Hemorrhage control in the irreversible anticoagulated patient

项目概要/摘要 抗凝治疗中出血（ACA）是一种严重的医疗紧急情况， 发病率和死亡率。接受ACA治疗机械瓣膜或心脏辅助装置（CAD）的患者， 出血的风险更大，因为ACA逆转在这些患者中可能是不可能的。这些患者 通常被认为是开放手术修复的高风险，目前更常见的治疗方法是 血管内方法。例如，胃肠道出血（GIB），最常见的胃肠道出血形式之一， 内出血和危及生命的医疗紧急情况中看到的ACA患者今天，影响 在美国每年约有50万患者。事实上，研究表明，高达40%的GIB CAD植入后（AA）。如果发生出血，死亡率从10%急剧增加到40%。 在住院治疗另一种疾病，特别是当并发ACA。30年来，开放 GIB的外科治疗已在很大程度上被微创血管内介入所取代。这 一种方法涉及跨越出血部位的金属线圈的输送;这些线圈诱导血栓形成， 堵塞血管然而，弹簧圈栓塞也有明显的缺点，最重要的是复发性 抗凝和凝血病患者中的出血或持续出血， 血栓当弹簧圈栓塞后发生再出血或突破性出血时， 增加10倍（6）。我们假设通过使用最先进的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;第一次，我们可以治疗出血患者， 抗凝或凝血病（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致稀生物材料（STB）， 而不依赖于血栓形成的功效。在本提案中，我们将进一步优化三个候选机顶盒 制剂（目标1），在体外和离体动脉模型中测试它们（目标2），并最终评估 STB在抗凝猪栓塞模型中的性能（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).