Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage
Haptoglobin phenotype predicts the development of focal and global cerebral vasospasm and may influence outcomes after aneurysmal subarachnoid hemorrhage
复制标题
DOI：
10.1073/pnas.1412833112
复制
发表时间：
2015-01-27
影响因子：
11.1
通讯作者：
Dore, Sylvain
中科院分区：
文献类型：
--
作者：
Leclerc, Jenna L.;Blackburn, Spiros;Dore, Sylvain
脑血管痉挛（CV）和由此导致的迟发性脑缺血（DCI）显着导致动脉瘤性蛛网膜下腔出血（aSAH）后的不良预后。蛛网膜下腔内的游离血红蛋白 (Hb) 与 CV 的发病机制有关。触珠蛋白 (Hp) 结合游离的促氧化剂 Hb，从而调节其有害作用。人类可以具有三种 Hp 表型：Hp1-1、Hp2-1 或 Hp2-2。在多种疾病状态下，Hp2-2 蛋白与抵御无毒 Hb 的能力降低有关。我们假设具有 Hp2-2 表型的个体在 aSAH 后会有更高的 CV、DCI、死亡率和更差的功能结果。在 74 名 aSAH 患者的样本中，控制协变量后，Hp2-2 表型与局部中度 (P = 0.014) 和重度 (P = 0.008) CV 以及更多整体 CV (P = 0.014) 的增加显着相关。对于 Hp2-2 患者，在 6 周（P = 0.076）和 1 年（P = 0.051）时采用改良 Rankin 量表，以及在出院时（P = 0.091）和 1 年（P = 0.055）扩展格拉斯哥结果量表（P = 0.055）时，死亡率增加（P = 0.079）和功能结果较差的趋势明显。总之，Hp2-2 表型是局灶性和整体 CV 发生的独立危险因素，也可预测 aSAH 后不良的功能结果和死亡率。 Hp 表型分析可以作为 aSAH 患者重症监护管理中临床上有用的工具，通过允许早期预测那些由于其发生 CV 和由此产生的 DCI 和不良预后的固有遗传风险而需要提高警惕的患者。
Cerebral vasospasm (CV) and the resulting delayed cerebral ischemia (DCI) significantly contribute to poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH). Free hemoglobin (Hb) within the subarachnoid space has been implicated in the pathogenesis of CV. Haptoglobin (Hp) binds free pro-oxidant Hb, thereby modulating its harmful effects. Humans can be of three Hp phenotypes: Hp1-1, Hp2-1, or Hp2-2. In several disease states, the Hp2-2 protein has been associated with reduced ability to protect against toxic free Hb. We hypothesized that individuals with the Hp2-2 phenotype would have more CV, DCI, mortality, and worse functional outcomes after aSAH. In a sample of 74 aSAH patients, Hp2-2 phenotype was significantly associated with increased focal moderate (P = 0.014) and severe (P = 0.008) CV and more global CV (P = 0.014) after controlling for covariates. Strong trends toward increased mortality (P = 0.079) and worse functional outcomes were seen for the Hp2-2 patients with modified Rankin scale at 6 wk (P = 0.076) and at 1 y (P = 0.051) and with Glasgow Outcome Scale Extended at discharge (P = 0.091) and at 1 y (P = 0.055). In conclusion, Hp2-2 phenotype is an independent risk factor for the development of both focal and global CV and also predicts poor functional outcomes and mortality after aSAH. Hp phenotyping may serve as a clinically useful tool in the critical care management of aSAH patients by allowing for early prediction of those patients who require increased vigilance due to their inherent genetic risk for the development of CV and resulting DCI and poor outcomes.