practical aspects of new oral anticoagulant use in atrial fibrillation

“…Italian experts have recently suggested that patients with previous deep hemispheric the last dose of rivaroxaban administered once daily. 29 The other approach has suggested that the first dose of LMWH should be given 24 h after the last dose of the TSOAC to limit the risk of bleeding and one might recommend this option in particular in subjects with lower CrCl values who were taking dabigatran. It is advisable to administer the last therapeutic dose of LMWH 24 h before surgery, and this should be half dose if was given once daily, like during bridging therapy in patients on VKAs.…”

Gestion péri-opératoire des patients traités par antithrombotiques en chirurgie orale. Argumentaire

“…En dehors du champ strict de la chirurgie orale, des propositions et des suggestions ont été émises par le Groupe d'intérêt en hémostase périopératoire (GIHP) et le GEHT [259,260]. Dans le cadre de la chirurgie programmée, la poursuite du traitement par AOD est la règle en instaurant une fenêtre théra-peutique.…”

“…Dans tous les autres cas, un relais en postopératoire par héparine est en général non nécessaire. Les AOD ayant un délai d'action très rapide, il ne doit y avoir aucun chevauchement avec le traitement par l'héparine [259,260] À la vue des profils d'efficacité et de sécurité des AOD dans les essais de phase III par rapport aux anticoagulants Devant l'insuffisance des données de la littérature, le groupe de travail a élaboré les recommandations concernant la gestion des AOD en chirurgie orale à partir d'une position dégradée de celle des AVK. Une bonne prise en charge des patients sous AOD en vue d'une intervention chirurgicale ou d'un acte invasif repose principalement sur des critères pharmacologiques tels le nombre de prise par jour, la demi-vie du produit, l'heure de la dernière prise, le délai et la dose de la première dose administrée après la chirurgie [16,259,260].…”

“…Agence française de sécurité sanitaire des produits de santé (Afssaps) 5 [2], [3], [4], [6], [7] Agence nationale de la sécurité du médicament (Ansm) 3 [9], [10], [11] American Dental Association (ADA) 1 [121] American College of Chest Physicians 7 [12], [61], [85], [86], [91], [111], [125] American Heart Association (AHA) 1 [121] British Dental Society (BDS) 1 [244] Bristish Committee for Standards in Haematology 2 [32], [207] International Society of Thrombosis and Haemostasis (ISTH) 1 [111] Groupe Etude de l'Hémostase et de la Thrombose (GEHT) de la Société d'Hématologie 3 [ 122], [123], [124], [259], [260] Haute Autorité de Santé (HAS) 34 [130], [131], [132], [133], [134], [135], [136], [137], [138], [139], [140], [141], [142], [143], [144], [145], [146], [147], [148], …”

Laboratory Testing of Hemostasis

“…Specifi c assays for the measurement of NOAC plasma concentrations are available in specialized laboratories and should be ordered in case of hemorrhagic events or emergent surgeries (Sié et al 2011 ;Pernod et al 2013 ).…”