title: Endogenous activated protein C predicts hemorrhagic transformation and mortality after tissue plasminogen activator treatment in stroke patients.
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.
authors: Neurovascular Research Laboratory, Neurovascular Unit, Neurology Department, Internal Medicine Department, Vall d'Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Maite
authors: M
authors: Mendioroz
authors: Israel
authors: I
authors: Fernández-Cadenas
authors: José
authors: J
authors: Alvarez-Sabín
authors: Anna
authors: A
authors: Rosell
authors: Dorita
authors: D
authors: Quiroga
authors: Eloy
authors: E
authors: Cuadrado
authors: Pilar
authors: P
authors: Delgado
authors: Marta
authors: M
authors: Rubiera
authors: Marc
authors: M
authors: Ribó
authors: Carlos
authors: C
authors: Molina
authors: Joan
authors: J
authors: Montaner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D007262:Infusions, Intravenous; D020300:Intracranial Hemorrhages / Q000097:blood / Q000209:etiology* / Q000401:mortality*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011486:Protein C / Q000378:metabolism*; D012372:ROC Curve; D018570:Risk Assessment; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D005343:Fibrinolytic Agents; D011486:Protein C; D010959:Tissue Plasminogen Activator