Hemorrhage control in the irreversible anticoagulated patient

不可逆抗凝患者的出血控制

• 批准号: 9301809
• 负责人: Rahmi Oklu
• 金额: $ 61.43万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9301809
• 关键词: Affect; Angiography; Animal Model; Anticoagulation; Arteries; Biocompatible Materials; Blood Coagulation Disorders; Blood Coagulation Factor; Blood Vessels; Cardiac; Catheters; Clinical; Complex; Data; Devices; Disseminated Intravascular Coagulation; Emergency Situation; Endothelial Cells; Endothelium; Engineering; Etiology; Family suidae; Formulation; Gastrointestinal Hemorrhage; Gastrointestinal tract structure; Hemorrhage; Hemostatic Agents; Heparin; Histology; Hospitalization; Imagery; Immune response; In Vitro; Inflammatory; Injectable; Injection of therapeutic agent; Intervention; Lead; Life; Mechanics; Medical; Medical emergency; Modeling; Monitor; Morbidity - disease rate; Operative Surgical Procedures; Patients; Performance; Physiological; Property; Rattus; Recurrence; Resources; Risk; Safety; Site; Source; Stroke; Structure of internal iliac artery; Testing; Therapeutic Embolization; Thinness; Thrombosis; Thrombus; Time; Ultrasonography; Warfarin; X-Ray Computed Tomography; artery occlusion; base; biomaterial compatibility; cost; elastomeric; femoral artery; high risk; iliac artery; implantable device; in vivo; interdisciplinary approach; metallicity; minimally invasive; mortality; novel strategies; repaired

Project Summary/Abstract Hemorrhage in a setting of anticoagulation (ACA) is a serious medical emergency associated with high morbidity and mortality. Patients on ACA for mechanical valves or cardiac assist devices (CAD) and who are bleeding are at even greater risk because ACA reversal may not be possible in these patients. These patients are typically considered to be high-risk for open surgical repair and are more commonly treated today by endovascular approaches. For example, gastrointestinal bleeding (GIB), one of the most common forms of internal hemorrhage and life-threatening medical emergencies seen in the ACA patient today, affects approximately 500,000 patients annually in the US. In fact, studies have shown that up to 40% develop GIB following CAD implant (AA). The rate of mortality drastically increases from 10% to 40% if bleeding occurs during a hospitalization for another illness, especially when complicated by ACA. Over the past 30 years, open surgical treatment of GIB has been largely replaced by minimally invasive endovascular interventions. This approach involves delivery of metallic coils spanning the bleeding site; these coils induce thrombosis to occlude the vessel. However, there are significant drawbacks to coil embolization; most important is recurrent bleeding or persistent bleeding in anticoagulated and in coagulopathy patients who are unable to produce a thrombus. When re-bleeding or break-through bleeding occurs following coil embolization, risk of mortality increases 10-fold (6). We hypothesize that by using a cutting-edge off-the-shelf injectable hemostatic biomaterial, we can reduce morbidity/mortality; and for the first time, we can treat bleeding patients that are on anticoagulation or are coagulopathic (i.e., disseminated intravascular coagulation (DIC)). Our novel approach uses a universal shear-thinning biomaterial (STB) that creates an impenetrable cast of the bleeding vessel without relying on thrombosis for efficacy. In this proposal, we will further optimize the three candidate STB formulations (Aim 1), test them in in vitro and ex vivo artery models (Aim 2) and finally evaluate the performance of the STBs in the anticoagulated porcine models of embolization (Aim 3).

项目概要/摘要 抗凝治疗 (ACA) 中的出血是一种严重的医疗紧急情况，与高血脂相关 发病率和死亡率。因机械瓣膜或心脏辅助装置 (CAD) 而接受 ACA 治疗的患者 出血的风险更大，因为这些患者可能无法实现 ACA 逆转。这些患者 通常被认为是开放式手术修复的高风险，目前更常见的治疗方法是 血管内方法。例如，胃肠道出血 (GIB)，这是最常见的出血形式之一。 今天在 ACA 患者中看到的内出血和危及生命的医疗紧急情况，影响 美国每年约有 500,000 名患者。事实上，研究表明高达 40% 的人患有 GIB CAD 植入 (AA) 后。如果发生出血，死亡率会从 10% 急剧增加至 40% 因另一种疾病住院期间，尤其是并发 ACA 时。 30年来，开放 GIB的手术治疗已很大程度上被微创血管内介入治疗所取代。这 方法包括递送金属线圈跨越出血部位；这些线圈会诱发血栓形成 闭塞血管。然而，线圈栓塞也有明显的缺点；最重要的是反复出现 抗凝治疗和无法产生凝血功能的凝血病患者出血或持续出血 血栓。当弹簧圈栓塞后发生再出血或突破性出血时，存在死亡风险 增加 10 倍 (6)。我们假设通过使用尖端的现成注射止血剂 生物材料，我们可以降低发病率/死亡率；我们第一次可以治疗正在接受治疗的出血患者 抗凝或凝血障碍（即弥散性血管内凝血 (DIC)）。我们的新颖方法 使用通用剪切稀化生物材料 (STB) 打造难以穿透的出血血管模型 不依赖血栓形成来发挥功效。在本提案中，我们将进一步优化三个候选机顶盒 配方（目标 1），在体外和离体动脉模型中进行测试（目标 2），最后评估 STB 在抗凝猪栓塞模型中的性能（目标 3）。