Update on the Serum Biomarkers and Genetic Factors Associated with Safety and Efficacy of rt-PA Treatment in Acute Stroke Patients

An accurate understanding of the mechanisms underlying an individual's response to rt-PA treatment is critical to improve stroke patients' management. We thus reviewed the literature in order to identify biochemical and genetic factors that have been associated with safety and efficacy of rt-PA administration after stroke.

[1]  D. Fatovich,et al.  Thrombolysis in acute ischaemic stroke , 2012, The Lancet.

[2]  J. Montaner,et al.  The Proteome of Human Brain After Ischemic Stroke , 2010, Journal of neuropathology and experimental neurology.

[3]  J. Álvarez-Sabín,et al.  The I/D polymorphism of the ACE1 gene is not associated with ischaemic stroke in Spanish individuals , 2010, European journal of neurology.

[4]  C. Molina,et al.  Plasma VAP-1/SSAO Activity Predicts Intracranial Hemorrhages and Adverse Neurological Outcome After Tissue Plasminogen Activator Treatment in Stroke , 2010, Stroke.

[5]  Gregory W Albers,et al.  Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials , 2010, The Lancet.

[6]  A. Daly,et al.  Genome-wide association studies in pharmacogenomics , 2010, Nature Reviews Genetics.

[7]  C. Molina,et al.  Oxidative Stress After Thrombolysis-Induced Reperfusion in Human Stroke , 2010, Stroke.

[8]  T. J. Schaewe,et al.  Blood–Brain Barrier Disruption in Humans Is Independently Associated With Increased Matrix Metalloproteinase-9 , 2010, Stroke.

[9]  L. Goldstein,et al.  Hospital Arrival Time and Intravenous t-PA Use in US Academic Medical Centers, 2001–2004 , 2009, Stroke.

[10]  À. Rovira,et al.  Lower concentrations of thrombin-antithrombin complex (TAT) correlate to higher recanalisation rates among ischaemic stroke patients treated with t-PA , 2009, Thrombosis and Haemostasis.

[11]  M. Lansberg,et al.  Efficacy and Safety of Tissue Plasminogen Activator 3 to 4.5 Hours After Acute Ischemic Stroke: A Metaanalysis , 2009, Stroke.

[12]  C. Molina,et al.  Endogenous Activated Protein C Predicts Hemorrhagic Transformation and Mortality after Tissue Plasminogen Activator Treatment in Stroke Patients , 2009, Cerebrovascular Diseases.

[13]  Gary A. Ford,et al.  Multivariable Analysis of Outcome Predictors and Adjustment of Main Outcome Results to Baseline Data Profile in Randomized Controlled Trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) , 2008, Stroke.

[14]  J. Montaner,et al.  Tissue plasminogen activator (t‐PA) promotes neutrophil degranulation and MMP‐9 release , 2008, Journal of leukocyte biology.

[15]  E. Lo,et al.  MMP-9–Positive Neutrophil Infiltration Is Associated to Blood–Brain Barrier Breakdown and Basal Lamina Type IV Collagen Degradation During Hemorrhagic Transformation After Human Ischemic Stroke , 2008, Stroke.

[16]  J. Martí-Fàbregas,et al.  Change in Hemostatic Markers After Recombinant Tissue-Type Plasminogen Activator Is Not Associated With the Chance of Recanalization , 2008, Stroke.

[17]  J. Montaner,et al.  Influence of thrombin‐activatable fibrinolysis inhibitor and plasminogen activator inhibitor‐1 gene polymorphisms on tissue‐type plasminogen activator‐induced recanalization in ischemic stroke patients , 2007, Journal of thrombosis and haemostasis : JTH.

[18]  J. Arenillas,et al.  Serum Cellular Fibronectin and Matrix Metalloproteinase-9 as Screening Biomarkers for the Prediction of Parenchymal Hematoma After Thrombolytic Therapy in Acute Ischemic Stroke: A Multicenter Confirmatory Study , 2007, Stroke.

[19]  Werner Hacke,et al.  Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study , 2007, The Lancet.

[20]  José A Fernández,et al.  Activated protein C inhibits tissue plasminogen activator–induced brain hemorrhage , 2006, Nature Medicine.

[21]  J. Serena,et al.  Micro- and macroalbuminuria predict hemorrhagic transformation in acute ischemic stroke , 2006, Neurology.

[22]  J. Montaner,et al.  Role of Fibrinogen Levels and Factor XIII V34L Polymorphism in Thrombolytic Therapy in Stroke Patients , 2006, Stroke.

[23]  D. Tanné,et al.  Hemostatic Activation and Outcome After Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke , 2006, Stroke.

[24]  C. Molina,et al.  ACE gene polymorphisms influence t-PA-induced brain vessel reopening following ischemic stroke , 2006, Neuroscience Letters.

[25]  José A Fernández,et al.  The promise of protein C. , 2006, Blood cells, molecules & diseases.

[26]  A. Oncul,et al.  The association between factor XIII Val34Leu polymorphism and early myocardial infarction. , 2006, Circulation journal : official journal of the Japanese Circulation Society.

[27]  J. Montaner,et al.  Hemostatic markers of recanalization in patients with ischemic stroke treated with rt-PA , 2005, Neurology.

[28]  A. Hamsten,et al.  Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke: Replicated Findings in Two Nested Case–Control Studies Based on Independent Cohorts , 2005, Stroke.

[29]  A. Słowik,et al.  Coagulation Factor XIII VaI34Leu Polymorphism in Patients with Small Vessel Disease or Primary Intracerebral Hemorrhage , 2005, Cerebrovascular Diseases.

[30]  J. Arenillas,et al.  Admission Fibrinolytic Profile Is Associated With Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Tissue Plasminogen Activator , 2004, Stroke.

[31]  Bronwyn A. Kingwell,et al.  Matrix Metalloproteinase-9 Genotype Influences Large Artery Stiffness Through Effects on Aortic Gene and Protein Expression , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[32]  S. Pedraza,et al.  Plasma Cellular-Fibronectin Concentration Predicts Hemorrhagic Transformation After Thrombolytic Therapy in Acute Ischemic Stroke , 2004, Stroke.

[33]  Scott Hamilton,et al.  Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials , 2004, The Lancet.

[34]  I. Tkáč,et al.  Angiotensin-converting enzyme genotype, albuminuria and plasma fibrinogen in type 2 diabetes mellitus , 2003, Wiener Klinische Wochenschrift.

[35]  A. Alexandrov,et al.  Improving the Predictive Accuracy of Recanalization on Stroke Outcome in Patients Treated With Tissue Plasminogen Activator , 2003, Stroke.

[36]  J. Geleijnse,et al.  4G/4G Genotype of PAI-1 Gene Is Associated With Reduced Risk of Stroke in Elderly , 2003, Stroke.

[37]  Gregory T. Jones,et al.  Functional matrix metalloproteinase-9 polymorphism (C-1562T) associated with abdominal aortic aneurysm. , 2003, Journal of vascular surgery.

[38]  G. D. Graham,et al.  Tissue Plasminogen Activator for Acute Ischemic Stroke in Clinical Practice: A Meta-Analysis of Safety Data , 2003, Stroke.

[39]  J. Arenillas,et al.  Safety Profile of Tissue Plasminogen Activator Treatment Among Stroke Patients Carrying a Common Polymorphism (C-1562T) in the Promoter Region of the Matrix Metalloproteinase-9 Gene , 2003, Stroke.

[40]  J. Martí-Fàbregas,et al.  Risk of Ischemic Stroke Associated With Functional Thrombin-Activatable Fibrinolysis Inhibitor Plasma Levels , 2003, Stroke.

[41]  J. M. Wardlaw,et al.  Thrombolytic Therapy With Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke: Where Do We Go From Here? A Cumulative Meta-Analysis , 2003, Stroke.

[42]  K. Saku,et al.  Angiotensin‐converting enzyme insertion/deletion genotype is associated with the activities of plasma coagulation factor VII and X independent of triglyceride metabolism , 2003, Coronary artery disease.

[43]  R. Donato,et al.  Intracellular and extracellular roles of S100 proteins , 2003, Microscopy research and technique.

[44]  F. Cambien,et al.  Plasma Concentrations and Genetic Variation of Matrix Metalloproteinase 9 and Prognosis of Patients With Cardiovascular Disease , 2003, Circulation.

[45]  C. Molina,et al.  Thrombin-Activable Fibrinolysis Inhibitor Levels in the Acute Phase of Ischemic Stroke , 2003, Stroke.

[46]  José A Fernández,et al.  Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective , 2003, Nature Medicine.

[47]  J. Arenillas,et al.  Matrix Metalloproteinase-9 Pretreatment Level Predicts Intracranial Hemorrhagic Complications After Thrombolysis in Human Stroke , 2003, Circulation.

[48]  J. Serena,et al.  Plasma Metalloproteinase-9 Concentration Predicts Hemorrhagic Transformation in Acute Ischemic Stroke , 2003, Stroke.

[49]  G. Rosenberg.  Matrix metalloproteinases in neuroinflammation , 2002, Glia.

[50]  E. Lo,et al.  Extracellular proteolysis in brain injury and inflammation: Role for plasminogen activators and matrix metalloproteinases , 2002, Journal of neuroscience research.

[51]  Bruce M Psaty,et al.  The Association of PAI-1 Promoter 4G/5G Insertion/Deletion Polymorphism with Myocardial Infarction and Stroke in Young Women , 2002, Journal of cardiovascular risk.

[52]  M. Boffa,et al.  Two Naturally Occurring Variants of TAFI (Thr-325 and Ile-325) Differ Substantially with Respect to Thermal Stability and Antifibrinolytic Activity of the Enzyme* , 2002, The Journal of Biological Chemistry.

[53]  J. Arenillas,et al.  Time Course of Tissue Plasminogen Activator–Induced Recanalization in Acute Cardioembolic Stroke: A Case-Control Study , 2001, Stroke.

[54]  A. Reiner,et al.  Polymorphisms of Coagulation Factor XIII Subunit A and Risk of Nonfatal Hemorrhagic Stroke in Young White Women , 2001, Stroke.

[55]  L. Gelbert,et al.  Gene Expression Profile of Antithrombotic Protein C Defines New Mechanisms Modulating Inflammation and Apoptosis* , 2001, The Journal of Biological Chemistry.

[56]  J Ean,et al.  Efficacy and safety of recombinant human activated protein C for severe sepsis. , 2001, The New England journal of medicine.

[57]  D. DeMets,et al.  Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework , 2001, Clinical pharmacology and therapeutics.

[58]  A. Alexandrov,et al.  Thrombolysis in Brain Ischemia (TIBI) Transcranial Doppler Flow Grades Predict Clinical Severity, Early Recovery, and Mortality in Patients Treated With Intravenous Tissue Plasminogen Activator , 2001, Stroke.

[59]  J. Weisel,et al.  The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII and affects cross-linked fibrin structure. , 2000, Blood.

[60]  A. Alexandrov,et al.  Timing of recanalization after tissue plasminogen activator therapy determined by transcranial doppler correlates with clinical recovery from ischemic stroke. , 2000, Stroke.

[61]  P. Verhallen,et al.  An inhibitor of activated thrombin-activatable fibrinolysis inhibitor potentiates tissue-type plasminogen activator-induced thrombolysis in a rabbit jugular vein thrombolysis model. , 2000, Thrombosis research.

[62]  D. Blacker,et al.  High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial Doppler monitoring. , 2000, Stroke.

[63]  L. Tiret,et al.  Genetic Polymorphisms and Coronary Artery Disease in the South of France , 2000, Thrombosis and Haemostasis.

[64]  M. Fujimura,et al.  Early appearance of activated matrix metalloproteinase-9 and blood–brain barrier disruption in mice after focal cerebral ischemia and reperfusion , 1999, Brain Research.

[65]  K. Lees,et al.  C-reactive protein and outcome after ischemic stroke. , 1999, Stroke.

[66]  A. Evans,et al.  Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. , 1999, Circulation.

[67]  A. J. Man in 't Veld,et al.  Circulating semicarbazide-sensitive amine oxidase is raised both in Type I (insulin-dependent), in Type II (non-insulin-dependent) diabetes mellitus and even in childhood Type I diabetes at first clinical diagnosis , 1999, Diabetologia.

[68]  P. A. von dem Borne,et al.  Plasma TAFI Levels Influence the Clot Lysis Time in Healthy Individuals in the Presence of an Intact Intrinsic Pathway of Coagulation , 1998, Thrombosis and Haemostasis.

[69]  J. Enghild,et al.  Human Procarboxypeptidase U, or Thrombin-activable Fibrinolysis Inhibitor, Is a Substrate for Transglutaminases , 1998, The Journal of Biological Chemistry.

[70]  F. Barone,et al.  Matrix metalloproteinase expression increases after cerebral focal ischemia in rats: inhibition of matrix metalloproteinase-9 reduces infarct size. , 1998, Stroke.

[71]  A. Carter,et al.  Factor XIII Val 34 Leu: a novel association with primary intracerebral hemorrhage. , 1998, Stroke.

[72]  W. R. Lee,et al.  Polymorphism of angiotensin converting enzyme gene is associated with circulating levels of plasminogen activator inhibitor-1. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[73]  M. Margaglione,et al.  Plasminogen activator inhibitor-1 (PAI-1) antigen plasma levels in subjects attending a metabolic ward: relation to polymorphisms of PAI-1 and angiontensin converting enzyme (ACE) genes. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[74]  A. Carter,et al.  Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G Promoter Polymorphism and Levels in Subjects with Cerebrovascular Disease , 1997, Thrombosis and Haemostasis.

[75]  A. Mosterd,et al.  Plasma semicarbazide-sensitive amine oxidase is elevated in patients with congestive heart failure. , 1997, Cardiovascular research.

[76]  B. Norrving,et al.  Tissue plasminogen activator and plasminogen activator inhibitor-1 in stroke patients. , 1996, Stroke.

[77]  Koroshetz Wj,et al.  Tissue plasminogen activator for acute ischemic stroke. , 1996, The New England journal of medicine.

[78]  Gary A. Rosenberg,et al.  Proteolytic Cascade Enzymes Increase in Focal Cerebral Ischemia in Rat , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[79]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

[80]  S. Humphries,et al.  The 4G/5G Genetic Polymorphism in the Promoter of the Plasminogen Activator Inhibitor-1 (PAI-1) Gene Is Associated with Differences in Plasma PAI-1 Activity but not with Risk of Myocardial Infarction in the ECTIM Study , 1995, Thrombosis and Haemostasis.

[81]  M. Margaglione,et al.  Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with a history of ischemic stroke. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[82]  D. Loskutoff,et al.  Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[83]  P Corvol,et al.  An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. , 1990, The Journal of clinical investigation.

[84]  A. Woolf,et al.  Elevated plasma levels of ED1+ ("cellular") fibronectin in patients with vascular injury. , 1989, The Journal of laboratory and clinical medicine.

[85]  M. Blombäck,et al.  PLASMINOGEN ACTIVATOR INHIBITOR IN PLASMA: RISK FACTOR FOR RECURRENT MYOCARDIAL INFARCTION , 1987, The Lancet.

[86]  JH Darrell,et al.  Medical Microbiology , 1983 .

[87]  H. Steinmetz,et al.  Elevated serum S100B levels indicate a higher risk of hemorrhagic transformation after thrombolytic therapy in acute stroke. , 2007, Stroke.

[88]  J. Griffin,et al.  bloodjournal.hematologylibrary.org at PENN STATE UNIVERSITY on February 21, 2013. For personal use only. The cytoprotective protein C pathway , 2006 .

[89]  M. Moskowitz,et al.  Neurological diseases: Mechanisms, challenges and opportunities in stroke , 2003, Nature Reviews Neuroscience.

[90]  A. Alexandrov,et al.  High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial doppler monitoring. , 2000, Stroke.

[91]  J. Corral,et al.  The FXIII Val34Leu polymorphism in venous and arterial thromboembolism. , 2000, Haematologica.

[92]  P. Grant,et al.  Association of a common polymorphism in the factor XIII gene with venous thrombosis. , 1999, Blood.

[93]  J. Álvarez-Sabín,et al.  Admission fibrinolytic profile predicts clot lysis resistance in stroke patients treated with tissue plasminogen activator , 2004, Thrombosis and Haemostasis.

[94]  V. Kunzmann,et al.  A novel , possibly functional , single nucleotide polymorphism in the coding region of the thrombin-activatable fibrinolysis inhibitor ( TAFI ) gene is also associated with TAFI levels , 2022 .