Predictors of preprocedural direct oral anticoagulant levels in patients having an elective surgery or procedure

Abstract

The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) study prospectively evaluated a prespecified periprocedural-interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Logistic regression analyses were performed to identify clinical parameters associated with residual DOAC levels ≥30 ng/mL or ≥50 ng/mL. Patients undergoing low-bleed-risk procedures were more likely to have residual levels of ≥30 ng/mL and ≥50 ng/mL. For low-risk procedures, age ≥75 years, female sex, a creatinine clearance (CrCl) <50 mL/min, and an interruption of <36 hours were associated with a greater likelihood of levels ≥30 ng/mL, whereas age ≥75 years, female sex, a CrCl of <50 mL/min, and standard DOAC dosing were associated with levels ≥50 ng/mL. For high-risk procedures, weight of <70 kg, CrCl <50 mL/min, and standard DOAC dosing were associated with residual levels ≥30 ng/mL, whereas female sex was associated with levels ≥50 ng/mL. For low-risk procedures, apixaban was associated with a higher likelihood of levels ≥30 ng/mL as compared with dabigatran (P = .0019) and of levels ≥50 ng/mL when compared with rivaroxaban (P = .0003). For high-risk procedures, apixaban was marginally associated with a higher likelihood of residual levels ≥30 ng/mL when compared with dabigatran (P = .05), whereas rivaroxaban was associated with a higher likelihood of levels ≥30 ng/mL as compared with apixaban. Further study is required to determine whether adjustments to perioperative plans based on these clinical parameters could result in a lower risk of residual DOAC levels. The PAUSE trial was registered at www.clinicaltrials.gov as #NCT2228798.

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

“…[17][18][19] Some have also suggested DOAC measurements in patients the day prior to undergoing interventions with high bleeding risk (e.g., complex endoscopy, spinal or epidural anesthesia, thoracic surgery, abdominal surgery, major orthopaedic surgery or neurosurgery), 5,[20][21][22][23] although it should be noted that this approach of measuring DOACs is currently not supported by clinical evidence and the relevance of the current threshold is questioned. 24 Specifically, although the "Perioperative Anticoagulant Use for Surgery Evaluation" (PAUSE) study reported acceptable bleeding rates with their clinically defined anticoagulant interruption strategies and defined thresholds, that is, analyses were done for residual DOAC levels 30 ng/mL and 50 ng/mL, 25,26 it is not known what DOAC level would be considered "safe" to undergo a surgical procedure or intervention and with the vast majority of patients, a wait time period appears to be safe. 25,26 With limited data on patients with a body mass index (BMI) >40 kg/m 2 , DOAC pharmacokinetic and/or pharmacodynamic measurements in this population may be considered.…”

“…24 Specifically, although the "Perioperative Anticoagulant Use for Surgery Evaluation" (PAUSE) study reported acceptable bleeding rates with their clinically defined anticoagulant interruption strategies and defined thresholds, that is, analyses were done for residual DOAC levels 30 ng/mL and 50 ng/mL, 25,26 it is not known what DOAC level would be considered "safe" to undergo a surgical procedure or intervention and with the vast majority of patients, a wait time period appears to be safe. 25,26 With limited data on patients with a body mass index (BMI) >40 kg/m 2 , DOAC pharmacokinetic and/or pharmacodynamic measurements in this population may be considered. 27,28 In addition, many elderly patients with non-valvular atrial fibrillation may acutely develop decompensated heart insufficiency with increase of liver enzymes, decreased intestinal blood flow and develop an unpredictable pharmacokinetic profile which may lead to an increased bleeding risk.…”

Challenges in Patient Blood Management for Cardiac Surgery: A Narrative Review

“…The PAUSE study subanalysis from Shaw [ 68 ] in 2020 was performed to identify clinical parameters associated with residual DOAC levels of more than 30 ng/mL. Older age, female sex, low weight, renal dysfunction and shorter interruption were associated with risk of elevated preprocedural DOAC levels and the authors concluded that further study is required to determine whether adjustments to perioperative interruption based on these clinical parameters could result in a lower risk of residual DOAC levels.…”

“…For vitamin K antagonists (VKA), the time will depend on the specific agent used: the last dose of acenocoumarol should be taken 3 to 4 days before surgery, the last dose of warfarin 6 days before surgery and phenprocoumon should be interrupted up to 10 days prior to surgery [50,56]. The PAUSE study subanalysis from Shaw [68] in 2020 was performed to identify clinical parameters associated with residual DOAC levels of more than 30 ng/mL. Older age, female sex, low weight, renal dysfunction and shorter interruption were associated with risk of elevated preprocedural DOAC levels and the authors concluded that further study is required to determine whether adjustments to perioperative interruption based on these clinical parameters could result in a lower risk of residual DOAC levels.…”

Thromboprophylaxis Measures to Prevent Venous Thromboembolism in Hospitalized Patients

“…59 Using this feature should be considered, specially for patients who will undergo surgery and those affected by a thrombotic event in the last 30 days, for which anticoagulation should be stopped. 60,61 Removable filters should be used in individuals who have temporary restrictions on anticoagulants, and should remain for approximately 2 weeks. 62 Continuous use of these filters therapeutically is not indicated for patients not selected with DVT and candidates for the use of anticoagulants.…”