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

Background: Haptoglobin (Hp) comprising 2 light (α) and 2 heavy (β) chains has an antioxidant effect following free hemoglobin binding. Among 3 phenotypes-Hp1-1 (two α1), Hp2-1 (α1 and α2), and Hp2-2 (two α2)-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 α1 and α2 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 α subunit intensities normalized to albumin intensities and expressed as median (interquartile range). The differences in α 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 α1 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, 0.14-0.32]; 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 α2 intensities. The α1 (P = 0.359) and α2 (P = 0.233) intensities did not differ significantly according to outcome.

Conclusions: Higher α1 intensities in Hp2-1 are associated with a lower risk of DCI and AV. The degree of α1 intensity may provide additional information about the individual risk of secondary injury following SAH in patients with Hp2-1.