WARSS-HEMOSTATIC SYSTEM ACTIVATION SUBSTUDY (WARSS/HAS)

WARSS-止血系统激活子研究（WARSS/HAS）

• 批准号: 2519964
• 负责人: J P KISTLER
• 金额: $ 10.51万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2519964
• 关键词: aspirin; cardiovascular disorder chemotherapy; cardiovascular disorder epidemiology; cerebral ischemia /hypoxia; disease /disorder proneness /risk; drug resistance; fibrinogen; hemostatics; human subject; human therapy evaluation; longitudinal human study; prothrombin; stroke; thrombin; thromboembolism; warfarin

The aims of this study are to determine the level of activity of the hemostatic system (in vivo thrombin generation) in patients who have suffered a previous ischemic stroke. We will measure the plasma level of the prothrombin activation fragment Fl+2, in a representative subset of patients in the Warfarin Aspirin Recurrent Stroke Study (WARSS - NINDS 5 R0l NS2837I). In that study, patients who have suffered a "cryptogenic" (embolic) stroke are assigned to either antithrombotic or antiplatelet therapy. The treatment arms consist of warfarin to maintain INR between 1.4 and 2.8, or aspirin at 325 mg/day. For this substudy of WARSS, we hypothesize that Patients with previous embolic stroke will have a higher level of Fl+2 than patients with other types of ischemic stroke. We will determine whether prothrombin fragment Fl+2 is lowered to a greater extent by warfarin than by aspirin in the embolic "cryptogenic" group of patients as compared to patients in the other stroke groups (atherothrombotic, tandem arterial pathology, small vessel/lacunar). In addition to prothrombin fragment Fl+2 and INR, we will measure serum fibrinogen, albumin/globulin ratios and complete blood counts. To determine whether the relationships between the various parameters are stable over time, plasma samples will be obtained every six months for 2.5 years. Our proposed studies provide the opportunity to answer the following questions: (a) is there a particular group of patients that have a higher level of prothrombin generation?; (b) is there a particular subgroup of patients who are resistant to warfarin-induced thrombin generation?; (c) if warfarin is effective in preventing secondary stroke at the target INR, what is the relation between INR and Fl+2?; and (d) are these relationships stable over time?

本研究的目的是确定 止血系统（体内凝血酶生成）患者 既往患有缺血性中风。 我们将测量血浆水平 凝血酶原激活片段 Fl+2，在一个代表性子集中 华法林阿司匹林复发性中风研究 (WARSS - NINDS 5 R0l NS2837I)。 在那项研究中，患有“隐源性疾病”的患者 （栓塞性）中风分为抗血栓药物或抗血小板药物 治疗。 治疗组包含华法林，以将 INR 维持在 1.4 和 2.8，或阿司匹林 325 毫克/天。 对于 WARSS 的这项子研究，我们 假设既往有栓塞性中风的患者的死亡率会更高 Fl+2 水平高于其他类型的缺血性中风患者。 我们将 确定凝血酶原片段Fl+2是否降低程度更大 在“隐源性”栓塞患者组中，华法林治疗优于阿司匹林治疗 与其他中风组（动脉粥样硬化、 串联动脉病理学，小血管/腔隙）。 此外 凝血酶原片段 Fl+2 和 INR，我们将测量血清纤维蛋白原， 白蛋白/球蛋白比率和全血细胞计数。 判断是否 各种参数之间的关系随着时间的推移是稳定的， 血浆样本将在 2.5 年内每六个月采集一次。 我们提出的研究提供了回答以下问题的机会 问题：(a) 是否有一组特定的患者具有较高的 凝血酶原生成水平？； (b) 是否存在一个特定的子组 对华法林诱导的凝血酶产生有抵抗力的患者？ (三) 如果华法林在目标 INR 下能有效预防继发性中风， INR 和 Fl+2 之间有什么关系？ (d) 这些是 随着时间的推移关系稳定吗？