Management of Non-Vitamin K Antagonist Oral Anticoagulants in the Perioperative Setting

Abstract

The field of oral anticoagulation has evolved with the arrival of non-vitamin K antagonist oral anticoagulants (NOACs) including an anti-IIa agent (dabigatran etexilate) and anti-Xa agents (rivaroxaban and apixaban). The main specificities of these drugs are predictable pharmacokinetics and pharmacodynamics but special attention should be paid in the elderly, in case of renal dysfunction and in case of emergency. In addition, their perioperative management is challenging, especially with the absence of specific antidotes. Effectively, periods of interruption before surgery or invasive procedures depend on half-life and keeping a permanent balance between bleeding and thromboembolic risks. In addition, few data regarding the link between plasma concentrations and their effects are provided. Routine laboratory tests are altered by NOACs and quantitative measurements are not widely performed. This paper provides a review on the management of NOACs in the perioperative setting, including the estimation of the bleeding and thrombotic risk, the periods of interruption, the indication of heparin bridging, the usefulness of laboratory tests before surgery or invasive procedure, and the time of resuming. Most data are based on expert's opinions.

Sessile Serrated Adenoma of the Appendix and Perforated Cecal Lymphoma in a Nonagenarian on Novel Anticoagulant Undergoing Emergent Surgery: The Challenges, Decision Making and Management of a Rare Case

“…RE-COVER study of dabigatran [47], EINSTEIN study of rivaroxaban [48] and AMPLIFY study of apixaban [49]) the rate of major bleeding complications with NOACs range from 2.1 to 3.6%/year [50]. Some authors have added risk score such as HAS-BLED [51][52][53] or HEMORR2HAGES [52,53] as contributing factors. These score include patient-related variables such as hypertension, renal function and age.…”

“…Currently no consensual guidelines for management of patients on NOACs achieved in emergent surgery settings. Knowledge and integration of the patient's coagulation status is the key to proper decision making [52,[55][56][57]. Management of bleeding during emergency surgery is challenging due to the absence of specific antidotes.…”

What's New in Anticoagulation

“…Two thirds of a rivaroxaban dose undergoes metabolic degradation in the liver, of which half is eliminated renally and half is removed via the hepatobiliary route in the feces. 4 The influence of renal function on rivaroxaban is considered to be moderate, and rivaroxaban is prescribed at oral dosages of 20 mg/d with evening meals (if CrCl >50 mL/min) or 15 mg/d with evening meals (if CrCl=15-50 mL/min), and is not recommended only in cases of severe renal impairment (CrCl <15 mL/min) when used for the prevention of AF-related stroke in patients with AF. 4,8 17th Symposium on Cardiac Arrhythmias…”

Determination of Apixaban Levels in Human Plasma by a High-Throughput Liquid Chromatographic Tandem Mass Spectrometry Assay / Determinarea rapidă a apixabanului în plasma umană prin cromatografie de lichide de înaltă performanță cuplată cu spectrometrie de masă în tandem

“…Moreover, unplanned surgery or postoperative periods would benefit from precise evaluations of hemorrhagic risk, as apixaban plasma concentrations proved to be linearly correlated to its anti-Xa activity, over a wide dose range of apixaban (0.5 -50 mg), for both patients and healthy subjects [3]. Furthermore, for dabigatran and rivaroxaban, two other novel oral anticoagulants, several algorithms are available for the management of the bleeding risk associated with emergency surgery and invasive procedures, considering the drugs plasma concentrations, obtained through the use of sensitive analytical methods [15,16].…”

“…Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is the reference method used in therapeutic monitoring of novel direct oral anticoagulants due its precision, accuracy, sensitivity and robustness [14][15][16][17]. There are several pharmacokinetics studies of apixaban [7,[18][19][20][21][22][23] and assessments of different laboratory tests [17,24] that used LC-MS/MS for quantification of apixaban in human plasma.…”