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 B Orens, Ann Weinacker, Ejigayehu Demissie, Scarlett Bellamy, Steven M. Kawut

Research output: Contribution to journalArticle

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
Externally publishedYes

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Primary Graft Dysfunction
Plasminogen Activator Inhibitor 1
Protein C
Lung Transplantation
Fibrinolysis
Thrombophilia
Acute Lung Injury
Postoperative Period
Pulmonary Artery
Multicenter Studies
Reperfusion
Allografts
Blood Proteins

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Association of protein C and type 1 plasminogen activator inhibitor with primary graft dysfunction. / Christie, Jason D.; Robinson, Nancy; Ware, Lorraine B.; Plotnick, Michael; De Andrade, Joao; Lama, Vibha; Milstone, Aaron; Orens, Jonathan B; Weinacker, Ann; Demissie, Ejigayehu; Bellamy, Scarlett; Kawut, Steven M.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 175, No. 1, 01.01.2007, p. 69-74.

Research output: Contribution to journalArticle

Christie, JD, Robinson, N, Ware, LB, Plotnick, M, De Andrade, J, Lama, V, Milstone, A, Orens, JB, Weinacker, A, Demissie, E, Bellamy, S & Kawut, SM 2007, 'Association of protein C and type 1 plasminogen activator inhibitor with primary graft dysfunction', American Journal of Respiratory and Critical Care Medicine, vol. 175, no. 1, pp. 69-74. https://doi.org/10.1164/rccm.200606-827OC
Christie, Jason D. ; Robinson, Nancy ; Ware, Lorraine B. ; Plotnick, Michael ; De Andrade, Joao ; Lama, Vibha ; Milstone, Aaron ; Orens, Jonathan B ; Weinacker, Ann ; Demissie, Ejigayehu ; Bellamy, Scarlett ; Kawut, Steven M. / Association of protein C and type 1 plasminogen activator inhibitor with primary graft dysfunction. In: American Journal of Respiratory and Critical Care Medicine. 2007 ; Vol. 175, No. 1. pp. 69-74.
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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.",
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T1 - Association of protein C and type 1 plasminogen activator inhibitor with primary graft dysfunction

AU - Christie, Jason D.

AU - Robinson, Nancy

AU - Ware, Lorraine B.

AU - Plotnick, Michael

AU - De Andrade, Joao

AU - Lama, Vibha

AU - Milstone, Aaron

AU - Orens, Jonathan B

AU - Weinacker, Ann

AU - Demissie, Ejigayehu

AU - Bellamy, Scarlett

AU - Kawut, Steven M.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - 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.

AB - 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.

KW - Lung transplantation

KW - Primary graft dysfunction

KW - Protein C

KW - Reperfusion injury

KW - Type 1 plasminogen activator inhibitor

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