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(Stroke. 2008;39:3236.)
© 2008 American Heart Association, Inc.

Original Contributions

Platelet C4d Is Associated With Acute Ischemic Stroke and Stroke Severity

Nidhi Mehta, MD; Ken Uchino, MD; Saeed Fakhran, MD; M. Abdus Sattar, MS; Barton F. Branstetter, IV, MD; Karen Au, MD; Jeannine S. Navratil, MS; Barbara Paul, Med; Melissa Lee; Katie M. Gallagher, MS; Susan Manzi, MD, MPH; Joseph M. Ahearn, MD Amy H. Kao, MD, MPH

From the University of Pittsburgh School of the Health Sciences (N.M., K.U., S.F., B.F.B., K.A., J.S.N., B.P., M.L., K.M.G., S.M., J.M.A., A.H.K.), the University of Pittsburgh Graduate School of Public Health (M.A.S., S.M.), and the Lupus Center of Excellence (J.S.N., B.P., K.M.G., S.M., J.M.A., A.H.K.), University of Pittsburgh, Pa.

Correspondence to Amy H. Kao, MD, MPH, S721 Biomedical Science Tower, 3500 Terrace Street, Pittsburgh, PA 15261. E-mail ahk7{at}pitt.edu

Background and Purpose— Platelets bearing complement C4d were recently reported to be 99% specific for a diagnosis of systemic lupus erythematosus (SLE) and associated with neuropsychiatric lupus. We compared the prevalence of platelet C4d and investigated the clinical associations of platelet C4d in patients with acute ischemic stroke.

Methods— We recruited 80 patients hospitalized for acute ischemic stroke. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIH-SS). Infarct volume was determined by MRI. Platelet C4d was measured by flow cytometry.

Results— Mean age was 57.9 years (range: 24.6 to 86.8 years), 58% were male, and 91% were white. Eight patients (10%) with acute ischemic stroke were platelet C4d-positive, which was significantly higher in prevalence compared to healthy controls (0%, P<0.0001) and non-SLE patients with immune/inflammatory disease (2%, P=0.004). The median NIH-SS score and infarct volume for acute stroke patients were 6 (interquartile range [IQR]: 2 to 13) and 3.4 cc (IQR: 1.1 to 16.6), respectively. Platelet C4d-positive patients were more likely to have a severe stroke compared to those with negative platelet C4d (NIH-SS median: 17.5 versus 5, P=0.003). Positive platelet C4d was independently associated with stroke severity (P=0.03) after controlling for age, anticardiolipin antibody (aCL) status, and total anterior circulation of stroke involvement, and also with infarct volume (P=0.005) after controlling for age, aCL status, and old stroke by MRI.

Conclusions— Platelet C4d is associated with severe acute ischemic stroke. Platelet C4d may be a biomarker as well as pathogenic clue that links cerebrovascular inflammation and thrombosis.

Key Words: complement activation • platelet • ischemic stroke • stroke severity • infarct volume • NIH stroke scale

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