Admission Fibrinolytic Profile Is Associated With Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Tissue Plasminogen Activator

Background and Purpose— Symptomatic intracranial hemorrhage (SICH) is the most feared complication after tissue plasminogen activator (tPA) stroke treatment. Endogenous fibrinolysis inhibitors play an essential role in the coagulation/fibrinolysis balance and may be involved in the bleeding process. We aim to determine the predictive value of pretreatment levels of fibrinolysis inhibitors (PAI-1, lipoprotein(a), TAFI, and homocysteine) on SICH. Methods— Consecutive tPA-treated stroke patients with middle cerebral artery occlusion were studied. Baseline blood samples were obtained just before tPA administration and fibrinolysis inhibitors were determined. A second computed tomography (CT) scan was obtained at 24 hours or when a neurological worsening occurred to rule out SICH. Results— Seventy-seven patients (40% women, age 75 years) were studied. Median admission National Institutes of Health Stroke Scale was 17 (range, 7 to 22) and mean time to treatment was 160 minutes. Six patients (7.9%) presented with a SICH. In analyses based on clinical and CT variables, no relation could be found with SICH. When laboratory data were analyzed, patients who experienced SICH showed lower baseline PAI-1 (21.7±3.5 ng/mL versus 31.8±12.1 ng/mL; P < 0.01) and higher TAFI (216.7±78.4% versus 162.1±54.2%; P = 0.03). Homocysteine and lipoprotein(a) were not related to SICH. The only factors associated with SICH were TAFI >180% (OR, 12.9; CI, 1.41 to 118.8; P = 0.02) and PAI-1 <21.4 ng/mL (OR, 12.75; CI, 1.17 to 139.2; P = 0.04). The combination of admission PAI-1 <21.4 ng/mL and TAFI >180% had a sensibility of 75% and a specificity of 97.6% (P <0.01) predicting SICH, with a positive predictive value of 75% and negative predictive value of 97.6%. Conclusions— Baseline PAI-1 and TAFI levels predict SICH after stroke tPA therapy. In the future, these biomarkers could be used to improve thrombolysis safety.

[1]  M. Burns,et al.  Case-Control Study , 2020, Definitions.

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

[3]  A. Gils,et al.  The structural basis for the pathophysiological relevance of PAI-1 in cardiovascular diseases and the development of potential PAI-1 inhibitors , 2004, Thrombosis and Haemostasis.

[4]  E. Thompson,et al.  Temporal Alterations in Cerebrospinal Fluid Amyloid &bgr;-Protein and Apolipoprotein E After Subarachnoid Hemorrhage , 2003, Stroke.

[5]  P. Akins,et al.  How Effective Are “Community” Stroke Screening Programs at Improving Stroke Knowledge and Prevention Practices?: Results of a 3-Month Follow-Up Study , 2003, Stroke.

[6]  P. Morange,et al.  Very high TAFI antigen levels are associated with a lower risk of hard coronary events: the PRIME Study , 2003, Journal of thrombosis and haemostasis : JTH.

[7]  E. Vicaut,et al.  Acute Release of Plasminogen Activator Inhibitor-1 in ST-Segment Elevation Myocardial Infarction Predicts Mortality , 2003, Circulation.

[8]  R. Knight,et al.  Hemorrhagic transformation is related to the duration of occlusion and treatment with tissue plasminogen activator in a nonembolic stroke model , 2003, Neurological research.

[9]  P. Heuschmann,et al.  Frequency of Thrombolytic Therapy in Patients With Acute Ischemic Stroke and the Risk of In-Hospital Mortality: The German Stroke Registers Study Group , 2003, Stroke.

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

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

[12]  I. Kovács,et al.  Görög Thrombosis Test: a global in-vitro test of platelet function and thrombolysis , 2003, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[13]  Andrew M. Demchuk,et al.  Markers of Increased Risk of Intracerebral Hemorrhage After Intravenous Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke in Clinical Practice: The Multicenter rt-PA Acute Stroke Survey , 2002, Circulation.

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

[15]  D. Tanné,et al.  Predictors of good outcome after intravenous tPA for acute ischemic stroke , 2001, Neurology.

[16]  E. Angles-cano,et al.  Inhibition of Fibrinolysis by Lipoprotein(a) , 2001, Annals of the New York Academy of Sciences.

[17]  K. Kolev,et al.  Perturbation of the integrity of the blood‐brain barrier by fibrinolytic enzymes , 1998, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[18]  A. Alexandrov,et al.  Predictors of hemorrhagic transformation occurring spontaneously and on anticoagulants in patients with acute ischemic stroke. , 1997, Stroke.

[19]  V Larrue,et al.  Hemorrhagic transformation in acute ischemic stroke. Potential contributing factors in the European Cooperative Acute Stroke Study. , 1997, Stroke.

[20]  T. N. t-P. S. S. Group,et al.  Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group. , 1997, Stroke.

[21]  P D Lyden,et al.  Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a Special Writing Group of the Stroke Council, American Heart Association. , 1996, Circulation.

[22]  J. Grotta,et al.  Guidelines for Thrombolytic Therapy for Acute Stroke: a Supplement to the Guidelines for the Management of Patients with Acute Ischemic Stroke. A statement for healthcare professionals from a Special Writing Group of the Stroke Council, American Heart Association. , 1996, Stroke.

[23]  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 .

[24]  M. Kaste,et al.  Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS) , 1995, JAMA.

[25]  M. Nesheim,et al.  Purification and Characterization of TAFI, a Thrombin-activable Fibrinolysis Inhibitor (*) , 1995, The Journal of Biological Chemistry.

[26]  K. Hajjar.  Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor. , 1993, The Journal of clinical investigation.

[27]  David Lee Gordon,et al.  Classification of Subtype of Acute Ischemic Stroke: Definitions for Use in a Multicenter Clinical Trial , 1993, Stroke.

[28]  M. Kaste,et al.  The European Cooperative Acute Stroke Study (ECASS) , 1993 .

[29]  J. Broderick,et al.  Urgent Therapy for Stroke: Part I. Pilot Study of Tissue Plasminogen Activator Administered Within 90 Minutes , 1992, Stroke.