Hemorrhage control in the irreversible anticoagulated patient

项目摘要/摘要 抗凝环境中的出血(ACA)是一种严重的医疗急症，与高血压病有关。 发病率和死亡率。使用机械瓣膜或心脏辅助装置(CAD)的ACA患者，以及 出血的风险更大，因为这些患者可能无法逆转ACA。这些病人 通常被认为是开放手术修复的高风险，现在更常见的是通过 血管内途径。例如，胃肠道出血(GIB)，最常见的形式之一 今天ACA患者出现的内出血和危及生命的医疗紧急情况影响到 在美国，每年大约有50万名患者。事实上，研究表明，高达40%的人会患上GIB 冠脉种植术后(AA)。如果发生出血，死亡率会从10%急剧增加到40%。 在另一种疾病住院期间，尤指并发ACA时。过去30年，开放 外科治疗GIB在很大程度上已被微创血管内介入治疗所取代。这 方法涉及跨越出血部位的金属弹簧圈的输送；这些弹簧圈导致血栓形成 堵住血管。然而，弹簧圈栓塞术有很大的缺点；最重要的是复发。 抗凝血患者和凝血障碍患者的出血或持续性出血 血栓。当弹簧圈栓塞术后再次出血或穿透出血时，死亡风险 增加10倍(6)。我们假设通过使用尖端现成的可注射止血剂 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出血的病人。 抗凝或凝血异常(即弥散性血管内凝血(DIC))。我们的新方法 使用一种通用的剪切变薄生物材料(STB)，使出血的血管形成无法穿透的管型 而不依赖血栓形成的疗效。在这份提案中，我们将进一步优化三个候选机顶盒 制剂(目标1)，在体外和体外动脉模型(目标2)中测试它们，最后评估 STBS在抗凝猪栓塞术模型中的性能(目标3)。

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).