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Background: Since the late 2000s, Europe has granted approval for various thrombotic risk‐related uses of direct oral anticoagulants (DOACs). Unlike traditional anticoagulants, DOACs do not necessitate routine coagulation monitoring. Nevertheless, clinical practice often encounters bleeding events associated with these medications, making the need for effective reversal strategies evident. Objectives: The study aims to take stock of current reversal strategies for DOACs, with a particular emphasis on the latest compounds that have been developed or are currently under development. Methods: For obtaining information regarding the ongoing reversal strategies and the compounds under development, we referred to ClinicalTrials website, PubMed, and Google Scholar. Results: In 2024, two specific antidotes to DOACs have already received approval when reversal of anticoagulation is needed owing to life‐threatening or uncontrolled bleeding: idarucizumab that reverses the effects of dabigatran, and andexanet alfa, designed to counteract activated factor X inhibitors such as apixaban and rivaroxaban. Furthermore, ciraparantag, a potential universal reversal agent, is currently in advanced stages of clinical development. Concerns remain regarding the safety of specific reversal agents, especially concerning the risk of thrombosis. Additionally, the cost of these antidotes remains high. Consequently, nonspecific strategies to counteract anticoagulant medications, including activated charcoal, hemodialysis, and concentrates of coagulation factors, still have utility. Conclusion: With the validation of specific and nonspecific antidotes, DOACs could supplant traditional oral anticoagulants. This progress represents a significant advancement in anticoagulation therapy. However, ongoing research is crucial to address remaining safety concerns of the specific reversion agents of DOACs in clinical practice. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to assess differentially expressed blood proteins between patients with active RA and patients in remission after MTX treatment, with the aim of identifying a biomarker of MTX resistance (MTXR). Methods Two populations of RA patients treated with a stable dose of s.c. MTX for at least 3 months were constituted according to the DAS28: remission (DAS28 < 2.6; n  = 24) and active disease (DAS28 > 3.2; n  = 32). The two groups of RA patients were homogeneous regarding their epidemiological characteristics, except for the duration of treatment, which was longer in the remission group. After collection of a blood sample, plasma protein digestion was performed, followed by untargeted proteomics analysis. Then, a targeted analysis was performed to confirm the results of the untargeted approach. Results Untargeted proteomics analysis revealed eight plasma proteins that were differentially expressed between the two groups of patients. Among them, triosephosphate isomerase (TPI-1) and glucose-6-phosphate isomerase (GPI), which are main actors in glycolysis, were found down-regulated in the active group. This result was confirmed for TPI-1 in the targeted proteomics analysis. Conclusion A first step was achieved in the search for biomarkers of MTXR, with the identification of two actors in glycolysis (TPI-1 and GPI). The next step will be to confirm these results in a larger cohort, including samples from treatment-naive patients, to assess the predictive potential of these protein markers. [ABSTRACT FROM AUTHOR]

Introduction: The knowledge of dabigatran levels is helpful for decision‐making in specific situations such as urgent surgery or when the question of reversal arises (uncontrolled bleeding, eligibility for thrombolysis). However, a limited number of observational studies are available regarding comparisons between quantification methods. The objective of the study was to compare dabigatran plasma levels using three assays including the reference method (high‐performance liquid chromatography coupled with mass spectrometry), focusing on the agreement around the 30–50 ng/mL clinically relevant thresholds. Methods: Sixty healthy volunteers from DRIVING trial (NCT01627665) were given a single 300‐mg dabigatran etexilate dose. Serial blood samplings were performed at pre‐defined time points (0 to 24 h). We analyzed plasma samples using ultra‐performance‐liquid chromatography coupled with tandem mass spectrometry (UPLC‐MS) (dabigatran reference method); ii/diluted thrombin time (dTT) (Hemoclot‐DTI‐Hyphen‐Biomed); iii/ecarin‐based chromogenic assay (ECA‐II‐Stago). Results: Nine hundred sixty samples were analyzed using the three assays (2759 values). dTT and ECA‐II values were highly correlated with those of UPLC‐MS (Deming regression). Most values >50 ng/mL were higher using dTT and ECA‐II compared to UPLC‐MS: biases were constant, +14% and +16% with dTT and ECA‐II, respectively (Bland–Altman plots), suggesting that active metabolites accounted for ~15% of thrombin inhibition. Regarding values <30 ng/mL, 30–50 ng/mL, or ≥50 ng/mL, the agreement probability between dTT and ECA‐II was of 90.6% [88.4–92.5] (Cohen's kappa coefficient 0.84). Conclusion: dTT and ECA‐II assays rapidly provide accurate dabigatran‐level results for clinical practice, both assays being suitable in emergency, taking into account the thrombin inhibitory effect of dabigatran metabolites. [ABSTRACT FROM AUTHOR]