title: Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes.
abstract: OBJECTIVE
  To determine whether higher neutrophil counts before IV recombinant tissue plasminogen activator (rtPA) administration in ischemic stroke (IS) patients are associated with symptomatic intracerebral hemorrhages (sICH) and worse outcomes at 3 months.
  
  
  METHODS
  Blood samples for leukocyte, neutrophil, and lymphocyte counts were drawn before IV rtPA administration in IS patients included in the cohorts of Lille and Helsinki. The primary endpoint was sICH (European Cooperative Acute Stroke-II definition). Secondary endpoints were death and excellent (modified Rankin Scale [mRS] score 0-1 or equal to prestroke mRS) and good (mRS score 0-2 or equal to prestroke mRS) outcomes at 3 months.
  
  
  RESULTS
  We included 846 patients (median age 71 years; 50.8% men). The neutrophil count and neutrophil to lymphocyte ratio (NLR) were independently associated with the 4 endpoints: sICH (adjusted odds ratio [adjOR] for an increase of 1,000 neutrophils = 1.21 and adjOR 1.11, respectively), death (adjOR 1.16 and adjOR 1.08), and excellent (adjOR 0.87 and adjOR 0.85) and good (adjOR 0.86 and adjOR 0.91) outcomes. The total leukocyte count was not associated with any of the 4 endpoints. The best discriminating factor for sICH was NLR ≥4.80 (sensitivity 66.7%, specificity 71.3%, likelihood ratio 2.32). Patients with NLR ≥4.80 had a 3.71-fold increased risk for sICH (95% confidence interval adjOR: 1.97-6.98) compared to patients with NLR <4.80.
  
  
  CONCLUSIONS
  Higher neutrophil counts and NLR are independently associated with sICH and worse outcome at 3 months. The identification of mediators of this effect could provide new targets for neuroprotection in patients treated by rtPA.
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Maestrini
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Strbian
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gautier
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Elena
authors.initials: E
authors.lastname: Haapaniemi
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Solène
authors.initials: S
authors.lastname: Moulin
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Sairanen
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Nelly
authors.initials: N
authors.lastname: Dequatre-Ponchelle
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Gerli
authors.initials: G
authors.lastname: Sibolt
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cordonnier
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Melkas
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland. didier.leys@univ-lille2.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Leys
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Turgut
authors.initials: T
authors.lastname: Tatlisumak
authors.affiliation: From the Departments of Neurology (I.M., S.G., S. Moulin, N.D.-P., C.C., D.L., R.B.) and Pharmacology (S. Moulin, N.D.-P., C.C., D.L.), INSERM U 1171, University of Lille, UDSL; CHU Lille (S.G., R.B.), France; "Sapienza" University of Rome (I.M.), Italy; and the Department of Neurology (D.S., E.H., T.S., G.S., S. Melkas, T.T.), Helsinki University Central Hospital, Finland.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000139:chemically induced* / Q000175:diagnosis; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D010959:Tissue Plasminogen Activator