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  • Title: Endogenous activated protein C predicts hemorrhagic transformation and mortality after tissue plasminogen activator treatment in stroke patients.
    Author: Mendioroz M, Fernández-Cadenas I, Alvarez-Sabín J, Rosell A, Quiroga D, Cuadrado E, Delgado P, Rubiera M, Ribó M, Molina C, Montaner J.
    Journal: Cerebrovasc Dis; 2009; 28(2):143-50. PubMed ID: 19546541.
    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.
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