Cottarelli Azzurra, Mamoon Rayan, Ji Robin, Mao Eric, Boehme Amelia, Kumar Aditya, Song Sandy, Allegra Valentina, Sharma Sabrina V, Konofagou Elisa, Spektor Vadim, Guo Jia, Connolly E Sander, Sekar Padmini, Woo Daniel, Roh David J
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
bioRxiv. 2024 Aug 19:2024.08.15.608155. doi: 10.1101/2024.08.15.608155.
Although lower hemoglobin levels associate with worse intracerebral hemorrhage (ICH) outcomes, causal drivers for this relationship remain unclear. We investigated the hypothesis that lower hemoglobin relates to increased hematoma expansion (HE) risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH.
ICH patients with baseline hemoglobin measurements and serial CT neuroimaging enrolled between 2010-2016 to a multicenter, prospective observational cohort study were studied. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with HE (≥33% and/or ≥6mL growth) and poor long-term neurological outcomes (modified Rankin Scale 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic vs. non-anemic C57/BL6 mice, intergroup differences in ICH lesion volume, ICH volume changes, and early mortality were assessed.
Among 1190 ICH patients analyzed, lower baseline hemoglobin levels associated with increased odds of HE (adjusted OR per -1g/dL hemoglobin decrement: 1.10 [1.02-1.19]) and poor 3-month clinical outcomes (adjusted OR per -1g/dL hemoglobin decrement: 1.11 [1.03-1.21]). Similar relationships were seen with poor 6 and 12-month outcomes. In our animal model, anemic mice had significantly greater ICH lesion expansion, final lesion volumes, and greater mortality, as compared to non-anemic mice.
These results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in HE and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.
尽管较低的血红蛋白水平与脑出血（ICH）预后较差相关，但这种关系的因果驱动因素仍不清楚。我们使用人类观察数据研究了较低血红蛋白与血肿扩大（HE）风险增加和预后不良相关的假设，并使用贫血和ICH的转化小鼠模型评估因果关系。
研究了2010年至2016年间纳入多中心前瞻性观察队列研究的有基线血红蛋白测量值和系列CT神经影像学检查的ICH患者。排除有全身性凝血病证据的患者。在调整相关协变量后，采用单独的回归模型评估基线血红蛋白与HE（≥33%和/或≥6mL增长）及长期神经功能不良预后（改良Rankin量表4-6级）之间的关系。在贫血与非贫血的C57/BL6小鼠中使用小鼠胶原酶ICH模型并进行系列神经影像学检查，评估组间ICH病变体积、ICH体积变化和早期死亡率的差异。
在分析的1190例ICH患者中，较低的基线血红蛋白水平与HE几率增加（每降低1g/dL血红蛋白调整后的OR：1.10[1.02-1.19]）和3个月临床预后不良（每降低1g/dL血红蛋白调整后的OR：1.11[1.03-1.21]）相关。在6个月和12个月预后不良方面也观察到类似关系。在我们的动物模型中，与非贫血小鼠相比，贫血小鼠的ICH病变扩大、最终病变体积明显更大，死亡率更高。
这些在人类队列和小鼠模型中的结果提供了新的证据，表明贫血在HE和ICH不良预后中起因果作用。需要进一步研究以阐明纠正贫血是否能改善这些预后。
