subject:(bivalirudin)

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University of Arizona

1. Alouidor, Benjamin. Microfluidic Point-Of-Care Ecarin Based Assays for Monitoring Direct Thrombin Inhibitor Therapy .

Degree: 2018, University of Arizona

URL: http://hdl.handle.net/10150/628176

► Direct thrombin inhibitors (DTIs), such as dabigatran, have maintained steady outpatient use due to their high oral bioavailability and relatively safe “on-therapy” range. The creation… (more)

▼ Direct thrombin inhibitors (DTIs), such as dabigatran, have maintained steady outpatient use due to their high oral bioavailability and relatively safe “on-therapy” range. The creation of new intravenous antibody reversal agents, like Idarucizumab, have renewed DTI monitoring interests. Current clinical methods within the United States lack the capacity to quantify DTI concentrations across wide ranges. At present, the international gold standard in quantifying DTI therapeutic thresholds is the ecarin clotting time (ECT). The linear prolongation of the ECT is directly proportional to specific DTI concentrations and inversely proportional to absorbance. This work focused on the development of a microfluidic paper analytic device (µPAD) that can quantify DTI concentration within a patient’s whole blood sample. Capillary action propels a small blood sample to flow through the nitrocellulose paper channels. Digital images of sample migration are then automatically captured by our self-coded Raspberry Pi and/or the Samsung Galaxy S8 smartphone camera. Commercial wax printers were used to create these disposable low-cost µPAD chips. Both the flow length and the blue absorbance from the plasma front on the μPAD were measured, allowing simultaneous, dual assay of ecarin clotting test (ECT) and ecarin chromogenic assay (ECA). Statistically significant (p < 0.05) changes in flow and absorbance were observed within our translational research study. Currently there are no quantitative commercially available point of care (POC) tests for the ECT within the U.S. Implementation of the ECT will differentiate between true supratherapeutic incidents and limit the unwarranted use of reversal agents. Additionally, DTIs have proved useful in maintaining anticoagulation during mechanical circulatory support in heparin induced cytopenia (HIT) patients. Our hopes are that our device will provide caregivers and patients the tools to monitor DTI therapy within both in and/or outpatient settings. Advisors/Committee Members: Yoon, Jeong-Yeol (advisor), Wong, Raymond (advisor), Khalpey, Zain (committeemember).

Subjects/Keywords: anticoagulant; bivalirudin; dabigatran; direct thrombin inhibitor; ecarin; microfluidic

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

APA (6^th Edition):

Alouidor, B. (2018). Microfluidic Point-Of-Care Ecarin Based Assays for Monitoring Direct Thrombin Inhibitor Therapy . (Masters Thesis). University of Arizona. Retrieved from http://hdl.handle.net/10150/628176

Chicago Manual of Style (16^th Edition):

Alouidor, Benjamin. “Microfluidic Point-Of-Care Ecarin Based Assays for Monitoring Direct Thrombin Inhibitor Therapy .” 2018. Masters Thesis, University of Arizona. Accessed March 05, 2021. http://hdl.handle.net/10150/628176.

MLA Handbook (7^th Edition):

Alouidor, Benjamin. “Microfluidic Point-Of-Care Ecarin Based Assays for Monitoring Direct Thrombin Inhibitor Therapy .” 2018. Web. 05 Mar 2021.

Vancouver:

Alouidor B. Microfluidic Point-Of-Care Ecarin Based Assays for Monitoring Direct Thrombin Inhibitor Therapy . [Internet] [Masters thesis]. University of Arizona; 2018. [cited 2021 Mar 05]. Available from: http://hdl.handle.net/10150/628176.

Council of Science Editors:

Alouidor B. Microfluidic Point-Of-Care Ecarin Based Assays for Monitoring Direct Thrombin Inhibitor Therapy . [Masters Thesis]. University of Arizona; 2018. Available from: http://hdl.handle.net/10150/628176

Freie Universität Berlin

2. Pepke, Wojciech. The effect of antithrombotic medicaments on platelets function during and after percutaneus coronary intervention with stenting (PCI) an on tissue factor (TF) expression.

Degree: 2013, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-9630

► A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary… (more)

▼ A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary artery disease (CAD) leads to an improved outcome. Aim of the first study was to examine the periprocedural platelet reactivity after administrating bivalirudin during PCI compared to unfractionated heparin (UFH) administration. Further, the effect of bivalirudin on induced tissue factor (TF) expression in smooth muscle cells (SMC) was determined. TF is an Initiator of extrinsic coagulation pathway and is involved in formation of the thrombus under physiological and pathophysiological conditions. The aim of our second study was to examine the effects of PCI on TF expression in coronary arteries and on the circulating TF level in relation to the duration of clopidogrel treatment in a porcine model. How the differential TF isoform expression is regulated is still unknown. For that, we compared in our third study the impact of Phosphatidylinositol 3-Kinase/Protein Kinase B pathway inhibition on alternative splicing of TF in human endothel cells (HUVEC). Bivalirudin significantly diminished the agonist-induced platelet reactivity post-PCI. Compared to UFH treatment, the adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP)-induced thrombospondin expression post-PCI was reduced when bivalirudin was administrated during intervention. In contrast to UFH, bivalirudin reduced the P-selectin expression of unstimulated and ADP-induced platelets post-PCI. Moreover, bivalirudin inhibited the thrombin-, but not FVIIa- or FVIIa/FX- induced TF expression and pro-coagulant TF activity of SMC. In our porcine model we could show that prolonged clopidogrel treatment reduced coronary TF expression and tended to reduce the blood TF level post-PCI, thus possibly modulating the risk of late thrombosis. In a final step of our investigations we showed that the Phosphatidylinosito 3-Kinase/Protein Kinase B pathway modulates alternative splicing of TF in human endothel cells (HUVEC), distinct from transcriptional regulation. Advisors/Committee Members: [email protected] (contact), m (gender), Prof. Dr. med. U. Rauch-Kröhnert (firstReferee), Prof. Dr. med. H. Völler (furtherReferee), Priv.-Doz. Dr. med. C. Opitz (furtherReferee).

Subjects/Keywords: Platelets; Bivalirudin; Percutaneus Coronary Intervention (PCI); 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

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

APA (6^th Edition):

Pepke, W. (2013). The effect of antithrombotic medicaments on platelets function during and after percutaneus coronary intervention with stenting (PCI) an on tissue factor (TF) expression. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-9630

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

Chicago Manual of Style (16^th Edition):

Pepke, Wojciech. “The effect of antithrombotic medicaments on platelets function during and after percutaneus coronary intervention with stenting (PCI) an on tissue factor (TF) expression.” 2013. Thesis, Freie Universität Berlin. Accessed March 05, 2021. http://dx.doi.org/10.17169/refubium-9630.

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

MLA Handbook (7^th Edition):

Vancouver:

Pepke W. The effect of antithrombotic medicaments on platelets function during and after percutaneus coronary intervention with stenting (PCI) an on tissue factor (TF) expression. [Internet] [Thesis]. Freie Universität Berlin; 2013. [cited 2021 Mar 05]. Available from: http://dx.doi.org/10.17169/refubium-9630.

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

Council of Science Editors:

Pepke W. The effect of antithrombotic medicaments on platelets function during and after percutaneus coronary intervention with stenting (PCI) an on tissue factor (TF) expression. [Thesis]. Freie Universität Berlin; 2013. Available from: http://dx.doi.org/10.17169/refubium-9630

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

University of Lund

3. Koul, Sasha. Improving outcomes in patients with coronary heart disease using national registers and platelet function testing.

Degree: 2015, University of Lund

URL: https://lup.lub.lu.se/record/8084547 ; https://portal.research.lu.se/ws/files/3671633/8084558.pdf

► Introduction: Ischemic heart disease is the leading cause of death worldwide. The aims of this thesis were to evaluate different contemporary approaches in coronary care… (more)

▼ Introduction: Ischemic heart disease is the leading cause of death worldwide. The aims of this thesis were to evaluate different contemporary approaches in coronary care with regard to mortality and myocardial infarction. Methods: The thesis consists of 6 papers with 4 papers evaluating different exposures and their outcomes (clopidogrel pre-treatment, 5 different anti-platelet protocols, ticagrelor pre-treatment and treatment delays to PCI). Two papers involved evaluation of interventions: platelet function testing in patients with clopidogrel and clinical evaluation of bivalirudin versus heparin in patients with acute coronary syndromes, respectively. Patients with ischemic heart disease were identified using national and local registers. All patients in the six included papers were treated with PCI. Results: Pre-treatment with clopidogrel prior to primary PCI was associated with improved cardiovascular outcomes compared to peri-procedural clopidogrel. The composite end point of one-year mortality and MI was improved as well as mortality alone. Pre-treatement with ticagrelor compared to peri-procedural ticagrelor did not affect 30-day mortality. In one of three statistical models, 30-day myocardial infarction was reduced with ticagrelor pre-treatment. Platelet function testing failed to identify a clinically applicable cut-off value to predict stent thrombosis or new onset MI in patients with dual anti-platelet therapy. Using platelet function testing, a loading dose of either prasugrel or ticagrelor on top of a previous loading dose of clopidogrel, did not cause a pharmacodynamic overshoot of platelet inhibition. Treatment delays from first medical contact to PCI exceeding one hour were associated with higher mortality in patients with STEMI undergoing primary PCI. Finally, we showed that a register based randomized clinical trial designed to evaluate bivalirudin versus heparin in patients with ACS and PCI is feasible, with a higher degree of enrollment of “real-life” patients than in in conventional randomized clinical trials. Conclusions: This thesis has potential implications for acute care of patients with myocardial infarction.

Subjects/Keywords: Cardiac and Cardiovascular Systems; STEMI; NSTEMI; ACS; Ticagrelor; clopidogrel; prasugrel; treatment delays; bivalirudin; heparin; platelet function testing

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

APA (6^th Edition):

Koul, S. (2015). Improving outcomes in patients with coronary heart disease using national registers and platelet function testing. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/8084547 ; https://portal.research.lu.se/ws/files/3671633/8084558.pdf

Chicago Manual of Style (16^th Edition):

Koul, Sasha. “Improving outcomes in patients with coronary heart disease using national registers and platelet function testing.” 2015. Doctoral Dissertation, University of Lund. Accessed March 05, 2021. https://lup.lub.lu.se/record/8084547 ; https://portal.research.lu.se/ws/files/3671633/8084558.pdf.

MLA Handbook (7^th Edition):

Koul, Sasha. “Improving outcomes in patients with coronary heart disease using national registers and platelet function testing.” 2015. Web. 05 Mar 2021.

Vancouver:

Koul S. Improving outcomes in patients with coronary heart disease using national registers and platelet function testing. [Internet] [Doctoral dissertation]. University of Lund; 2015. [cited 2021 Mar 05]. Available from: https://lup.lub.lu.se/record/8084547 ; https://portal.research.lu.se/ws/files/3671633/8084558.pdf.

Council of Science Editors:

Koul S. Improving outcomes in patients with coronary heart disease using national registers and platelet function testing. [Doctoral Dissertation]. University of Lund; 2015. Available from: https://lup.lub.lu.se/record/8084547 ; https://portal.research.lu.se/ws/files/3671633/8084558.pdf

University of Illinois – Chicago

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

Degree: 2015, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/19794

► 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… (more)

▼ 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

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

APA (6^th 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 (16^th Edition):

Patel, Vardhaman. “Direct Thrombin Inhibitors: Use and Consequences in Patients with Heparin-Induced Thrombocytopenia.” 2015. Thesis, University of Illinois – Chicago. Accessed March 05, 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 (7^th Edition):

Patel, Vardhaman. “Direct Thrombin Inhibitors: Use and Consequences in Patients with Heparin-Induced Thrombocytopenia.” 2015. Web. 05 Mar 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 Mar 05]. 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

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