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Transport and biorheological effects...

University of Pennsylvania., Chemical and Biomolecular Engineering.

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Transport and biorheological effects in human coagulation.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Transport and biorheological effects in human coagulation./
Author:	Colace, Thomas Vincent, III.
Description:	217 p.
Notes:	Source: Dissertation Abstracts International, Volume: 74-10(E), Section: B.
Contained By:	Dissertation Abstracts International74-10B(E).
Subject:	Biology, Physiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3565042
ISBN:	9781303145421

Transport and biorheological effects in human coagulation.
Colace, Thomas Vincent, III.

Transport and biorheological effects in human coagulation. - 217 p.

Source: Dissertation Abstracts International, Volume: 74-10(E), Section: B.

Thesis (Ph.D.)--University of Pennsylvania, 2013.

To date, microfluidic techniques provide the most physiologically relevant environment for the study of hemostasis and thrombosis using human whole blood. This thesis describes the use of a variety of microfluidic geometries, flow conditions, patterned surfaces of procoagulant proteins, and pharmacological agents to investigate the role of hemodynamics at multiple length scales. We have demonstrated a novel method to assess the size of platelet aggregates depositing on collagen type I surfaces and described the local wall shear rate dependence of their shape. We have phenotyped individual donor platelet responses to a procoagulant collagen surface under a variety of pharmacological agents and identified a single donor with insensitivity to aspirin explained by a thromboxane receptor mutation. We have developed a technique to initiate clotting on collagen and immobilized tissue factor and studied the role of thrombin in platelet aggregation as it pertains to platelet activation and fibrin mediated stabilization of the thrombus. We utilized a microfluidic model of coronary stenosis to visualize for the first time the aggregation of von Willebrand factor, a large multimeric protein involved in high shear platelet capture, into long (>100 mum) fibers on collagen surfaces. We demonstrated that these fibers may be responsible for an unrecognized mode of platelet capture that results in rapidly forming aggregates that have a propensity to embolize. Lastly we describe an ongoing effort to develop a new model of thrombosis under flow which relies on the intrinsic pathway of coagulation as a triggering mechanism. The development of new microfluidic models of hemostasis and thrombosis has been essential to advancing our knowledge of the biology underlying myocardial infarction and stroke. In the future it will continue to provide new insights so that we may better identify new drug targets, design therapies, and develop diagnostic tests.

ISBN: 9781303145421Subjects--Topical Terms:

1017816
Biology, Physiology.

Transport and biorheological effects in human coagulation.
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100 1 $a Colace, Thomas Vincent, III. $3 2101615
245 1 0 $a Transport and biorheological effects in human coagulation.
300 $a 217 p.
500 $a Source: Dissertation Abstracts International, Volume: 74-10(E), Section: B.
500 $a Adviser: Scott L. Diamond.
502 $a Thesis (Ph.D.)--University of Pennsylvania, 2013.
520 $a To date, microfluidic techniques provide the most physiologically relevant environment for the study of hemostasis and thrombosis using human whole blood. This thesis describes the use of a variety of microfluidic geometries, flow conditions, patterned surfaces of procoagulant proteins, and pharmacological agents to investigate the role of hemodynamics at multiple length scales. We have demonstrated a novel method to assess the size of platelet aggregates depositing on collagen type I surfaces and described the local wall shear rate dependence of their shape. We have phenotyped individual donor platelet responses to a procoagulant collagen surface under a variety of pharmacological agents and identified a single donor with insensitivity to aspirin explained by a thromboxane receptor mutation. We have developed a technique to initiate clotting on collagen and immobilized tissue factor and studied the role of thrombin in platelet aggregation as it pertains to platelet activation and fibrin mediated stabilization of the thrombus. We utilized a microfluidic model of coronary stenosis to visualize for the first time the aggregation of von Willebrand factor, a large multimeric protein involved in high shear platelet capture, into long (>100 mum) fibers on collagen surfaces. We demonstrated that these fibers may be responsible for an unrecognized mode of platelet capture that results in rapidly forming aggregates that have a propensity to embolize. Lastly we describe an ongoing effort to develop a new model of thrombosis under flow which relies on the intrinsic pathway of coagulation as a triggering mechanism. The development of new microfluidic models of hemostasis and thrombosis has been essential to advancing our knowledge of the biology underlying myocardial infarction and stroke. In the future it will continue to provide new insights so that we may better identify new drug targets, design therapies, and develop diagnostic tests.
590 $a School code: 0175.
650 4 $a Biology, Physiology. $3 1017816
650 4 $a Engineering, Chemical. $3 1018531
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690 $a 0542
710 2 $a University of Pennsylvania. $b Chemical and Biomolecular Engineering. $3 2101616
773 0 $t Dissertation Abstracts International $g 74-10B(E).
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792 $a 2013
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3565042