Effect of heparins, direct oral anticoagulants, and factor XII/factor XI inhibitors on catheter-initiated thrombin generation in platelet-rich plasma: an in vitro study.

Background: Invasive endovascular procedures often require anticoagulation to prevent device-associated thrombosis. High doses of unfractionated heparin (UFH) are the gold standard. The efficacy of factor (F)XII(a) and FXI(a) inhibitors remains unexplored.

Revisiting the Environmental Impact of Inappropriate Clinical Laboratory Testing: A Comprehensive Overview of Sustainability, Economic, and Quality of Care Outcomes.

Background: The use of laboratory resources has seen a substantial increase in recent years, driven by automation and emerging technologies. However, inappropriate use of laboratory testing, encompassing both overuse and underuse, poses significant challenges.

Content: This review explores the complex interplay between patient safety, economic, and environmental factors-known as the "triple bottom line" or "3Ps" for people, profit, and planet-associated with inappropriate use of laboratory resources.

Uninterrupted DOACs Approach for Catheter Ablation of Atrial Fibrillation: Do DOACs Levels Matter?

Most patients present for catheter ablation of atrial fibrillation (CAAF) with residual or full effect of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). In daily practice, it has been observed that the activated clotting time (ACT) was actually poorly sensitive to the effect of DOACs and that patients on DOACs required more unfractionated heparin (UFH) to achieve the ACT target of 300 s during the procedure, leading some authors to worry about potential overdosing. Conversely, we hypothesize that these higher doses of UFH are necessary to achieve adequate hemostasis during CAAF regardless of the residual effect of DOACs.

Monitoring of Unfractionated Heparin Therapy in the Intensive Care Unit Using a Point-of-Care aPTT: A Comparative, Longitudinal Observational Study with Laboratory-Based aPTT and Anti-Xa Activity Measurement.

Continuous intravenous unfractionated heparin (UFH) is administered routinely in the intensive care unit (ICU) for the anticoagulation of patients, and monitoring is performed by the activated partial thromboplastin time (APTT) or anti-Xa activity. However, these strategies are associated with potentially large time intervals before dose adjustments, which could be detrimental to the patient. The aim of the study was to compare a point-of-care (POCT) version of the APTT to (i) laboratory-based APTT and (ii) measurements of anti-Xa activity in terms of correlation, agreement and turnaround time (TAT).

Impact of centrifugation on thrombin generation in healthy subjects and in patients treated with direct oral anticoagulants.

Introduction: Double centrifugation before freezing is recommended before thrombin generation assays (TGA). However, this procedure is not mandatory for routine hemostasis tests, precluding the use of these samples for TGA. The aim of this study is to assess the impact of single and double centrifugation on TGA performed on frozen samples from healthy volunteers (HVs) and patients receiving direct oral anticoagulants (DOACs).

The Impact of Strong Inducers on Direct Oral Anticoagulant Levels.

Purpose: The concomitant use of direct oral anticoagulants (DOAC) and strong P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) inducers may lead to reduced DOAC levels and therapeutic failure. This study aimed to describe DOAC concentrations in patients receiving strong P-gp and CYP3A4 inducers, in relation to individual risk factors for high or low DOAC levels.

Methods: We retrospectively identified hospitalized patients simultaneously receiving a DOAC and carbamazepine, phenobarbital, phenytoin, or rifampicin between 2016 and 2021.

Prothrombotic hemostasis disturbances in patients with severe COVID-19: Individual daily data.

This data article accompanies the manuscript entitled: "Prothrombotic Disturbances of hemostasis of Patients with Severe COVID-19: a Prospective Longitudinal Observational Cohort Study" submitted to by the same authors. We report temporal changes of plasma levels of an extended set of laboratory parameters during the ICU stay of the 21 COVID-19 patients included in the monocentre cohort: CRP, platelet count, prothrombin time; Clauss fibrinogen and clotting factors II, V and VIII levels, D-dimers, antithrombin activity, protein C, free protein S, total and free tissue factor pathway inhibitor, PAI-1 levels, von Willebrand factor antigen and activity, ADAMTS-13 (plasma levels); and of two integrative tests of coagulation (thrombin generation with ST Genesia) and fibrinolysis (global fibrinolytic capacity - GFC). Regarding hemostasis, we used double-centrifuged frozen citrated plasma prospectively collected after daily performance of usual coagulation tests.

[Management of the thrombotic risk associated with COVID-19: what is the role of the hemostasis laboratory?].

COVID-19 is associated with disturbances of hemostasis in the laboratory and an increased thrombotic risk. Routine laboratory tests - activated partial thromboplastin time (aPTT), prothrombin time, Clauss fibrinogen and D-dimers levels measurement - are used for the evaluation of the thrombotic risk and the monitoring of hemostasis, but are subject to several drawbacks that may affect the reliability and clinical relevance of the delivered results. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment.

Effects of Time-Interval since Blood Draw and of Anticoagulation on Platelet Testing (Count, Indices and Impedance Aggregometry): A Systematic Study with Blood from Healthy Volunteers.

Platelet count, indices (mean volume, young-immature platelet fraction) and aggregation are widely used laboratory parameters to investigate primary hemostasis. We performed a systematic, thorough evaluation of the influence of the time-interval since blood draw from 20 healthy individuals and of the anticoagulation of collected blood on such parameters. Blood was anticoagulated with citrate, K-ethylenediaminetetraacetic acid (EDTA) and hirudin and analyzed 5, 30, 60, 120 and 180 min after blood draw.

Evaluation of a new thromboplastin reagent STA-NeoPTimal on a STA R Max analyzer for the measurement of prothrombin time, international normalized ratio and extrinsic factor levels.

Introduction: We aimed at evaluating the performance of a new prothrombin time (PT) reagent (STA-NeoPTimal) with two other PT reagents (STA-Neoplastine R and STA-Neoplastine CI Plus) and the reference PT reagent used in our laboratory (ReadiPlasTin).

Methods: Evaluation consisted in intra- and interassay precision assessment, determination of sensitivity to unfractionated heparin (UFH) or enoxaparin in spiked samples and to direct oral anticoagulants (DOACs) in patients (n = 43). Method comparison of the 4 PT reagents, factor II, V, VII and X assays was tested on normal (n = 20) and abnormal samples: VKA (n = 47), preoperative (n = 23), liver failure (n = 12) and burned patients (n = 37).

Assessment of low plasma concentrations of apixaban in the periprocedural setting.

Introduction: Estimation of residual apixaban plasma concentrations may be requested in the management of emergencies. This study aims at assessing the performance of specific anti-Xa assays calibrated with apixaban on real-life samples with low apixaban plasma concentrations (<30 ng/mL) and on-treatment ranges, with and without interference of low-molecular-weight heparin (LMWH).

Methods: 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 was tested on 134 blood samples, collected from patients on apixaban, wherefrom 74 patients received LMWH after apixaban cessation.

Reduction of Preoperative Waiting Time before Urgent Surgery for Patients on P2Y Inhibitors Using Multiple Electrode Aggregometry: A Retrospective Study.

P2Y inhibitor discontinuation is essential before most surgical interventions to limit bleeding complications. Based on pharmacokinetic data, fixed discontinuation durations have been recommended. However, as platelet function recovery is highly variable among patients, a more individualized approach based on platelet function testing (PFT) has been proposed.

Evaluation of the DOAC-Stop® Procedure to Overcome the Effect of DOACs on Several Thrombophilia Screening Tests.

The impact of direct oral anticoagulants (DOACs) on laboratory assays used for thrombophilia testing (e.g., antithrombin, protein S, protein C, lupus anticoagulant and activated protein-C resistance) is a well-known issue and may cause false-positive and -negative results.

Assessment of the analytical performances and sample stability on ST Genesia system using the STG-DrugScreen application.

Background: Thrombin generation testing has been used to provide information on the coagulation phenotype of patients. The most used technique is the calibrated automated thrombogram (CAT) but it suffers from a lack of standardization, preventing its implementation in routine. The ST Genesia is a new analyzer designed to assess thrombin generation based on the same principle as the CAT.

Development of new methodologies for the chromogenic estimation of betrixaban concentrations in plasma.

Introduction: Chromogenic anti-Xa assays are the most appropriate tests to estimate the amount of betrixaban in plasma but the sensitivity of available tests is limited and improvements are needed to encompass the on-therapy range.

Methods: Betrixaban was spiked at concentrations ranging from 0 to 500 ng/mL in plasma from healthy donors. Three commercial tests were used (Biophen DiXaI , STA Liquid Anti-Xa, and HemosIL Liquid Anti-Xa), and adaptation of their sample dilution scheme was performed.

Periprocedural management of anticoagulation for atrial fibrillation catheter ablation in direct oral anticoagulant-treated patients.

Background: Guidelines recommend performing atrial fibrillation (AF) catheter ablation without interruption of a direct oral anticoagulants (DOACs) and to administer unfractionated heparin (UFH) for an activated clotting time (ACT) ≥300 seconds, by analogy with vitamin K antagonist (VKA). Nevertheless, pharmacological differences between DOACs and VKA, especially regarding ACT sensitivity and UFH response, prevent extrapolation from VKA to DOACs.

Hypothesis: The level of anticoagulation at the time of the procedure in uninterrupted DOAC-treated patients is unpredictable and would complicate intraprocedural UFH administration and monitoring.

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

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.

An optimized dRVVT-based assay to estimate the intensity of anticoagulation in patients treated with direct oral anticoagulants.

Background: The dilute Russell's viper venom time (dRVVT) has been suggested for the assessment of the intensity of anticoagulation of all direct oral anticoagulants (DOACs). This study aimed to compare the performance of an optimized liquid-stable dRVVT-based DOAC assay (DRVV-DOAC) on clinical samples before and after mixing these with normal pooled plasma (NPP).

Methods: Forty-one apixaban, 25 dabigatran, 56 rivaroxaban and 49 vitamin K antagonists (VKAs) plasma samples were included for retrospective analysis.

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.

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 C or before an invasive procedure.