Hemorrhage control in the irreversible anticoagulated patient

不可逆抗凝患者的出血控制

• 批准号: 9489300
• 负责人: Rahmi Oklu
• 金额: $ 59.43万
• 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/9489300
• 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; Injections; 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; cardiac device; 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).

项目摘要/摘要 抗凝设置（ACA）的出血是与高有关的严重医疗紧急情况 发病率和死亡率。机械阀或心脏辅助设备（CAD）的ACA患者 出血的风险更大，因为这些患者可能无法进行ACA逆转。这些患者 通常被认为是高风险的开放手术修复，今天更常见 血管内方法。例如，胃肠道出血（GIB），是最常见的形式之一 当今ACA患者中看到的内部出血和威胁生命的医疗紧急情况，会影响 在美国，每年约有500,000名患者。实际上，研究表明，多达40％的GIB 遵循CAD植入物（AA）。如果发生出血，死亡率的率将从10％急剧增加到40％ 在住院治疗另一种疾病期间，尤其是当ACA复杂时。在过去的30年中，开放 GIB的手术治疗已被微创内血管内干预所取代。这 方法涉及跨出出血部位的金属线圈的传递；这些线圈诱导血栓形成 阻塞船只。但是，线圈栓塞存在明显的缺点。最重要的是经常性 在无法产生的抗凝和凝血病患者中出血或持续出血 血栓。当线圈栓塞后发生重新出血或爆发出血时，死亡的风险 增加10倍（6）。我们通过使用尖端的现成的注射止血来假设这一点 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出血的患者 抗凝或凝血病（即散布的血管内凝血（DIC））。我们的新方法 使用通用剪切的生物材料（STB），该生物材料（STB）可产生令人难以置信的出血容器 不依靠血栓形成以获得功效。在此提案中，我们将进一步优化三个候选STB 配方（目标1），在体外和离体动脉模型中测试它们（AIM 2），并最终评估 STB在栓塞抗凝猪模型中的性能（AIM 3）。