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(Stroke. 2007;38:90.)
© 2007 American Heart Association, Inc.

Original Contributions

Increased Body Iron Stores Are Associated With Poor Outcome After Thrombolytic Treatment in Acute Stroke

Mónica Millan, MD; Tomás Sobrino, BSc; Mar Castellanos, MD, PhD; Florentino Nombela, MD; Juan F. Arenillas, MD, PhD; Elena Riva, MD; Iván Cristobo, BSc; María M. García, MD, PhD; José Vivancos, MD, PhD; Joaquín Serena, MD, PhD; María A. Moro, PhD; José Castillo, MD Antonio Dávalos, MD, PhD

From the Department of Neurosciences (M.M., J.A., A.D.), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona; Barcelona, Spain; the Department of Neurology (T.S., I.C., J.C.), Hospital Clínico Universitario, Universidad de Santiago de Compostela; the Department of Neurology and Unit of Bioestatistics (M.C., E.R., M.M.G., J.S.), Hospital Doctor Josep Trueta, Girona; the Department of Neurology (F.N., J.V.), Hospital de la Princesa, Madrid, Spain; and the Department of Pharmacology (M.A.M.), School of Medicine, Universidad Complutense, Madrid, Spain.

Correspondence to Mónica Millán, MD, Stroke Unit, Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Barcelona, Spain. E-mail mmillan.germanstrias{at}gencat.net

Background and Purpose— Iron overload has been associated with greater oxidative stress and brain injury in experimental cerebral ischemia and reperfusion. This study investigates whether high serum ferritin levels, as an index of increased cellular iron stores, are associated with poor outcome, hemorrhagic transformation, and brain edema after treatment with tissue plasminogen activator in patients with acute ischemic stroke.

Methods— A total of 134 consecutive patients treated with intravenous tissue plasminogen activator were prospectively studied in four centers. Serum ferritin levels were determined at baseline, 24 and 72 hours after treatment. Cranial computed tomography was performed on admission and at 24 to 36 hours after tissue plasminogen activator infusion. Stroke severity and outcome were evaluated by using the National Institute of Health Stroke Scale and the modified Rankin Scale.

Results— Computed tomography showed hemorrhagic transformation in 27 patients (hemorrhagic infarction in 15 and parenchymal hematoma in 12; symptomatic in four) and brain swelling with midline shift in 15. Poor outcome (modified Rankin Scale >2) at 90 days was observed in 54.5% of patients. Ferritin levels at baseline were higher in patients with poor outcome at 90 days (median [quartiles], 165 [98,307] versus 17 [12,37] ng/mL; P<0.001) and in those who developed parenchymal hematoma (P=0.006), symptomatic hemorrhagic transformation (P=0.008), and severe brain edema (P<0.001). Serum ferritin levels higher than 79 ng/mL before tissue plasminogen activator treatment were independently associated with poor outcome (OR, 117 [95% CI, 25 to 557]).

Conclusions— Increased body iron stores are associated with poor outcome, symptomatic hemorrhagic transformation, and severe edema in patients treated with tissue plasminogen activator after ischemic stroke. These findings suggest that iron overload may offset the beneficial effect of thrombolytic therapies.

Key Words: ferritin • iron overload • ischemic stroke • outcome • oxidative stress • thrombolysis

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