Hemostasis, Hematoma Expansion, and Outcomes After Intracerebral Hemorrhage

项目摘要 脑出血（ICH）是最常见的卒中形式，目前尚无美国批准的治疗方法 食品药品监督管理总局.血肿扩张（HE），血肿的间隔生长，是一种近似的 患者结局更差和死亡的原因，因为较大血肿移位脑组织;血肿> 60 mL 在随访时可靠地导致残疾或死亡。预防HE是一种很有前途的策略，可以改善 ICH患者。然而，我们相对无法预测HE，这阻碍了有效治疗的发展。 ICH的治疗策略，并且一些临床试验一直不成功。即使他已经 降低，我们检测益处的能力受到相对不敏感的患者结果的阻碍。这项建议会 解决了两个阻碍发展有效治疗脑出血的障碍，脑出血是最病态的脑出血形式。 中风 三个综合性中风中心（两个来自伊利诺斯州大都市芝加哥的西北医学系统， 和德克萨斯大学休斯顿分校）将合作前瞻性招募ICH患者， 止血，测量HE，并使用最新技术水平评估记录患者结局，包括NIH 患者报告结果测量信息系统（PROMIS）和NIH。 首先，我们将确定导致急性ICH HE的机制，大致分为血小板活性， 激活凝血和纤维蛋白溶解。每一种都可以具体测量，并有具体的治疗方法， 例如，去氨加压素可以可靠地改善由于阿司匹林引起的血小板活性降低， 凝血激活延迟可能与低镁血症有关，纤维蛋白溶解加速可能与低镁血症有关。 用氨甲环酸或氨基己酸还原。将检查每一项以预测HE;如果有多项 找到路径后，我们将确定哪些是机器学习最重要的。曾经最 确定HE止血的重要机制后，我们将探索是否有特异性治疗改善 血小板活性针对特定止血缺陷的特定治疗可能更有可能 比通常应用于ICH患者的单一疗法减少HE（例如，因子VII）。 一旦确定了HE的止血机制，我们将确定HE对患者结局的影响 如改良的兰金量表（mRS，一种整体顺序量表）、PROMIS和NIH量表。这将是 对于计划未来的临床试验至关重要，这些试验旨在通过纠正异常 急性ICH止血。结果将广泛适用于其他出血性疾病（例如，神经创伤）。

PROJECT SUMMARY Intracerebral hemorrhage (ICH) is the most morbid form of stroke and has no treatment approved by the US Food and Drug Administration. Hematoma expansion (HE), interval growth of the hematoma, is a proximate cause of worse patient outcomes and death as larger hematomas displace brain tissue; hematomas > 60 mL reliably lead to disability or death at follow-up. Preventing HE is a promising strategy to improve outcomes for patients with ICH. Our relative inability to predict HE, however, has impeded the development of effective treatment strategies for ICH, and several clinical trials have been unsuccessful. Even when HE has been reduced, our ability to detect a benefit is hampered by relatively insensitive patient outcomes. This proposal will resolve two roadblocks that prevent the development of effective treatments for ICH, the most morbid form of stroke. Three comprehensive stroke centers (two from the Northwestern Medicine system in metropolitan Chicago, IL, and the University of Texas at Houston) will partner to prospectively enroll patients with ICH, measure hemostasis, measure HE, and record patient outcomes with state of the art assessments, including the NIH Patient Reported Outcomes Measurement Information System (PROMIS) and NIH Toolbox. First, we will determine the mechanisms that lead to HE in acute ICH, broadly grouped into platelet activity, activation of coagulation, and fibrinolysis. Each can be specifically measured and has specific treatments to improve it. For example, reduced platelet activity due to aspirin can be reliably improved with desmopressin, delayed activation of coagulation may be related to hypomagnesemia, and accelerated fibrinolysis may be reduced with tranexamic acid or aminocaproic acid. Each will be examined for predicting HE; if multiple pathways are found, we will determine which are most important with machine learning. Once the most important mechanisms of hemostasis for HE are determined, we will explore if specific therapies improve platelet activity. It is possible that specific treatments for specific deficits in hemostasis will be more likely to reduce HE than single therapies applied to ICH patients generally (e.g., Factor VII). Once hemostatic mechanisms of HE are determine, we will determine the effect of HE on patient outcomes such as the modified Rankin Scale (mRS, a global ordinal scale), PROMIS, and NIH Toolbox. This will be crucial to plan for future clinical trials intended to improve patient outcomes through correcting abnormal hemostasis in acute ICH. Results will apply broadly to other bleeding conditions (e.g., neurotrauma).