Published Online
on March 19, 2009

A more recent version of this article appeared on May 1, 2009

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Submitted on June 5, 2008
Revised on August 20, 2008
Accepted on August 29, 2008

Hyperfibrinogenemia and Functional Outcome From Acute Ischemic Stroke

Gregory J. del Zoppo MD, PhD^*; David E. Levy MD; Warren W. Wasiewski MD; Arthur M. Pancioli MD; Andrew M. Demchuk MD; James Trammel MS; Bart M. Demaerschalk MD; Markku Kaste MD, PhD; Gregory W. Albers MD; and Eric B. Ringelstein MD

From Harborview Medical Center (G.J.d.Z.), University of Washington, Seattle, Wash, USA; i3Statprobe (J.T.), Stonewall, La, USA; Neurobiological Technologies, Inc (D.E.L., W.W.W.), Edgewater, NJ, USA; Mayo Clinic Hospital (B.M.D.), Phoenix, Ariz, USA; Helsinki University General Hospital (M.K.), University of Helsinki, Helsinki, Finland; University Hospital (A.M.P.), Cincinnati, Ohio, USA; Stanford University Medical Center (G.W.A.), Palo Alto, Calif, USA; University of Calgary Foothills Medical Centre (A.M.D.), Calgary, Alberta, Canada; University Hospital Münster (E.B.R.), Münster, Germany.

^* To whom correspondence should be addressed. E-mail: grgdlzop{at}u.washington.edu.

Background and Purpose—Epidemiological studies have found strong correlations between elevated plasma fibrinogen levels and both ischemic stroke incidence and stroke mortality. Little is known about the influence of fibrinogen levels on functional stroke outcome.

Methods—Placebo data from the Stroke Treatment with Ancrod Trial (STAT) and European Stroke Treatment with Ancrod Trial (ESTAT) were analyzed. Fibrinogen levels were determined within 3 hours (STAT) or 6 hours (ESTAT) of stroke onset and at preset intervals throughout 5 days of intravenous infusions. Barthel Index scores at 90 days quantified functional outcomes. The association between initial fibrinogen levels and functional outcomes was evaluated using a multiple logistic regression analysis.

Results—Fibrinogen levels increased gradually over the first 24 hours from a pretreatment median value of 340 mg/dL to a 24-hour median value of 376 mg/dL. In a univariate analysis, the proportion of patients with good functional outcome decreased with increasing quartiles of initial fibrinogen levels in both STAT (36.0% to 26.2%) and ESTAT (53.8% to 24.8%). In a multifactorial analysis, the same trend was observed. Patients with initial fibrinogen levels <450 mg/dL had better outcomes in both studies; the difference (42.0% versus 21.6%) was significant in ESTAT (P=0.0006), even when corrected for age and initial stroke severity.

Conclusion—The independent association of higher initial fibrinogen levels with poor outcome needs to be verified using a larger acute stroke dataset. Even in the present small populations, the apparent association of these 2 variables suggests that treatments designed to reduce fibrinogen levels could potentially be important in treating acute ischemic stroke.

Key words: fibrinogen • functional outcome • defibrinogenation • acute ischemic stroke

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Mario Di Napoli and Puneetpal Singh
Stroke 2009 40: 1549-1552. [Extract] [Full Text] [PDF]

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