Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(argatroban). Showing records 1 – 3 of 3 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


McMaster University

1. Yeh, Calvin Hsiung. FUNCTIONAL STUDIES WITH DIRECT ORAL ANTICOAGULANTS: INVESTIGATION OF THE REGULATION OF KEY BLOOD COAGULATION PROTEASES.

Degree: PhD, 2016, McMaster University

Intrinsic structural and conformational mechanisms regulate the functional specificity of the coagulation system. The study of these structure-function relationships is important for understanding the strategies used in the management of clinical thrombosis. Previous studies have shown that the central enzyme in clotting, thrombin, is sequestered inside of a clot, and protected from the natural downregulator antithrombin (AT). This is problematic for anticoagulants like heparin which depend on AT. Subsequently, it was found that the key upstream propagator of thrombin, the prothrombinase enzyme complex, is also resistant to the AT-heparin. Our data show that further upstream of prothrombinase, the intrinsic tenase is only moderately protected, while there is no protection at the level of the initiator complex, extrinsic tenase. This protection phenomenon possibly reflects steric and allosteric mechanisms that ensure maximal activation of the coagulation system once a threshold stimulus is achieved. These mechanisms likely evolved as a result of conformational rearrangement, as evidenced by the proteolytic activation of thrombin activity following proteolysis of prothrombin. Indeed, subtle differences in the structural interaction of ligands with the active site can lead to substantial differences in enzyme activity. The binding of rivaroxaban and apixaban to factor Xa is nearly identical; both interact with the active site with comparable affinity. Despite this, a 3-fold faster rate of the rivaroxaban on-rate yields significantly greater prolongation of the prothrombin time (PT) and activated partial thromboplastin time (aPTT), global tests of coagulation. These small differences in ligand interaction also have allosteric consequences. Structural differences between the direct thrombin inhibitors dabigatran and argatroban yield divergent exosite-mediated thrombin binding to physiologic ligands like yA-fibrin, y'-fibrin, factor Va, and factor VIII, interactions that govern clot-mediated protection from AT inhibition, and the various functions of thrombin. These divergent effects were robust and ligand-dependent, suggesting conserved energetic scaffolds within the thrombin molecule that govern allosteric changes throughout the molecule. Because proteolysis of prothrombin yields significant allosteric and structural rearrangement that capacitates the active site for substrate recognition amd catalytic ability, we investigated the role of Ser195, a key residue in the thrombin catalytic triad in also regulating thrombin allostery. Site directed mutagenesis of Ser195 to Ala yielded a significant increase in the flexibility of the entire thrombin molecule, as evidenced by increased potency of dabigatran and argatroban in terms of their capacity to modulate exosite binding through the active site, and increased interexosite cooperative and competitive allostery. Together, these studies represent an advance in our understanding of the consequences of both small molecule ligation of coagulation proteases, as well as the… Advisors/Committee Members: Weitz, Jeffrey I., Biochemistry and Biomedical Sciences.

Subjects/Keywords: Coagulation; Proteases; Enzyme kinetics; Direct oral inhibitors; Dabigatran; Argatroban; Thrombin; Heparin; Factor Xa; Prothrombinase

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Yeh, C. H. (2016). FUNCTIONAL STUDIES WITH DIRECT ORAL ANTICOAGULANTS: INVESTIGATION OF THE REGULATION OF KEY BLOOD COAGULATION PROTEASES. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/19502

Chicago Manual of Style (16th Edition):

Yeh, Calvin Hsiung. “FUNCTIONAL STUDIES WITH DIRECT ORAL ANTICOAGULANTS: INVESTIGATION OF THE REGULATION OF KEY BLOOD COAGULATION PROTEASES.” 2016. Doctoral Dissertation, McMaster University. Accessed February 25, 2021. http://hdl.handle.net/11375/19502.

MLA Handbook (7th Edition):

Yeh, Calvin Hsiung. “FUNCTIONAL STUDIES WITH DIRECT ORAL ANTICOAGULANTS: INVESTIGATION OF THE REGULATION OF KEY BLOOD COAGULATION PROTEASES.” 2016. Web. 25 Feb 2021.

Vancouver:

Yeh CH. FUNCTIONAL STUDIES WITH DIRECT ORAL ANTICOAGULANTS: INVESTIGATION OF THE REGULATION OF KEY BLOOD COAGULATION PROTEASES. [Internet] [Doctoral dissertation]. McMaster University; 2016. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/11375/19502.

Council of Science Editors:

Yeh CH. FUNCTIONAL STUDIES WITH DIRECT ORAL ANTICOAGULANTS: INVESTIGATION OF THE REGULATION OF KEY BLOOD COAGULATION PROTEASES. [Doctoral Dissertation]. McMaster University; 2016. Available from: http://hdl.handle.net/11375/19502


University of Illinois – Chicago

2. Patel, Vardhaman. Direct Thrombin Inhibitors: Use and Consequences in Patients with Heparin-Induced Thrombocytopenia.

Degree: 2015, University of Illinois – Chicago

Heparin-induced thrombocytopenia (HIT) is an immunologic response to heparin exposure that may lead to thrombosis. Argatroban and bivalirudin are two commonly used direct thrombin inhibitors (DTIs) for the prevention of thrombosis in patients with HIT. However, DTIs may lead to major bleeding events. Data on the use and consequences of DTIs is limited. Of note, patients with suspected HIT are of interest in the thesis, as current guidelines recommend the initiation of DTI treatment at the time of clinical suspicion of HIT. This thesis focused on the identification of suspected HIT, and the use and consequences of direct thrombin inhibitors (DTI) for the treatment of suspected HIT. First, algorithms based on diagnostic codes, medications and diagnostic tests were developed and validated to identify patients with suspected HIT. An algorithm based only on the timing of medication and diagnostic tests was recommended for the identification of suspected HIT from claims data, as it was observed to have the highest positive predictive value and sensitivity. Second, the rates of thrombosis, major bleeding, amputation and mortality were compared between argatroban-treated and bivalirudin-treated patients using administrative claims data obtained from the University HealthSystem Consortium. The difference in the likelihood of thrombosis, amputation and mortality between the two DTI groups was not statistically significant. However, bivalirudin-treated patients were more likely to experience major bleeding than argatroban-treated patients. Third, the use of bivalirudin for the treatment of suspected HIT (off-label use) increased from one-third to half of DTI-treated patients from 2010 to 2012. Patients treated by surgeons or specialists were more likely to receive off-label bivalirudin compared to patients treated by primary care. In addition, hepatic impairment and skin infection increased the odds of patients to receive bivalirudin over argatroban. In conclusion, the off-label use of bivalirudin should be scrutinized for medical necessity due to the higher risk of bleeding than argatroban, except in patients with hepatic impairment. Advisors/Committee Members: Walton, Surrey M. (advisor), Schumock, Glen T. (committee member), Lee, Todd A. (committee member), Galanter, William L. (committee member), Nutescu, Edith A. (committee member), Hohmann, Samuel F. (committee member).

Subjects/Keywords: 1; comparative effectiveness; 2; direct thrombin inhibitors; 3; argatroban; 4; bivalirudin; 5; thrombosis; 6; major bleeding; 7; safety; 8; off-label; 9; algorithms; 10; validity

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Patel, V. (2015). Direct Thrombin Inhibitors: Use and Consequences in Patients with Heparin-Induced Thrombocytopenia. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/19794

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Patel, Vardhaman. “Direct Thrombin Inhibitors: Use and Consequences in Patients with Heparin-Induced Thrombocytopenia.” 2015. Thesis, University of Illinois – Chicago. Accessed February 25, 2021. http://hdl.handle.net/10027/19794.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Patel, Vardhaman. “Direct Thrombin Inhibitors: Use and Consequences in Patients with Heparin-Induced Thrombocytopenia.” 2015. Web. 25 Feb 2021.

Vancouver:

Patel V. Direct Thrombin Inhibitors: Use and Consequences in Patients with Heparin-Induced Thrombocytopenia. [Internet] [Thesis]. University of Illinois – Chicago; 2015. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/10027/19794.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Patel V. Direct Thrombin Inhibitors: Use and Consequences in Patients with Heparin-Induced Thrombocytopenia. [Thesis]. University of Illinois – Chicago; 2015. Available from: http://hdl.handle.net/10027/19794

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Briem, Philipp. Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support.

Degree: 2018, Freie Universität Berlin

Background: Argatroban, a direct thrombin inhibitor, is considered an alternative to heparin for patients with heparin-induced thrombocytopenia. Knowledge on the use of argatroban in patients with acute respiratory distress syndrome (ARDS) undergoing extracorporeal membrane oxygenation is limited. Therefore, this study assessed the feasibility, efficacy and safety of argatroban in critically ill ARDS patients undergoing extracorporeal lung support. Methods: This retrospective analysis included ARDS patients on extracorporeal lung support who received argatroban between 2007 and 2014 in a single ARDS referral center. As controls, patients who received heparin were matched for age, sex, body mass index and severity of illness scores. Major and minor bleeding complications, thromboembolic events, administered number of erythrocyte concentrates, thrombocytes and fresh frozen plasmas were assessed. The number of extracorporeal circuit systems and extracorporeal lung support cannulas needed due to clotting or clogging was recorded. Also assessed was the efficacy to reach the targeted activated partial thromboplastin time (aPTT) in the first consecutive 14 days of therapy, and the controllability of aPTT values within a therapeutic range of 50-75 s. Mann Whitney-U tests, Friedman tests and multivariate non-parametric analyses for longitudinal data (MANOVA; Brunner´s analysis) were applied where appropriate. Results: Of the 535 patients who met the inclusion criteria, 39 receiving argatroban and 39 matched patients receiving heparin (controls) were included. Baseline characteristics were similar between the two groups, including severity of illness and organ failure scores. There were no significant differences in major and minor bleeding complications. Rates of thromboembolic events were generally low and were similar between the two groups, as were the rates of transfusions required and device-associated complications. The controllability of both argatroban and heparin improved over time, with a significantly increasing probability to reach the targeted aPTT corridor over the first days (p<0.001). Over time, there were significantly fewer aPTT values below the targeted aPTT goal in the argatroban group than in the heparin group (p<0.05). Both argatroban and heparin reached therapeutic aPTT values for adequate application of extracorporeal lung support. Conclusions: Argatroban appears to be a feasible, effective and safe anticoagulant for critically ill ARDS patients undergoing extracorporeal lung support. Advisors/Committee Members: male (gender), N.N. (firstReferee), N.N. (furtherReferee).

Subjects/Keywords: efficacy; argatroban; heparin; safety; ards; ecmo; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

…verbesserte sich die Kontrollierbarkeit von Argatroban und Heparin signifikant im Zeitverlauf und… …x28;p < 0,001). In der Argatroban-Gruppe wurden im Zeitverlauf signifikant weniger… …Argatroban als auch Heparin ermöglicht therapeutische aPTT-Werte, die für eine suffiziente ECMO… …Therapie benötigt werden. Schlussfolgerung Argatroban scheint ein gut steuerbares, effektives… …Lungenunterstützung zu sein. 5 Abstract Abstract Background Argatroban, a direct thrombin inhibitor, is… 

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Briem, P. (2018). Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-684

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Briem, Philipp. “Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support.” 2018. Thesis, Freie Universität Berlin. Accessed February 25, 2021. http://dx.doi.org/10.17169/refubium-684.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Briem, Philipp. “Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support.” 2018. Web. 25 Feb 2021.

Vancouver:

Briem P. Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support. [Internet] [Thesis]. Freie Universität Berlin; 2018. [cited 2021 Feb 25]. Available from: http://dx.doi.org/10.17169/refubium-684.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Briem P. Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support. [Thesis]. Freie Universität Berlin; 2018. Available from: http://dx.doi.org/10.17169/refubium-684

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.