Endogenous activated protein C predicts hemorrhagic transformation and mortality after tissue plasminogen activator treatment in stroke patients

Maite Mendioroz, Israel Fernández-Cadenas, José Alvarez-Sabín, Anna Rosell, Dorita Quiroga, Eloy Cuadrado, Pilar Delgado, Marta Rubiera, Marc Ribó, Carlos Molina, Joan Montaner

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19 Citations (Scopus)

Abstract

Background: Activated protein C (APC) is a plasma serine protease with systemic anticoagulant and a wide spectrum of cytoprotective activities that has been proposed as a promising therapy for acute stroke. Therefore, we sought to investigate the role of endogenous APC in human ischemic stroke. Methods: Our target were 119 consecutive patients with an ischemic stroke involving the middle cerebral artery territory who received tissue plasminogen activator (t-PA) within 3 h of symptom onset. APC was measured before, as well as 1 and 2 h after t-PA administration, and again at 12 and 24 h after stroke onset. Cranial tomography scan was obtained at admission and repeated at 24-48 h or when a neurological worsening occurred to rule out the presence of hemorrhagic complications. The functional outcome was evaluated by 3-month modified Rankin Scale. Results: A total of 117 t-PA-treated patients were finally included in the analyses. APC peaked at 1 h after t-PA administration (pretreatment APC = 132.44 ± 36.39%, 1-hour APC = 184.20 ± 34.28%, 2-hour APC = 145.50 ± 35.23%; p < 0.0001). Interestingly, a high 2-hour APC level was associated with parenchymal hemorrhages (OR = 25.19; 95% CI = 4.76-133.19; p = 0.0001) and mortality (OR = 13.8; 95% CI = 2.58-73.63; p = 0.001), in a logistic regression model. Our results remained significant after Bonferroni correction for multiple testing. Conclusions: A high endogenous APC level 2 h after t-PA administration is independently associated with hemorrhagic transformation and mortality in our cohort of stroke patients. Establishing any causal link for these relationships needs further research. Copyright © 2009 S. Karger AG.
Original languageEnglish
Pages (from-to)143-150
JournalCerebrovascular Diseases
Volume28
Issue number2
DOIs
Publication statusPublished - 1 Jul 2009

Keywords

  • Activated protein C
  • Coagulation
  • Plasmin
  • Stroke
  • Thrombolysis

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