Departments of Neurology, Anesthesiology Critical Care Medicine and Neurosurgery, Johns Hopkins Hospital, Neurosciences Critical Care Division, Baltimore MD, USA.
Division of Brain Injury Outcomes, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Int J Stroke. 2020 Oct;15(8):899-908. doi: 10.1177/1747493020912602. Epub 2020 Apr 7.
Perihematomal edema in intracranial hemorrhage is influenced by free hemoglobin clearance and inflammation. Serum Haptoglobin (Hp) binds free hemoglobin, affecting heme clearance and free radical production. Of the three Hp phenotypes, Hp 1-1 has the greatest effect on free hemoglobin clearance.
To determine if individuals with Hp 1-1 phenotype have different rates of early perihematomal edema formation as compared to those with Hp 2-1 and Hp 2-2.
We determined Hp phenotype, intracranial hemorrhage volume, and rate of early change in perihematomal volume in participants from three prospectively collected intracranial hemorrhage cohorts. The association of Hp phenotypes 1-1, 2-1, 2-2, with early change in perihematomal volume, while controlling for key clinical characteristics was analyzed using a multivariate model.
One-hundred and sixty-six participants were included: 73 (44%) female, 41 ( 25%) African Americans, 34 (20%) diabetics, 133 (80%) with hypertension, and 75 (45%) active smokers. There were 15 subjects with Hp phenotype 1-1, 86 with 2-1, and 65 with 2-2. In fully adjusted analysis, Hp 1-1 had a significantly increased estimated mean rate of early change in perihematomal volume at 1.15 (95% confidence interval 0.58-1.71) as compared to all other Hp 2-1 or Hp 2-2 containing phenotypes (0.30, 95% confidence interval 0.06-0.54; 0.29 95% CI 0.02-0.56). Neither mortality nor discharge mRS differed between Hp phenotypes.
Haptoglobin phenotype is associated with early change in perihematomal volume. Hp 1-1 phenotype had significantly increased mean rate of early change in perihematomal volume within the first 96 h, suggesting that haptoglobin phenotype may be a key player in understanding the multiphasic progression of perihematomal volume in spontaneous intracerebral hemorrhage. A larger prospective observational study is warranted.
颅内出血的血肿周围水肿受游离血红蛋白清除和炎症的影响。血清结合珠蛋白（Hp）结合游离血红蛋白，影响血红素清除和自由基生成。在三种 Hp 表型中，Hp 1-1 对游离血红蛋白清除的影响最大。
确定 Hp 1-1 表型个体与 Hp 2-1 和 Hp 2-2 个体相比，是否具有不同的早期血肿周围水肿形成率。
我们在三个前瞻性收集的颅内出血队列的参与者中确定了 Hp 表型、颅内出血体积和血肿周围体积早期变化率。使用多元模型分析 Hp 表型 1-1、2-1、2-2 与早期血肿周围体积变化的相关性，同时控制关键临床特征。
共纳入 166 名参与者：73 名（44%）为女性，41 名（25%）为非裔美国人，34 名（20%）为糖尿病患者，133 名（80%）为高血压患者，75 名（45%）为吸烟者。15 名受试者为 Hp 表型 1-1，86 名受试者为 2-1，65 名受试者为 2-2。在完全调整的分析中，与所有其他 Hp 2-1 或 Hp 2-2 表型相比，Hp 1-1 的血肿周围体积早期变化的估计平均率显著增加，为 1.15（95%置信区间为 0.58-1.71）（0.30，95%置信区间为 0.06-0.54；0.29 95%CI 0.02-0.56）。在 Hp 表型之间，死亡率或出院 mRS 无差异。
结合珠蛋白表型与血肿周围体积的早期变化有关。Hp 1-1 表型在最初 96 小时内血肿周围体积早期变化的平均率显著增加，这表明结合珠蛋白表型可能是理解自发性脑出血血肿周围体积多相进展的关键因素。需要更大的前瞻性观察研究。
