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You searched for +publisher:"University of North Carolina" +contributor:("Machlus, Kellie R."). One record found.

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University of North Carolina

1. Machlus, Kellie R. Pathophysiology of plasma hypercoagulability in thrombosis.

Degree: Pathology and Laboratory Medicine, 2011, University of North Carolina

Blood coagulation abnormalities are the leading cause of death world-wide. Elevated procoagulant factor levels (hypercoagulability) have been correlated with increased thrombin generation and increased risk of arterial and venous thrombosis. This dissertation explores the role of hypercoagulability on various aspects of coagulation and thrombosis in vitro and in vivo. Thrombin generation tests are increasingly being employed as a high throughput, global measure of procoagulant activity. Thrombin generation was measured using calibrated automated thrombography (CAT) in platelet-free plasma (PFP) and platelet-rich plasma (PRP). The relative sensitivity of CAT parameters to elevated factors XI, IX, VIII, X, and prothrombin was: PFP initiated with 1 pM tissue factor (TF) > PFP initiated with 5 pM TF > PRP initiated with 1 pM TF. Monitoring the peak height following initiation with 1 pM TF in PFP was most likely to detect hypercoagulability (increased procoagulant factors). Epidemiologic studies have correlated elevated plasma fibrinogen (hyperfibrinogenemia) with risk of arterial and venous thrombosis. However, it is unknown whether hyperfibrinogenemia is a biomarker of disease or causative in the etiology. In mice, hyperfibrinogenemia significantly shortened the time to occlusion (TTO) after FeCl3 injury to the saphenous vein and carotid artery. Hyperfibrinogenemia increased thrombus fibrin content, promoted faster fibrin formation, and increased fibrin network density, strength, and stability and increased thrombus thrombolysis resistance in vivo. These data indicate hyperfibrinogenemia directly promotes thrombosis and thrombolysis resistance via enhanced fibrin formation and stability. Studies have correlated elevated plasma factor VIII (FVIII) with thrombosis. However, like hyperfibrinogenemia, it is unclear whether elevated FVIII is a biomarker or causative agent. In mice, elevated FVIII had no effect on 3-minute FeCl3 carotid artery injury, but shortened the TTO after 2-minute injury. Additionally, elevated FVIII increased circulating thrombin-antithrombin complexes and stabilized clots after 2- but not 3-minute FeCl3 injury. In vitro, elevated FVIII increased thrombin generation and accelerated platelet aggregation only when initiated by low TF. These results demonstrate dependence of FVIII thrombogenicity on extent of vascular injury. These findings provide a better understanding of how plasma hypercoagulability impacts thrombogenesis. Specifically, these data suggest causative yet differential roles for hyperfibrinogenemia and elevated FVIII in thrombosis. Advisors/Committee Members: Machlus, Kellie R., Wolberg, Alisa.

Subjects/Keywords: School of Medicine; Department of Pathology and Laboratory Medicine

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

APA (6th Edition):

Machlus, K. R. (2011). Pathophysiology of plasma hypercoagulability in thrombosis. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:467a5300-943d-418b-9bb9-f72db83251c8

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):

Machlus, Kellie R. “Pathophysiology of plasma hypercoagulability in thrombosis.” 2011. Thesis, University of North Carolina. Accessed January 22, 2021. https://cdr.lib.unc.edu/record/uuid:467a5300-943d-418b-9bb9-f72db83251c8.

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

MLA Handbook (7th Edition):

Machlus, Kellie R. “Pathophysiology of plasma hypercoagulability in thrombosis.” 2011. Web. 22 Jan 2021.

Vancouver:

Machlus KR. Pathophysiology of plasma hypercoagulability in thrombosis. [Internet] [Thesis]. University of North Carolina; 2011. [cited 2021 Jan 22]. Available from: https://cdr.lib.unc.edu/record/uuid:467a5300-943d-418b-9bb9-f72db83251c8.

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

Council of Science Editors:

Machlus KR. Pathophysiology of plasma hypercoagulability in thrombosis. [Thesis]. University of North Carolina; 2011. Available from: https://cdr.lib.unc.edu/record/uuid:467a5300-943d-418b-9bb9-f72db83251c8

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

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