Plasma cellular-fibronectin concentration predicts hemorrhagic transformation after thrombolytic therapy in acute ischemic stroke.
OBJECTIVE
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 microg/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.
Castellanos
Mar
M
Department of Neurology, Hospital Universitari Doctor Josep Trueta in affiliation with the UAB, Avda Francia s/n, Girona-17007, Spain. nrl.mcastellanos@htrueta.scs.es
Leira
Rogelio
R
Serena
Joaquín
J
Blanco
Miguel
M
Pedraza
Salvador
S
Castillo
José
J
Dávalos
Antoni
A
D000368:Aged; D002545:Brain Ischemia / Q000097:blood; D005260:Female; D005353:Fibronectins / Q000097:blood*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012306:Risk; D020521:Stroke / Q000097:blood* / Q000145:classification / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed
D005353:Fibronectins; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9