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

Jason D. Christie, Nancy Robinson, Lorraine B. Ware, Michael Plotnick, Joao De Andrade, Vibha Lama, Aaron Milstone, Jonathan Orens, Ann Weinacker, Ejigayehu Demissie, Scarlett Bellamy, Steven M. Kawut

Research output: Contribution to journalArticlepeer-review

Abstract

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 6, 24, 48, and 72 h after allograft reperfusion in 128 lung transplant recipients at six centers. The primary outcome was grade 3 PGD (PaO2/FIO2 < 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)69-74
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume175
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • Lung transplantation
  • Primary graft dysfunction
  • Protein C
  • Reperfusion injury
  • Type 1 plasminogen activator inhibitor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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