Published ahead of print on October 5, 2006, doi:10.1164/rccm.200606-827OC Am. J. Respir. Crit. Care Med., Volume 175, Number 1, January 2007, 69-74 A more recent version of this article appeared on January 1, 2007
Submitted on June 21, 2006 Association of Protein C and Type-1 Plasminogen Activator Inhibitor with Primary Graft DysfunctionJason D Christie1*,1 Division of Pulmonary, Allergy and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 2 Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 3 Division of Pulmonary, Allergy and Critical Care Medicine, Vanderbilt University, Nashville, TN, USA, 4 Division of Pulmonary, Allergy and Critical Care Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 5 Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA, 6 Division of Pulmonary, Allergy and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA, 7 Division of Pulmonary, Allergy and Critical Care Medicine, Johns Hopkins University Hospital, Baltimore, MD, USA, 8 Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA, 9 Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA; Department of Epidemiology, Columbia University, Mailman School of Public Health, New York, NY, USA * To whom correspondence should be addressed. E-mail: jchristi{at}cceb.med.upenn.edu.
Background: Acute lung injury is characterized by hypercoagulability and impaired fibrinolysis. We hypothesized that lower protein C and higher type-1 plasminogen activator inhibitor (PAI-1) levels in plasma would be associated with primary graft dysfunction (PGD) after lung transplantation. Design: Prospective, multicenter cohort study. Methods: We measured plasma levels of protein C and PAI-1 before lung transplantation and at 6, 24, 48, and 72 hours following allograft reperfusion in 128 lung transplant recipients at six centers. The primary outcome was Grade 3 PGD (PaO2/FiO2<200 with alveolar infiltrates) at 72 hours after transplantation. Biomarker profiles were evaluated using logistic regression and generalized estimating equations. Results: Patients who developed PGD had lower protein C levels at 24 hours post-transplantation than patients without PGD (mean 64 ± standard deviation 27% control versus 92 ± 41, p=0.002). Patients with PGD also had PAI-1 levels that were almost double those of patients without PGD at 24 hours (213 ± 144 ng/mL versus 117 +/- 89 ng/mL, respectively, p<0.001). Throughout the 72-hour post-operative period, protein C levels were significantly lower (p=0.007) and PAI-1 levels higher (p=0.026) in PGD subjects than in others. These differences persisted despite adjustment for potential confounders in multivariate analyses. Higher recipient pulmonary artery pressures, measured immediately pretransplant, were associated with higher PAI-1 levels and increased risk of PGD. Conclusion: Lower post-operative protein C and higher PAI-1 plasma levels are associated with PGD following lung transplantation. Impaired fibrinolysis and enhanced coagulation may be important in PGD pathogenesis. Key words: Primary Graft Dysfunction, Reperfusion Injury, Lung Transplantation, Type 1 plasminogen activator inhibitor, Protein C
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
