Early plasma complement C3a levels correlate with functional outcome after aneurysmal subarachnoid hemorrhage

Studies have documented an inflammatory response in the circulating plasma and cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage (aSAH). In particular, early upregulation of several complement proteins, including C3a, C4a, and C5b-9, has been demonstrated after the initial hemorrhagic insult. The inflammatory actions of the complement cascade are largely mediated through the anaphylatoxins, C3a and C5a. Recent investigations have established a critical role for C3a in the pathogenesis of cerebral ischemia. We attempt to confirm that plasma C3a and C5a values are elevated in patients with aSAH and to determine whether or not these levels are reliable independent predictors of functional outcome irrespective of clinical presentation.

Fifty-two patients with aSAH were prospectively enrolled and stratified according to admission Hunt and Hess grade, demographic variables, and functional status at the time of discharge (modified Rankin Scale score). Plasma C3a and C5a levels were determined at early and late time points after aSAH through enzyme-linked immunosorbent assay.

After aSAH, early C3a and C5a values were increased compared with levels in non-SAH control patients (P < 0.001). Univariate analysis demonstrated that elevations in early C3a (P = 0.010) and C5a (P = 0.041) levels and poor admission Hunt and Hess grade (P = 0.015) correlated significantly with unfavorable outcome. In our multivariate model, only early C3a levels retained a strong correlation with outcome when modeled with Hunt and Hess grade (P = 0.009).

These results demonstrate an association between early complement C3a levels and outcome after aSAH that seems to be independent of the initial hemorrhage. The findings suggest that inflammatory processes involving C3a may contribute to delayed morbidity and mortality after aneurysmal rupture.