Hemostasis, Hematoma Expansion, and Outcomes After Intracerebral Hemorrhage

项目总结 脑出血(ICH)是中风最危险的形式，目前还没有得到美国批准的治疗方法 美国食品和药物管理局。血肿扩大(HE)，即血肿的间歇性生长，是近端的一种 由于较大的血肿取代脑组织，导致较差的患者预后和死亡的原因；血肿和60毫升 在随访时可靠地导致残疾或死亡。预防HE是改善预后的有希望的策略 脑出血患者。然而，我们相对无法预测HE，阻碍了有效的 脑出血的治疗策略，以及几项临床试验都未获成功。即使当他已经 降低，我们发现益处的能力受到相对不敏感的患者结果的阻碍。这项提议将 解决阻碍开发有效治疗脑出血的两个障碍，脑出血是最病态的 卒中。 三个综合性中风中心(两个来自伊利诺伊州芝加哥的西北医学系统， 和德克萨斯大学休斯顿分校)将合作伙伴，前瞻性地招募脑出血患者，测量 止血，测量HE，并使用包括NIH在内的最先进的评估记录患者结果 患者报告结果测量信息系统(PROMIS)和NIH工具箱。 首先，我们将确定在急性脑出血中导致HE的机制，大致分为血小板活性， 激活凝血和纤溶。每一种都可以具体测量，并有专门的治疗方法 改进它。例如，使用去氨加压素可以可靠地改善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，纤溶加速可能是 用氨甲环酸或氨基己酸还原。将检查每一个以预测HE；如果有多个 找到了路径，我们将确定哪些是机器学习中最重要的。曾经最多的 HE的重要止血机制已确定，我们将探索具体治疗是否有所改善 血小板活性。针对特定止血缺陷的特定治疗方法可能更有可能 与一般应用于脑出血患者的单一疗法相比，降低HE(例如，第VII因子)。 一旦确定了HE的止血机制，我们将确定HE对患者预后的影响 例如修正的Rankin量表(MRS，全球序数量表)、PROMIS和NIH工具箱。这将是 对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情况来改善患者的结果 急性脑出血的止血治疗。结果将广泛适用于其他出血情况(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).