Thrombin inhib 
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  • ||||||||||  rivaroxaban / Generic mfg., dabigatran etexilate / Generic mfg., apixaban / Generic mfg.
    Journal:  Calibrated automated thrombogram II: removing barriers for thrombin generation measurements. (Pubmed Central) -  Aug 31, 2021   
    Furthermore, both the CAT-II method and ST-Genesia using the same calibration method were able to detect the effect of all oral anticoagulants. Taken together, applying a new calibration method is a significant improvement for monitoring patients on direct thrombin inhibitors while not introducing any bias to results obtained on other types of samples.
  • ||||||||||  Journal:  Sulfotyrosine-Mediated Recognition of Human Thrombin by a Tsetse Fly Anticoagulant Mimics Physiological Substrates. (Pubmed Central) -  Aug 28, 2021   
    Using X-ray crystallography, we show that the N-terminal sulfated segment of TTI binds the basic exosite II of thrombin, establishing interactions similar to those of physiologic substrates, while the C-terminal segment abolishes the catalytic activity of thrombin. This non-canonical mode of inhibition, coupled with its potency and small size, makes TTI an attractive scaffold for the design of novel antithrombotics.
  • ||||||||||  rivaroxaban / Generic mfg.
    Journal:  A multi-in-one strategy with glucose-triggered long-term antithrombogenicity and sequentially enhanced endothelialization for biological valve leaflets. (Pubmed Central) -  Aug 28, 2021   
    Herein, a multi-in-one strategy was established to modify biological valves with long-term antithrombogenicity and sequentially enhanced endothelialization triggered by glucose, in which the direct thrombin inhibitor rivaroxaban (RIVA)-loaded nanogels were embedded and the detachable polyethylene glycol (PEG) was grafted...Sequentially, PEG gradually peeled off under the local weak acidic environment, which ultimately resulted in the endothelialization enhancement. Within such multi-in-one strategy, the biological valve leaflets induced long-term anticoagulant performance, gradually enhanced endothelialization and improved tissue affinity, including anti-calcification and anti-inflammation, indicating the potential of the response sequence matching between materials and tissues after implantation, which might improve performance of biological heart valves.
  • ||||||||||  bivalirudin / Generic mfg., argatroban / Generic mfg.
    Clinical, Journal:  Direct Thrombin Inhibitors as an Alternative to Heparin During Catheter Ablation: A Multicenter Experience. (Pubmed Central) -  Aug 20, 2021   
    Unlike heparin, bivalirudin effectively blocked TIP by inhibiting the thrombin-induced S1P increment and S1PR2 expression, suggesting the novel endothelial protective effect of bivalirudin under pathological procoagulant circumstance. In this multicenter series, intravenous DTIs were safely used as an alternative to heparin for left-sided catheter ablation.
  • ||||||||||  [VIRTUAL] Citrullination: Inhibit, Identify, and Install (Room: Zoom Room 26) -  Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_8338;    
    Inhibition of SERPIN activity is highly significant as it triggers increased protease activity, thereby activating multiple processes including tissue remodeling, altered blood coagulation, and the activation of the complement cascade. Finally, I will describe our efforts to site-specifically incorporate citrulline into proteins.
  • ||||||||||  Journal:  Combining flavin photocatalysis with parallel synthesis: a general platform to optimize peptides with non-proteinogenic amino acids. (Pubmed Central) -  Aug 12, 2021   
    To gain general access to NPAA-containing peptides, we developed a first-generation platform that merges contemporary flavin photocatalysis with parallel synthesis to simultaneously make, purify, quantify, and even test up to 96 single-NPAA peptide variants via the unique combination of boronic acids and a dehydroalanine residue in a peptide. We showcase the power of our newly minted platform to introduce NPAAs of diverse chemotypes-aliphatic, aromatic, heteroaromatic-directly into peptides, including 15 entirely new residues, and to evolve a simple proteinogenic peptide into an unnatural inhibitor of thrombin by non-classical peptide SAR.
  • ||||||||||  Clinical, Journal, Real-world evidence:  Patients with haemophilia A with inhibitors in China: a national real-world analysis and follow-up. (Pubmed Central) -  Aug 11, 2021   
    In patients who did not undergo ITI, the inhibitors turned negative in 17·7%, and patients with low peak inhibitor titre were more likely to acquire negative titre spontaneously (odds ratio 11·524, 95% confidence interval 5·222-25·432; P = 0·000). We recorded that 3·2% of the patients died from haemophilia-related life-threatening bleeding.
  • ||||||||||  Journal:  Structure-function of anticoagulant TIX-5, the inhibitor of Factor Xa-mediated FV activation. (Pubmed Central) -  Aug 11, 2021   
    The structure-function properties of TIX-5 are in perfect agreement with a protein that inhibits the FXa-mediated activation on a phospholipid surface. The present elucidation of the mechanism of action of TIX-5 will aid in deciphering the processes involved in the initiation phase of blood coagulation.
  • ||||||||||  dabigatran etexilate / Generic mfg.
    Journal:  Dabigatran and The Risk of Staphylococcus Aureus Bacteremia- A Nationwide Cohort Study. (Pubmed Central) -  Aug 8, 2021   
    The present elucidation of the mechanism of action of TIX-5 will aid in deciphering the processes involved in the initiation phase of blood coagulation. Treatment with dabigatran was associated with a significantly lower incidence rate of SAB compared with treatment with factor Xa-inhibitors.
  • ||||||||||  Journal:  Effect of Yiqi Huoxue Granules on Platelet Activation Induced by Thrombin. (Pubmed Central) -  Aug 3, 2021   
    Compared with the control group, the platelet aggregation rate, PAR-1 protein expression, phosphorylation of ERK1/2, and p38 protein in the YQHX group decreased (P 0.05). YQHX suppresses the platelet activation induced by thrombin by inhibiting PAR-1 expression.
  • ||||||||||  Clinical, Review, Journal:  Anticoagulation Strategies in Extracorporeal Circulatory Devices in Adult Populations. (Pubmed Central) -  Jul 30, 2021   
    Given the substantial thrombotic risks associated with extracorporeal devices, multiple antiplatelet and anticoagulation strategies - including unfractionated heparin, low-molecular-weight heparin, citrate, direct thrombin inhibitors, and direct oral anticoagulants have been used to mitigate the thrombotic milieu within the patient and device. In the following manuscript, we outline the current data on anticoagulation strategies for commonly used extracorporeal circulatory devices, highlighting the potential benefits and complications involved with each.
  • ||||||||||  dabigatran etexilate / Generic mfg.
    Clinical, Journal:  TEG-guided treatment of a dabigatran overdose in a patient with acute kidney failure (Pubmed Central) -  Jul 28, 2021   
    As dabigatran plasma level testing was not available and conventional coagulation analysis was out of interpretable range due to the impact of dabigatran, continuous thrombelastography (TEG) was used to detect the effect of dabigatran and monitor the treatment results. The most significant parameter used in the kaolin activated clotting time was the R‑time parameter, which was massively prolonged by the interrupted coagulation cascade.
  • ||||||||||  Journal:  Structural and functional analysis of the simultaneous binding of two duplex/quadruplex aptamers to human α-thrombin. (Pubmed Central) -  Jul 24, 2021   
    In particular, the binding of an aptamer to its exosite reduces the intrinsic flexibility of the other exosite, that preferentially assumes conformations similar to those observed in the bound state, suggesting a predisposition to interact with the other aptamer. This behaviour is reflected in a significant increase of the anticoagulant activity of NU172 when the inactive HD22_27mer is bound to exosite II, providing a clear evidence of the synergic action of the two aptamers.
  • ||||||||||  dabigatran etexilate / Generic mfg.
    Preclinical, Journal:  Local blood coagulation drives cancer cell arrest and brain metastasis in a mouse model. (Pubmed Central) -  Jul 23, 2021   
    Thrombin inhibition by treatment with low molecular weight heparin or dabigatran and an anti-VWF antibody prevented clot formation, cancer cell arrest, extravasation, and the formation of brain macrometastases...In conclusion, our data shows that plasmatic coagulation is activated early by intravascular tumor cells in the brain, with subsequent clot formation, discovering a novel and specific mechanism that is crucial for brain colonization. Direct or indirect thrombin and VWF inhibitors emerge as promising drug candidates for BM prevention trials.
  • ||||||||||  Journal:  Potent trivalent inhibitors of thrombin through hybridization of salivary sulfopeptides from hematophagous arthropods. (Pubmed Central) -  Jul 22, 2021   
    A lead hybrid inhibitor possessed potent anticoagulant activity, blockade of both thrombin generation and platelet aggregation in vitro and efficacy in a murine thrombosis model at 1 mg kg -1 . The rational engineering approach described here lays the foundation for the development of potent and selective inhibitors for a range of other enzymatic targets that possess multiple sites for the disruption of protein-protein interactions, in addition to an active site.
  • ||||||||||  bivalirudin / Generic mfg.
    Clinical, Journal:  Extracorporeal Membrane Oxygenation Complications in Heparin- and Bivalirudin-Treated Patients. (Pubmed Central) -  Jul 20, 2021   
    The rational engineering approach described here lays the foundation for the development of potent and selective inhibitors for a range of other enzymatic targets that possess multiple sites for the disruption of protein-protein interactions, in addition to an active site. Our results confirm the safety and efficacy of bivalirudin as an alternative anticoagulant in extracorporeal membrane oxygenation and suggest a potential benefit in less blood product transfusion, although prospective studies are needed to evaluate the true effect of bivalirudin versus the disease processes that prompted its use in our study population.
  • ||||||||||  fondaparinux / Generic mfg.
    Review, Journal:  Spontaneous HIT syndrome: Knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia. (Pubmed Central) -  Jul 17, 2021   
    However, certain non-heparin medications (pentosan polysulfate, hypersulfated chondroitin sulfate, fondaparinux) can trigger "HIT"...The emerging concept is that classic HIT reflects platelet-activating anti-PF4/heparin antibodies whereas spontaneous HIT syndrome and other atypical "autoimmune HIT" presentations (delayed-onset HIT, persisting HIT, heparin "flush" HIT) reflect heparin-independent platelet-activating anti-PF4 antibodies-although the precise relationships between PF4 epitope targets and the clinical syndromes remain to be determined. Treatment of spontaneous HIT syndrome includes non-heparin anticoagulation (direct oral Xa inhibitors favored over direct thrombin inhibitors) and high-dose immunoglobulin.
  • ||||||||||  bivalirudin / Generic mfg., argatroban / Generic mfg.
    Journal:  Argatroban Versus Bivalirudin in the Treatment of Suspected or Confirmed Heparin-Induced Thrombocytopenia. (Pubmed Central) -  Jul 7, 2021   
    Average time to initial therapeutic anticoagulation was 4.71 hours and 9.8 hours for the argatroban and bivalirudin groups, respectively (P < .01). Argatroban may be advantageous compared to bivalirudin in achieving initial therapeutic anticoagulation goals among patients with suspected or confirmed HIT.
  • ||||||||||  bivalirudin / Generic mfg.
    Clinical, Journal:  Time in Therapeutic Range for Bivalirudin Among Pediatric Ventricular Assist Device Recipients. (Pubmed Central) -  Jul 7, 2021   
    Because %TTR reflects the degree of safety and efficacy in chronic anticoagulation, this relatively high %TTR among a diverse, often critically ill cohort suggests that bivalirudin may be a promising agent. Although this study was underpowered to comprehensively evaluate adverse events on bivalirudin, this represents an important next step for larger scale study.
  • ||||||||||  Journal:  Thrombin alters the synthesis and processing of CYR61/CCN1 in human corneal stromal fibroblasts and myofibroblasts through multiple distinct mechanisms. (Pubmed Central) -  Jul 4, 2021   
    In cultured human corneal stromal fibroblasts and myofibroblasts, thrombin regulates Cyr61 through two mechanisms: 1) thrombin increases the Cyr61 expression at the message and protein levels, and 2) thrombin increases the activation of a leupeptin-sensitive protease that stimulates the cleavage of Cyr61 into N- and C-terminal domain populations in or near the thrombospondin type-1 domain. Generation of Cyr61 peptides during corneal injury stimulation may reveal additional functions of the protein, which modulate corneal wound healing activities or decrease activities of the full-length Cyr61 form.
  • ||||||||||  dabigatran etexilate / Generic mfg.
    Preclinical, Journal:  Multimodal imaging of bacterial-host interface in mice and piglets with Staphylococcus aureus endocarditis. (Pubmed Central) -  Jun 24, 2021   
    The imaging agents, based on the clinical thrombin inhibitor dabigatran, are bound to heart valve vegetations in mice...Aortic or tricuspid S. aureus endocarditis in piglets was also successfully imaged with clinical PET/magnetic resonance imaging. Our data map a route toward adjuvant immunotherapy for endocarditis and provide efficient tools to monitor this drug class for infectious diseases.