Ph.D. Thesis Defense - Biomarkers of Coagulation and Fibrinolysis in Primary Graft Dysfunction in Lung Transplant Recipients
Date: May 14, 2008
Time: 3:00 PM
Location: Bossone Research Enterprise Center, Room: 302
Nancy A. Robinson
Advisor: Fred Allen, Ph.D.
Primary graft dysfunction (PGD) is a severe acute lung injury syndrome following lung transplantation. 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.
Recently, there has been increasing recognition that impaired fibrinolysis plays a role in pathogenesis of acute lung injury and that inherent donor and recipient characteristics may play an important role in determining risk of PGD; however, a lack of standardization as well as methodological issues significantly hampered early studies. As a result of inconsistencies in methods there has been insufficient evidence to make strong conclusions of association between PGD and many potential risk factors.
The focus of the research conducted for this thesis was the role of biomarkers in the coagulation and fibrinolytic pathways in the development of PGD in lung transplant recipients as well as the identification of potential clinical risk factors.
Plasma levels of Protein C and Plasminogen Activator Inhibitor “PAI-1” before lung transplantation and 6, 24, 48, and 72 h after allograft reperfusion was measured in 128 lung transplant recipients The primary outcome was PGD ISHLT Grade 3 beyond 72 hours postoperatively (PaO2/FiO2<200 with alveolar infiltrates). In addition, clinical risk factors/Biomarker profiles were evaluated using logistic regression models.
This research provided the first evidence that decreased levels of Protein-C and increased levels of Plasminogen Activator Inhibitor “PAI-1” in circulating plasma contribute to the development of PGD in lung transplant patients. In addition, this research provides evidence of the effect of donor and recipient risk factors as well as confounding variables on biomarker levels and the outcome, PGD. The goal of this research was to provide insight into the mechanisms of progression to PGD, aid in potential prediction of PGD based on donor and recipient characteristics, and to provide justification for novel therapeutics aimed at preventing PGD prior to full onset or death.
The Bossone Research Enterprise Center is located at the corner of 32nd and Market Streets.