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(Stroke. 2004;35:1671.)
© 2004 American Heart Association, Inc.

Original Contributions

Plasma Cellular-Fibronectin Concentration Predicts Hemorrhagic Transformation After Thrombolytic Therapy in Acute Ischemic Stroke

Mar Castellanos, MD; Rogelio Leira, MD, PhD; Joaquín Serena, MD, PhD; Miguel Blanco, MD, PhD; Salvador Pedraza, MD; José Castillo, MD, PhD Antoni Dávalos, MD, PhD

From the Departments of Neurology (M.C., J.S., A.D.) and Neuroradiology (S.P.), Hospital Universitari Doctor Josep Trueta, Girona, Spain; and the Department of Neurology, Hospital Clínico Universitario de Santiago (R.L., M.B., J.C.), Santiago de Compostela, Spain.

Correspondence to Dr Mar Castellanos, Department of Neurology, Hospital Universitari Doctor Josep Trueta in affiliation with the UAB, Avda Francia s/n, Girona-17007, Spain. E-mail nrl.mcastellanos{at}htrueta.scs.es

Background and Purpose— Elevated plasma levels of cellular fibronectin (c-Fn) reflect vascular damage, so c-Fn might be a marker of secondary bleeding risk in cerebral ischemia. We investigated whether high plasma levels of c-Fn were associated with hemorrhagic transformation (HT) after treatment with tissue plasminogen activator (tPA) in patients with acute stroke.

Methods— Eighty-seven patients (mean age: 67±12) received tPA after the ECASS II criteria (mean time to infusion: 160±46 minutes; median NIHSS: 12). HT and hypodensity volume were studied on computed tomography (CT) performed 24 to 36 hours after treatment. HT was classified according to the ECASS II definitions. c-Fn and matrix metalloproteinase 9 (MMP-9) levels were determined by ELISA in blood samples obtained before treatment and in 30 healthy subjects.

Results— HT was found in 26 patients (30%); 15 patients had hemorrhagic infarction type 1 (HI-1), 7 had HI-2, and 4 had parenchymal hemorrhage (PH). Median c-Fn concentrations were 1.3, 1.7, 4.2, 5.4, and 7.3 µg/mL in controls, non-HT, HI-1, HI-2, and PH groups, respectively (P<0.001); median MMP-9 values were 54, 87, 154, 176, and 225 ng/mL (P<0.001). Logistic regression analysis showed that only c-Fn plasma levels remained independently associated with HT after adjusting for potential confounders (OR, 2.1; 95% CI, 1.3 to 3.4; P=0.002). Similar results were obtained in the 71 patients treated within 3 hours.

Conclusions— High plasma c-Fn levels are significantly associated with subsequent HT in stroke patients treated with tPA, so plasma c-Fn determinations might be useful in clinical practice to improve the risk/benefit ratio of thrombolytic treatment.

Key Words: stroke • stroke, acute • hemorrhage • thrombolytic therapy

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