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Dissertation
Biomarkers of coagulation and fibrinolysis in primary graft dysfunction in lung transplant recipients
Doctor of Philosophy (Ph.D.), Drexel University
May 2008
DOI:
https://doi.org/10.17918/etd-2812
Abstract
Primary graft dysfunction (PGD) is a severe acute lung injury syndrome following lung transplantation.1-3 In the lung transplant clinical and research community, PGD has received much attention as a leading cause of morbidity and mortality and is the primary cause of almost half of lung transplant deaths in the first 30 days. There has been increasing recognition that impaired fibrinolysis plays a role in pathogenesis of acute lung injury. Furthermore, inherent donor and recipient characteristics may play an important role in determining risk of PGD in laboratory models and clinical studies, suggesting that this variation may partially be due to differing susceptibility to lung injury in recipients and donors. The focus of this thesis was the role of biomarkers in the coagulation and fibrinolytic pathways in the development of PGD in human lung transplant recipients. Plasma levels of Protein C and Plasminogen Activator Inhibitor "PAI-1" pre-transplant, immediate post-transplant, 24, 48, and 72 hours post-transplant were measured in 131 lung transplant recipients. The primary outcome was PGD, defined as International Society of Heart and Lung Transplantation (ISHLT) Working Group definition of PGD, Grade 3. Potential confounding effects of clinical variables were also evaluated using logistic regression models.15% of subjects were identified as PGD, Grade 3. Lower levels of Protein C and higher levels of PAI -1 were associated with the PGD cases. Recipient's diagnosis and procedure type as well as the administration of blood products within 24 hours post transplant and Pulmonary Arterial Systolic Pressure (PASP) were all determined to be statistically different between the PGD and Non-PGD groups. The association of both, Protein C and PAI-1, with PGD were independent of all potential confounders. This research provides evidence that decreased levels of Protein-C and increased levels of PAI-1 in circulating plasma contribute to the development of PGD in lung transplant patients. The goal of this research was to present insight into the mechanisms of progression to PGD, to aid in potential prediction of PGD, and to put forward justification for novel therapeutics (Protein C), aimed at preventing PGD prior to full onset or death.
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Details
- Title
- Biomarkers of coagulation and fibrinolysis in primary graft dysfunction in lung transplant recipients
- Creators
- Nancy Robinson - DU
- Contributors
- Fred D. Allen Jr. (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 2812; 991014632197604721