Perioperative management of patients receiving non-vitamin K antagonist oral anticoagulants: up-to-date recommendations

Abstract

Indications of non-vitamin K antagonist oral anticoagulants (NOACs), consisting of two types: direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitor (rivaroxaban, apixaban, and edoxaban), have expanded over the last few years. Accordingly, increasing number of patients presenting for surgery are being exposed to NOACs, despite the fact that NOACs are inevitably related to increased perioperative bleeding risk. This review article contains recent clinical evidence-based up-to-date recommendations to help set up a multidisciplinary management strategy to provide a safe perioperative milieu for patients receiving NOACs. In brief, despite the paucity of related clinical evidence, several key recommendations can be drawn based on the emerging clinical evidence, expert consensus, and predictable pharmacological properties of NOACs. In elective surgeries, it seems safe to perform high-bleeding risk surgeries 2 days after cessation of NOAC, regardless of the type of NOAC. Neuraxial anesthesia should be performed 3 days after cessation of NOACs. In both instances, dabigatran needs to be discontinued for an additional 1 or 2 days, depending on the decrease in renal function. NOACs do not require a preoperative heparin bridge therapy. Emergent or urgent surgeries should preferably be delayed for at least 12 h from the last NOAC intake (better if > 24 h). If surgery cannot be delayed, consider using specific reversal agents, which are idarucizumab for dabigatran and andexanet alfa for rivaroxaban, apixaban, and edoxaban. If these specific reversal agents are not available, consider using prothrombin complex concentrates.

Peroralinių Antikoaguliantų Vartojimas Perioperaciniu Laikotarpiu

“…Tokiu atveju slopinamas trombino susidarymas ir sustabdoma išorinė bei vidinė krešėjimo kaskados [6][7][8]. Xa faktoriaus inhibitoriai yra greito veikimo peroraliniai antikoaguliantai, kurių bioprieinamumas siekia 50-100 proc., o didžiausia koncentracija plazmoje pasiekiama per 1-4 valandas [2,3,[6][7][8][9][10]. Rivaroksabano, apiksabano, edoksabano didžioji dalis yra metabolizuojama kepenyse per citochromo P450 CYP3A4 ir CYP2J2 fermentų sistemą [7,11].…”

“…Metabolitų ekskrecija daugiausia vyksta per biliarinę sistemą (apie 60-75 %), mažesnė vaistų metabolitų dalis pašalinami per inkstus (20-66 %). Skiriant šių antikoaguliantų pacientams, kurių kepenų ir inkstų funkcija yra sutrikusi, reikėtų atsižvelgti į kuo ilgesnę vaisto veikimo trukmę, o pacientams, sergantiems 4-5 stadijos lėtine inkstų liga, Xa faktoriaus inhibitoriai yra kontraindikuotini [2,3,6,7,9,10].…”

“…Šis trombino inhibitorius nėra metabolizuojamas kepenyse, todėl neturi sąveikos su kitais vaistais, kurie veikia citochromų fermentų sistemą. Dabigatranas yra konjuguojamas ir šalinamas per inkstus su šlapimu (apie 80%), o eliminacijos pusperiodis siekia 12-17 valandų [2,3,6,7,9,10,12]. Pacientams, sergantiems 4-5 stadijos lėtine inkstų liga, vaisto eliminacijos pusperiodis gali siekti iki 28-34 valandų, todėl vaistas yra kontraindikuotinas dėl didelės kraujavimo rizikos [3,7,12].…”

Bleeding disorders in implant dentistry: a narrative review and a treatment guide

“…In older studies, the death rate of patients treated with DOACs who experienced severe bleeding was similar to or even lower compared to patients treated with vitamin K antagonists, despite the lack of availability of antidotes [ 68 ]. Two antidotes were approved: idarucizumab to dabigatran and andexanet alfa to rivaroxaban / apixaban reversal [ 69 , 70 ]. However, in addition to the high cost of antidotes, it should be noted that the incidence of thromboembolic events increased dramatically to as high as 18% after administration of the approved antidotes [ 71 ].…”

“…Therefore, in the case of urgent interventions requiring surgery within hours, delaying surgery by at least 4 h (pharmacologically reasonable 12–24 h) after last DOAC administration should be considered, because a substantial amount of the drug is eliminated within this period of time [ 70 , 96 ]. Overall, as discussed above, bridging is currently not recommended with DOAC, although either short discontinuation or continuation of DOAC appears to be appropriate for interventions with low bleeding risk such as dental surgical procedures.…”