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From Principle to Practice: Bridging the Gap in Patient Profiling

The standard clinical coagulation assays, activated partial thromboplastin time (aPTT) and prothrombin time (PT) cannot predict thrombotic or bleeding risk. Since thrombin generation is central to haemorrhage control and when unregulated, is the likely cause of thrombosis, thrombin generation assays...

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Autores principales: Foley, Jonathan H., Orfeo, Thomas, Undas, Anetta, McLean, Kelley C., Bernstein, Ira M., Rivard, Georges-Etienne, Mann, Kenneth G., Everse, Stephen J., Brummel-Ziedins, Kathleen E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556038/
https://www.ncbi.nlm.nih.gov/pubmed/23372761
http://dx.doi.org/10.1371/journal.pone.0054728
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author Foley, Jonathan H.
Orfeo, Thomas
Undas, Anetta
McLean, Kelley C.
Bernstein, Ira M.
Rivard, Georges-Etienne
Mann, Kenneth G.
Everse, Stephen J.
Brummel-Ziedins, Kathleen E.
author_facet Foley, Jonathan H.
Orfeo, Thomas
Undas, Anetta
McLean, Kelley C.
Bernstein, Ira M.
Rivard, Georges-Etienne
Mann, Kenneth G.
Everse, Stephen J.
Brummel-Ziedins, Kathleen E.
author_sort Foley, Jonathan H.
collection PubMed
description The standard clinical coagulation assays, activated partial thromboplastin time (aPTT) and prothrombin time (PT) cannot predict thrombotic or bleeding risk. Since thrombin generation is central to haemorrhage control and when unregulated, is the likely cause of thrombosis, thrombin generation assays (TGA) have gained acceptance as “global assays” of haemostasis. These assays generate an enormous amount of data including four key thrombin parameters (lag time, maximum rate, peak and total thrombin) that may change to varying degrees over time in longitudinal studies. Currently, each thrombin parameter is averaged and presented individually in a table, bar graph or box plot; no method exists to visualize comprehensive thrombin generation data over time. To address this need, we have created a method that visualizes all four thrombin parameters simultaneously and can be animated to evaluate how thrombin generation changes over time. This method uses all thrombin parameters to intrinsically rank individuals based on their haemostatic status. The thrombin generation parameters can be derived empirically using TGA or simulated using computational models (CM). To establish the utility and diverse applicability of our method we demonstrate how warfarin therapy (CM), factor VIII prophylaxis for haemophilia A (CM), and pregnancy (TGA) affects thrombin generation over time. The method is especially suited to evaluate an individual's thrombotic and bleeding risk during “normal” processes (e.g pregnancy or aging) or during therapeutic challenges to the haemostatic system. Ultimately, our method is designed to visualize individualized patient profiles which are becoming evermore important as personalized medicine strategies become routine clinical practice.
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spelling pubmed-35560382013-01-31 From Principle to Practice: Bridging the Gap in Patient Profiling Foley, Jonathan H. Orfeo, Thomas Undas, Anetta McLean, Kelley C. Bernstein, Ira M. Rivard, Georges-Etienne Mann, Kenneth G. Everse, Stephen J. Brummel-Ziedins, Kathleen E. PLoS One Research Article The standard clinical coagulation assays, activated partial thromboplastin time (aPTT) and prothrombin time (PT) cannot predict thrombotic or bleeding risk. Since thrombin generation is central to haemorrhage control and when unregulated, is the likely cause of thrombosis, thrombin generation assays (TGA) have gained acceptance as “global assays” of haemostasis. These assays generate an enormous amount of data including four key thrombin parameters (lag time, maximum rate, peak and total thrombin) that may change to varying degrees over time in longitudinal studies. Currently, each thrombin parameter is averaged and presented individually in a table, bar graph or box plot; no method exists to visualize comprehensive thrombin generation data over time. To address this need, we have created a method that visualizes all four thrombin parameters simultaneously and can be animated to evaluate how thrombin generation changes over time. This method uses all thrombin parameters to intrinsically rank individuals based on their haemostatic status. The thrombin generation parameters can be derived empirically using TGA or simulated using computational models (CM). To establish the utility and diverse applicability of our method we demonstrate how warfarin therapy (CM), factor VIII prophylaxis for haemophilia A (CM), and pregnancy (TGA) affects thrombin generation over time. The method is especially suited to evaluate an individual's thrombotic and bleeding risk during “normal” processes (e.g pregnancy or aging) or during therapeutic challenges to the haemostatic system. Ultimately, our method is designed to visualize individualized patient profiles which are becoming evermore important as personalized medicine strategies become routine clinical practice. Public Library of Science 2013-01-25 /pmc/articles/PMC3556038/ /pubmed/23372761 http://dx.doi.org/10.1371/journal.pone.0054728 Text en © 2013 Foley et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Foley, Jonathan H.
Orfeo, Thomas
Undas, Anetta
McLean, Kelley C.
Bernstein, Ira M.
Rivard, Georges-Etienne
Mann, Kenneth G.
Everse, Stephen J.
Brummel-Ziedins, Kathleen E.
From Principle to Practice: Bridging the Gap in Patient Profiling
title From Principle to Practice: Bridging the Gap in Patient Profiling
title_full From Principle to Practice: Bridging the Gap in Patient Profiling
title_fullStr From Principle to Practice: Bridging the Gap in Patient Profiling
title_full_unstemmed From Principle to Practice: Bridging the Gap in Patient Profiling
title_short From Principle to Practice: Bridging the Gap in Patient Profiling
title_sort from principle to practice: bridging the gap in patient profiling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556038/
https://www.ncbi.nlm.nih.gov/pubmed/23372761
http://dx.doi.org/10.1371/journal.pone.0054728
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