Anne-Sophie Dincq

Estimation of dabigatran plasma concentrations in the perioperative setting. An ex vivo study using dedicated coagulation assays.

The perioperative management of dabigatran is challenging, and recommendations based on activated partial thromboplastin time (aPTT) and thrombin time (TT) are unsatisfactory. Dedicated coagulation tests have limitations at plasma concentrations < 50 ng/ml. Therefore, a more sensitive test, which is available 24/7, is required. It was the aim of this study to investigate the performance of the Hemoclot Thrombin Inhibitors® LOW (HTI LOW) kit, a diluted thrombin time, and the STA® - ECA II(ECA-II) kit, a chromogenic variant of the ecarin clotting time, that were developed to measure low dabigatran concentrations, compared to reference dabigatran analysis by liquid chromatography tandem mass-spectrometry (LC-MS/MS). This study included 33 plasma samples from patients treated with dabigatran etexilate who had plasma concentrations < 200 ng/ml. HTI LOW and ECA-II were performed along with HTI, aPTT (STA®-C. K.Prest® and SynthasIL®) and TT (STA® - Thrombin). All procedures were performed according to recommendations by the manufacturers. Linear (or curvilinear) correlations and Bland-Altman analyses were calculated. For free dabigatran concentrations < 50 ng/ml, the R² of linear correlations were 0.69, 0.84 and 0.61, with HTI, HTI LOW and ECA-II, respectively. The R² for TT, STA®-C. K.Prest® and SynthasIL® were 0.67, 0.42 and 0.15. For HTI, HTI LOW and ECA-II, Bland-Altman analyses revealed mean differences of -6 ng/ml (95 %CI: -25-14 ng/ml), 1 ng/ml (95 %CI: -18-19 ng/ml) and -1 ng/ml (95 %CI: -25-23 ng/ml), demonstrating that tests dedicated to measuring low concentrations are more accurate than HTI. In conclusion, the use of HTI LOW or ECA-II to assess low plasma dabigatran concentrations is supported by our findings.

Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study.

Aims Patients receiving direct oral anticoagulants (DOACs) frequently undergo elective invasive procedures. Their management is challenging. We aimed to determine the optimal duration of DOAC discontinuation that ensures a minimal anticoagulant effect during the procedure. Methods and results This prospective multicentre study included 422 DOAC-treated patients requiring an invasive procedure. Pre-procedural DOAC concentration ([DOAC]) and routine haemostasis assays were performed to determine i/the proportion of patients who achieved a minimal pre-procedural [DOAC] (≤30 ng/mL) according to the duration of DOAC discontinuation, ii/the predictors of minimal [DOAC] and, iii/the ability of routine assays to predict minimal [DOAC]. Lastly, we assessed the predictors of peri-procedural bleeding events. The duration of DOAC discontinuation ranged from 1 to 218 h and pre-procedural [DOAC] from ≤30 to 527 ng/mL. After a 49-72-h discontinuation, 95% of the [DOAC] were ≤30 ng/mL. A 72-h discontinuation predicted concentrations ≤30 ng/mL with 91% specificity. In multivariable analysis, duration of DOAC discontinuation, creatinine clearance <50 mL/min and antiarrhythmics were independent predictors of minimal pre-procedural [DOAC] (concordance statistic 0.869; 95% confidence interval: 0.829-0.912). Conversely, routine haemostasis assays were poor predictors. Last, creatinine clearance <50 mL/min, antiplatelets and high-bleeding risk procedures were predictors of bleeding events. Conclusion A last DOAC intake 3 days before a procedure resulted in minimal pre-procedural anticoagulant effect for almost all patients. Moderate renal impairment, especially in dabigatran-treated patients, and antiarrhythmics in anti-Xa-treated patients should result in a longer DOAC interruption. In situations requiring testing, routine assays should not replace DOAC concentration measurement.

Is Thrombin Time useful for the assessment of dabigatran concentrations? An in vitro and ex vivo study

Is Thrombin Time useful for the assessment of dabigatran concentrations? An in vitro and ex vivo study

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

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 experts opinions.

Estimation of Rivaroxaban Plasma Concentrations in the Perioperative Setting in Patients With or Without Heparin Bridging

Introduction: Estimation of residual rivaroxaban plasma concentrations may be requested before invasive procedures and some patients at high thromboembolic risk will have a bridging therapy with heparins when rivaroxaban is interrupted. Objective: The objective of this study was to assess the performance of the STA-Liquid Anti-Xa assay (STA LAX) and the low and normal procedures of the Biophen Direct Factor Xa Inhibitors (DiXaI) assay, in patients with and without bridging with low-molecular-weight heparins (LMWHs). Materials and Methods: Seventy-nine blood samples were collected from 77 patients on rivaroxaban at CTROUGH or before an invasive procedure. Rivaroxaban plasma concentrations were estimated using Biophen DiXaI, Biophen DiXaI LOW, and STA LAX and compared to liquid chromatography coupled with mass spectrometry (LC-MS/MS) measurements. Stratifications were performed according to heparin bridging. Results: The Biophen DiXaI LOW and STA LAX showed better correlation with LC-MS/MS measurements than Biophen DiXaI in patients not bridged with LMWH (R: 0.97, 0.96, and 0.91, respectively). However, the performance of Biophen DiXaI LOW and STA LAX decreased when residual LMWH activity was present (R: 0.18 and 0.19 respectively) demonstrating that these tests are not specific to rivaroxaban. Conclusion: In patients not bridged with LMWH, we suggest to use the Biophen DiXaI LOW and STA LAX for the estimation of rivaroxaban concentrations <50 ng/mL. These results should be confirmed on a larger cohort of patients. Patients bridged with LMWH have inaccurate estimates of low levels of rivaroxaban and the 3 assays studied should not be used to estimate if it is safe to perform a procedure.

Perioperative management of patients on direct oral anticoagulants

Direct oral anticoagulants (DOACs) have been licensed worldwide for several years for various indications. Each year, 10–15% of patients on oral anticoagulants will undergo an invasive procedure and expert groups have issued several guidelines on perioperative management in such situations. The perioperative guidelines have undergone numerous updates as clinical experience of emergency management has increased and perioperative studies including measurement of residual anticoagulant levels have been published. The high inter-patient variability of DOAC plasma levels has challenged the traditional recommendation that perioperative DOAC interruption should be based only on the elimination half-life of DOACs, especially before invasive procedures carrying a high risk of bleeding. Furthermore, recent publications have highlighted the potential danger of heparin bridging use when DOACs are stopped before an invasive procedure.As antidotes are progressively becoming available to manage severe bleeding or urgent procedures in patients on DOACs, accurate laboratory tests have become the standard to guide their administration and their actions need to be well understood by clinicians.This review aims to provide a systematic approach to managing patients on DOACs, based on recent updates of various perioperative guidance, and highlighting the advantages and limits of recommendations based on pharmacokinetic properties and laboratory tests.

Jet Ventilation during Rigid Bronchoscopy in Adults: A Focused Review.

The indications for rigid bronchoscopy for interventional pulmonology have increased and include stent placements and transbronchial cryobiopsy procedures. The shared airway between anesthesiologist and pulmonologist and the open airway system, requiring specific ventilation techniques such as jet ventilation, need a good understanding of the procedure to reduce potentially harmful complications. Appropriate adjustment of the ventilator settings including pause pressure and peak inspiratory pressure reduces the risk of barotrauma. High frequency jet ventilation allows adequate oxygenation and carbon dioxide removal even in cases of tracheal stenosis up to frequencies of around 150 min−1; however, in an in vivo animal model, high frequency jet ventilation along with normal frequency jet ventilation (superimposed high frequency jet ventilation) has been shown to improve oxygenation by increasing lung volume and carbon dioxide removal by increasing tidal volume across a large spectrum of frequencies without increasing barotrauma. General anesthesia with a continuous, intravenous, short-acting agent is safe and effective during rigid bronchoscopy procedures.

Idarucizumab for the treatment of hemorrhage and dabigatran reversal in patients requiring urgent surgery or procedures

ABSTRACT Introduction: Idarucizumab is a specific antagonist for dabigatran etexilate (DE). The recent market authorization of idarucizumab in Europe and the USA may reassure prescribers of DE, as it can increase the safety of the emergency management of patients taking this anticoagulant. However, idarucizumab use should be limited to specific indications to avoid unnecessary risks to patients and costs to healthcare systems. Areas covered: The authors provide an overview of idarucizumab development and its pharmacokinetic and pharmacodynamic properties. The results of the clinical phase III trial RE-VERSE AD and a review of recent case reports of idarucizumab use in emergency contexts are also discussed. Expert opinion: Although idarucizumab has shown clear efficacy in reversing dabigatran-induced coagulopathy, its overall effects on patient outcome have not been proven. Information regarding the clinical context in which patients on DE are admitted for emergency treatment, and accurate laboratory tests of dabigatran plasma level during reversal may inform selection and help with the follow-up of patients who may benefit from idarucizumab. Idarucizumab should be integrated into protocol for the emergency management of patients on DE. Furthermore, the benefit of idarucizumab in specific indications such as acute ischemic stroke should be investigated.

Fully Covered Metallic Stents for the Treatment of Benign Airway Stenosis.

Introduction. We herein report our experience with new fully covered self-expanding metallic stents in the setting of inoperable recurrent benign tracheobronchial stenosis. Methods. Between May 2010 and July 2014, 21 Micro-Tech® FC-SEMS (Nanjing Co., Republic of Korea) were placed in our hospital in 16 patients for inoperable, recurrent (after dilatation), and symptomatic benign airway stenosis. Their medical files were retrospectively reviewed in December 2014, with focus on stents tolerance and durability data. Results. Twenty-one stents were inserted: 13 for posttransplant left main bronchus anastomotic stricture, seven for postintubation tracheal stenosis, and one for postlobectomy anastomotic stricture. Positioning was easy for all of them. Stents were in place for a mean duration of 282 days. The most common complications were granulation tissue development (35%), migration (30%), and sputum retention (15%). Fifty-five % of the stents (11/20) had to be removed because of various complications, without difficulty for all of them. None of the patients had life-threatening complications. Conclusion. Micro-Tech FC-SEMS were easy to position and to remove. While the rate of complications requiring stent removal was significant, no life-threatening complication occurred. Further studies are needed to better define their efficacy and safety in the treatment of benign airway disease.

Double-Lumen Tubes for Tracheostomized Patients

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