Association of protein C and type 1 plasminogen activator inhibitor with primary graft dysfunction.
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.


METHODS
Prospective, multicenter cohort study.


METHODS
We measured plasma levels of protein C and PAI-1 before lung transplantation and 6, 24, 48, and 72 h after allograft reperfusion in 128 lung transplant recipients at six centers. The primary outcome was grade 3 PGD (Pa(O(2))/Fi(O(2)) < 200 with alveolar infiltrates) 72 h after transplantation. Biomarker profiles were evaluated using logistic regression and generalized estimating equations.


RESULTS
Patients who developed PGD had lower protein C levels 24 h posttransplantation than did patients without PGD (mean +/- SD [relative to control]: 64 +/- 27 vs. 92 +/- 41%, respectively; p = 0.002). Patients with PGD also had PAI-1 levels that were almost double those of patients without PGD at 24 h (213 +/- 144 vs. 117 +/- 89 ng/ml, respectively; p < 0.001). Throughout the 72-h postoperative period, protein C levels were significantly lower (p = 0.007) and PAI-1 levels were higher (p = 0.026) in subjects with PGD than in others. These differences persisted despite adjustment for potential confounders in multivariate analyses. Higher recipient pulmonary artery pressures, measured immediately pretransplantation, were associated with higher PAI-1 levels and increased risk of PGD.


CONCLUSIONS
Lower postoperative protein C and higher PAI-1 plasma levels are associated with PGD after lung transplantation. Impaired fibrinolysis and enhanced coagulation may be important in PGD pathogenesis.
Christie
Jason D
JD
Division of Pulmonary, Allergy, and Critical Care Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. jchristi@cceb.med.upenn.edu
Robinson
Nancy
N
Ware
Lorraine B
LB
Plotnick
Michael
M
De Andrade
Joao
J
Lama
Vibha
V
Milstone
Aaron
A
Orens
Jonathan
J
Weinacker
Ann
A
Demissie
Ejigayehu
E
Bellamy
Scarlett
S
Kawut
Steven M
SM
D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D005260:Female; D005342:Fibrinolysis; D006084:Graft Rejection / Q000209:etiology*; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011486:Protein C / Q000032:analysis*
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C