Study of Correlation Between Hp α1 Expression of Haptoglobin 2-1 and Clinical Course in Aneurysmal Subarachnoid Hemorrhage

BACKGROUND: Haptoglobin (Hp) comprising 2 light (a) and 2 heavy (b) chains has an antioxidant effect following free hemoglobin binding. Among 3 phenotypes-Hp1-1 (two alpha 1), Hp2-1 (alpha 1 and alpha 2), and Hp2-2 (two alpha 2)-a greater protective effect for toxic-free hemoglobin was reported for Hp2-2 compared with Hp1-1. However, few studies have focused on the association of Hp2-1 with outcomes. This study examined alpha 1 and alpha 2 expression, and evaluated the correlation of Hp2-1 with outcomes of subarachnoid hemorrhage (SAH). METHODS: Eighty-seven patients were enrolled prospectively, including 12 in the Hp1-1 group (13.8%), 36 in the Hp2-1 group (41.4%), and 39 in the Hp2-2 group (44.8%). Phenotypes were confirmed by Western blot analysis. The relative band intensities were measured as a subunit intensities normalized to albumin intensities and expressed as median (interquartile range). The differences in a intensities according to delayed cerebral ischemia (DCI), angiographic vasospasm (AV), and outcome were analyzed. RESULTS: DCI and AV were more frequently associated with Hp2-2 than with Hp1-1 (DCI: 21 [53.8%] vs. 3 [25.0%]; AV: 22 [56.4%] vs. 3 [25.0%]). The alpha 1 intensities of Hp2-1 without DCI and AV were significantly higher than those with DCI and AV (without DCI: 0.70 [interquartile range (IQR), 0.54-0.89]; with DCI: 0.24 [IQR, 0.14e0.32]; P < 0.001; without AV: 0.65 [IQR, 0.32-0.88]; with AV: 0.32 [IQR, 0.17-0.67]; P = 0.046). No significant difference was noted with alpha 2 intensities. The alpha 1 (P = 0.359) and alpha 2 (P = 0.233) intensities did not differ significantly according to outcome. CONCLUSIONS: Higher alpha 1 intensities in Hp2-1 are associated with a lower risk of DCI and AV. The degree of alpha 1 intensity may provide additional information about the individual risk of secondary injury following SAH in patients with Hp2-1.