Thrombin inhib 
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  • ||||||||||  rivaroxaban / Generic mfg.
    Journal:  Activation of Piezo1 Channels in Compressed Red Blood Cells Augments Platelet-Driven Contraction of Blood Clots. (Pubmed Central) -  Jun 3, 2023   
    OKL-1111 is a procoagulant cyclodextrin with a currently unknown working mechanism that has potential to become a universal reversal agent for anticoagulants and platelet inhibitors. The results obtained demonstrate that the Piezo1 channel expressed on RBCs comprises a mechanochemical modulator of blood clotting that may be considered a potential therapeutic target to correct hemostatic disorders.
  • ||||||||||  bivalirudin / Generic mfg.
    Journal:  Assays to Monitor Bivalirudin. (Pubmed Central) -  May 23, 2023   
    Several assays can be used to monitor bivalirudin; these include the activated partial thromboplastin time (APTT), activated clotting time (ACT), ecarin clotting time (ECT), an ecarin-based chromogenic assay, thrombin time (TT), the dilute TT, and the prothrombinase-induced clotting time (PiCT). Drug concentrations can also be measured using liquid chromatography tandem mass spectrometry (LC/MS) and clotting or chromogenic-based assays with specific drug calibrators and controls.
  • ||||||||||  bivalirudin / Generic mfg., dabigatran etexilate / Generic mfg., argatroban / Generic mfg.
    Journal:  Ecarin-Based Methods for Measuring Thrombin Inhibitors. (Pubmed Central) -  May 23, 2023   
    Subsequently, this method has been more recently employed for measuring either the pharmacodynamic or pharmacokinetic properties of the oral direct thrombin inhibitor, dabigatran. In this chapter, the procedure for performing manual ECT and automated and manual ECA for measuring thrombin inhibitors is described.
  • ||||||||||  Journal:  An Overview of Heparin Monitoring with the Anti-Xa Assay. (Pubmed Central) -  May 23, 2023   
    The anti-Xa assay has shown additional benefits, such as faster time to achieve therapeutic levels, more consistent therapeutic levels, less dose adjustments, and, overall, less tests performed during therapy. However, poor interlaboratory agreement has been observed among anti-Xa reagents, highlighting that further work needs to be done to standardize this assay for use in patient heparin monitoring.
  • ||||||||||  Savaysa (edoxaban) / Daiichi Sankyo, Praxbind (idarucizumab) / Boehringer Ingelheim, AndexXa (coagulation factor Xa (recombinant), inactivated -zhzo) / Daiichi Sankyo, AstraZeneca
    Journal:  Reversal agents for current and forthcoming direct oral anticoagulants. (Pubmed Central) -  May 22, 2023   
    Reversal can be effected with specific agents, such as idarucizumab for dabigatran and andexanet alfa for apixaban, edoxaban, and rivaroxaban, or with non-specific agents, such as prothrombin complex concentrates, activated prothrombin complex concentrate, and recombinant activated factor VII. This paper (i) provides an update on when and how to reverse the DOACs, (ii) describes new reversal agents under development, and (iii) provides a strategic framework for the reversal of the factor XI inhibitors currently under investigation in phase three clinical trials.
  • ||||||||||  Thrombin activation of the factor XI dimer is a multi-staged process for each subunit (Room:516) -  May 18, 2023 - Abstract #ISTH2023ISTH_2286;    
    After this initial interaction, FXI undergoes conformational changes driven by binding of thrombin to the apple 1 domain in a secondary step to allow for migration towards the FXI cleavage site. The 1C10 binding site to the apple 1 domain supports this proposed trajectory of thrombin.
  • ||||||||||  Inhibition of thrombin receptor PAR-1 in endothelial colony forming cells modify their stemness and vasculogenic properties (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_2054;    
    Indeed, PAR-1 activation with PAR-1 activating peptide induced a significant decrease in CD133 expression while inhibition of PAR-1 with siRNA induced an increase in CD133 at mRNA levels but also at the protein level with a significant increase in intracellular expression of CD133. To confirm relevance of relationship between CD133 and PAR-1, we explored association between levels of both PAR-1 and CD133 in fast and slow fibroblasts prone to reprogrammation.
  • ||||||||||  dabigatran etexilate / Generic mfg.
    Platelet Activating and Fibrin Generating Properties of Distinct Vascular Smooth Muscle Cell Phenotypes (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_2022;    
    Interestingly, we observed significantly more erythrocytes present in and around thrombi formed on synthetic VSMCs, suggesting upregulated expression of receptors and/or ligands for erythrocyte adhesion by synthetic VSMCs. To determine whether thrombus formation on synthetic VSMCs is more driven by coagulation, whole blood was pre-treated with dabigatran, inhibiting thrombin.
  • ||||||||||  argatroban / Generic mfg., warfarin / Generic mfg.
    Use of DOAC-Stop to guide warfarin therapy in patients receiving argatroban (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_1832;    
    Warfarin requirements fluctuated (dose between 3-10mg), her INR became subtherapeutic for prolonged periods necessitating argatroban bridging. Due to previous stroke on therapeutic warfarin, risk of argatroban with INR < 2.5 was deemed high, thus DOAC-Stop INR was used to guide warfarin dosing without cessation of argatroban.
  • ||||||||||  Congenital FVII deficiency: analysis of phenotype and genotype (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_1803;    
    This mutation is already described and has been found to be associated with FVII deficiency and is considered pathogenic according to current ACMG2 criteria. On the other hand, a second missense variant c.583T>C rs372577568 p.Cys195Arg which is considered likely pathogenic.Conclusion(s): 1- Two coexisting heterozygous mutations causing severe FVII deficiency have been identified.2- Despite having the same mutation, there are differences in the capacity to generate thrombin.3- NGS is useful for genetic characterization of rare inherited coagulation disorders.
  • ||||||||||  Utility of Thrombin Generation Assay for inherited thrombophilia screening (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_1650;    
    There was also no statistically significant difference between ETP inhibition in the group with AT deficiency (n=5) and ETP inhibition in the group without risk factors. In contrast, ETP inhibition was significantly lower (p A variants (n=25), PC deficiency (n=17) or PS deficiency (n=6) compared with the group without risk factors.
  • ||||||||||  Characterization of anti-polyphosphate monoclonal antibodies (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_1276;    
    In competition binding assays for polyP using immobilized 2069, heparin and free polyP competed similarly. Antibody 2099 had a somewhat weaker affinity for polyP (Kd, 21 nM), but in competition assays, heparin was a far better competitor for this IgG than was free polyP.
  • ||||||||||  rivaroxaban / Generic mfg., dabigatran etexilate / Generic mfg., apixaban / Generic mfg.
    Pharmacogenomics of Novel Direct Oral Anticoagulants: Newly Identified Genetic Variants (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_1160;    
    The results suggest that the selected coding SNPs investigated in the present study are likely to contribute to the inter-individual variability in rivaroxaban, apixaban and dabigatran plasma concentrations. In addition, we also performed 16 subanalyses in order to identify the differences in the outcome of different comorbidities, age, dosage, liver and kidney function tests, and concomitant treatment.
  • ||||||||||  clopidogrel / Generic mfg.
    Inhibition of thrombin-mediated GPV cleavage ameliorates bleeding defects in a broad range of pathological conditions (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_1092;    
    DOM/B had no effect on thrombin-PAR-mediated platelet activation, but it significantly shortened time to fibrin formation and increased the amount of generated fibrin under flow in vitro, translating into accelerated in vivo thrombosis. DOM/B-treatment restored thrombosis and hemostasis in the complete absence of the two collagen receptors, GPVI and ?2?1.
  • ||||||||||  Relative Role of Auxiliary Plasma Protease Inhibitors in Thrombin Inhibition at Reduced Antithrombin Levels (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_870;    
    When AT was present at normal plasma concentration, addition of the other inhibitors at their normal plasma levels had minor impact on thrombin inhibition as evident by only 4 seconds decrease in the time to 50% inhibition. However, as the concentration of AT was lowered, the combined inhibitory role of other inhibitors became more pronounced.
  • ||||||||||  bivalirudin / Generic mfg.
    A Case of Bivalirudin Associated Diffuse Alveolar Hemorrhage following Percutaneous Coronary Intervention (Room:Exhibition) -  May 18, 2023 - Abstract #ISTH2023ISTH_727;    
    Although rare, the use of antithrombotic therapy is a known risk factor for DAH.2 Given the prevalence of bivalirudin during PCI, and the rarity of this complication, identifying risk factors remains crucial. Our case demonstrates age, female sex, elevated PCWP and prolonged bivalirudin use post-PCI as potential contributors to developing DAH.
  • ||||||||||  Review, Journal:  Thrombin, a Key Driver of Pathological Inflammation in the Brain. (Pubmed Central) -  May 17, 2023   
    Thrombin drives neuroinflammation through its pro-inflammatory activation of microglia, astrocytes, and endothelial cells. Due to the wide-ranging pro-inflammatory effects of thrombin in the brain, inhibiting thrombin could be an effective strategy for interrupting the inflammatory cascade which contributes to neurodegenerative disease progression and, as such, may be a potential therapeutic target for AD and other neurodegenerative diseases.
  • ||||||||||  Journal:  Production and Testing of RNA Origami Anticoagulants. (Pubmed Central) -  May 15, 2023   
    Here, we describe the detailed methods of producing and testing of such RNA origami anticoagulants. This method highlights the potential of RNA origami for biomedical applications.
  • ||||||||||  Hypercoagulability impairs plaque stability in diabetes-induced atherosclerosis (Station 8) -  May 13, 2023 - Abstract #ESC2023ESC_2418;    
    Congruently, more macrophages and fewer smooth muscle cells were observed within lesions of diabetic TMPro/Pro ApoE-/- mice. ConclusionThus, impaired TM function reduces plaque stability, a characteristic of hyperglycemia-associated plaques, thus suggesting the crucial role of impaired TM function in mediating diabetes-associated atherosclerosis.
  • ||||||||||  Interleukin 37 attenuates platelet activation and thrombosis formation (Science Box 1) -  May 13, 2023 - Abstract #ESC2023ESC_671;    
    IL-37 directly attenuated platelet activation and thrombosis formation by binding to platelet IL-18R? and IL-1R8 and regulating the downstream signaling pathways, suggesting the potential role of exogenous IL-37 protein to prevent platelet hyperactivity thrombotic complications in patients with low plasma IL-37 levels.
  • ||||||||||  fondaparinux / Generic mfg., argatroban / Generic mfg.
    Journal:  Positive Allosteric Modulation of Antithrombin's Inhibitory Activity by RNA Aptamers. (Pubmed Central) -  May 7, 2023   
    AT-16 induces a conformational change in AT that is different from that induced by heparin. This study demonstrates that an AT-specific RNA aptamer, AT-16, exhibits a positive allosteric modulator effect on AT's inhibition of factor Xa.
  • ||||||||||  Journal:  Simultaneous Inhibition of Thrombosis and Inflammation Is Beneficial in Treating Acute Myocardial Infarction. (Pubmed Central) -  May 2, 2023   
    Treatment reduced thrombin deposition, suppressed endothelial activation, inhibited inflammasome signaling pathways, and limited microvascular injury and vascular pruning in infarct border zones. Accordingly, thrombin inhibition with an extraordinarily potent but locally acting agent suggested a critical role for thrombin and a promising therapeutic strategy in cardiac IRI.
  • ||||||||||  Clinical guideline:  Recommendation on the Nomenclature for Anticoagulants: Updated Communication from the ISTH SSC Subcommittee on the Control of Anticoagulation. (Pubmed Central) -  May 2, 2023   
    Given that these emerging medications will likely have distinct risk-benefit profiles to the current direct oral anticoagulants, may have different routes of administration, and could be used for unique clinical conditions (e.g., hereditary angioedema), the ISTH subcommittee on Control of Anticoagulation assembled a writing group to make recommendations on the nomenclature of anticoagulant medications. With input from the broader thrombosis community, the writing group recommends that anticoagulant medications be described by the route of administration and specific target (e.g., oral Factor XIa inhibitor).
  • ||||||||||  rivaroxaban / Generic mfg., dabigatran etexilate / Generic mfg., warfarin / Generic mfg.
    Journal:  Exploring the Clinical Efficacy of Venous Thromboembolism Management in Saudi Arabian Hospitals: An Insight into Patient Outcomes. (Pubmed Central) -  Apr 28, 2023   
    The results of the study highlight the need for further research to determine the most effective therapeutic strategy for VTE management in Saudi Arabian hospitals. The findings also suggest that anticoagulation therapy, including oral anticoagulants, may increase the risk of VTE recurrence, while thrombolytic therapy and catheter-directed thrombolysis may lower the risk.