Increased body iron stores are associated with poor outcome after thrombolytic treatment in acute stroke.
OBJECTIVE
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.
Millan
Mónica
M
Stroke Unit, Department of Neurosciences, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Barcelona, Spain. mmillan.germanstrias@gencat.net
Sobrino
Tomás
T
Castellanos
Mar
M
Nombela
Florentino
F
Arenillas
Juan F
JF
Riva
Elena
E
Cristobo
Iván
I
García
María M
MM
Vivancos
José
J
Serena
Joaquín
J
Moro
María A
MA
Castillo
José
J
Dávalos
Antonio
A
D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D015984:Causality; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D005293:Ferritins / Q000097:blood; D005343:Fibrinolytic Agents / Q000009:adverse effects; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D020521:Stroke / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D005293:Ferritins; D007501:Iron; D010959:Tissue Plasminogen Activator