A diagnostic instrument to manage hemostasis in chronic liver disease

描述(由申请人提供)：对500万慢性肝病(CLD)患者止血的临床评估和处理尚不清楚。在两个关于肝病凝血的国际研讨会上提出的数据和在最近一期的《肝病临床》中总结的数据有力地支持了在这一领域的研究存在未得到满足的临床需求。需要改进止血研究，以评估出血风险并指导临床决策。下表列出了几个例子，说明如何改进CLD患者的临床实践。肝活检等侵入性干预措施的临床决策改善了止血评估=；如果止血档案显示出血风险很高，不要进行手术；将血液产品用于预防或治疗目的改善止血评估=指导血液产品的选择和输注：(I)新鲜冰冻血浆(FFP)和/或冷沉淀物以补充凝血蛋白。(Ii)浓缩血小板以补充血小板水平。(Iii)抗纤溶药物，以减缓血栓的溶解。对输血产品的围术期管理，例如在肝移植的情况下，改善了对止血产品的评估如上所述；指导输血产品的临床决定如上所述在急诊室和重症监护病房改进了对止血产品的评估如上所述对血液产品的管理对于有出血风险或经历出血发作的CLD患者尤其重要。然而，应该谨慎地优化血液产品的使用，以节省稀缺的资源，最大限度地减少过敏反应、病毒和细菌感染的风险，并减少医疗保健支出。最近的一份报告表明，仅改善肝移植止血管理一项就可以每年节省超过37万美元(假设一家医院每年进行42次移植)，同时将与过度输血产品相关的并发症减少2.6倍。不幸的是，没有可行的全面止血试验能够为CLD患者提供准确的治疗。虽然一些研究表明，目前的测试无法有效地量化CLD的止血功能，并且与出血结果没有相关性，但临床决策每天都使用这些毫无根据的标准，导致错误和潜在的危险治疗。自从开创性研究表明目前CLD测试的谬误以来，对替代品的需求一直是显而易见的。HemoSonics提出的解决方案：HemoSonics LLC正在开发一种仪器，HemoSonics的全球止血分析仪或HS-GHA，它可以量化止血功能，以指导适当的循证干预。HS-GHA基于超声流变仪(SR)，这是一项基于超声的新技术，不仅能够评估凝块形成时间(取决于血浆凝血因子)，还能够评估凝块形成率(还取决于凝血因子)、凝块硬度(取决于纤维蛋白组装和血小板功能)和溶解时间(取决于纤溶蛋白)。如果证明成功，HS-GHA将有助于：(I)医生提供正确的治疗；(Ii)医院通过减少不必要的输血来节省成本；(Iii)血库保存血液产品；以及最重要的是，(Iv)改善患者的护理。建议的SBIR工作：在第一阶段，我们打算完成SR作为量化CLD中常见的止血异常的诊断工具的可行性的论证。在这个第二阶段，我们打算展示我们的技术的临床价值和商业潜力。我们将设计和组装一个带有一次性药盒的独立临床原型，并对肝硬变患者进行一项小型临床研究。这项研究的积极结论将证明超声流变仪能够识别导致出血过多和需要输血产品的特定止血缺陷。这项研究是HemoSonics，LLC和弗吉尼亚大学生物医学工程系和医学院的合作成果。 公共卫生相关性：对500万慢性肝病(CLD)患者止血的临床评估和处理方法知之甚少。虽然改进的止血管理可以解决改善患者护理和节省大量成本的问题，但由于现有诊断测试的许多限制，这项任务目前仍然不是最理想的。这项SBIR建议的目标是开发和测试一种新型诊断仪器的临床疗效，该仪器将改善CLD患者目前的止血管理，从而改善患者的预后并产生显著的成本节约。

DESCRIPTION (provided by applicant): The clinical evaluation and management of hemostasis in the 5 million patients affected by chronic liver diseases (CLD) is poorly understood. Data presented at two International Symposia on Coagulation in Liver Disease and summarized in a recent edition of Clinics in Liver Disease strongly support the presence of an unmet clinical need for investigation in this field. Improved investigation of hemostasis is needed to assess bleeding risks and guide clinical decisions. Few examples are listed in the table below, showing how clinical practice could be improved for CLD patients. Clinical decision for invasive interventions such as liver biopsy Improved assessment of hemostasis => Don't perform procedure if hemostatic profile reveals high risk of bleeding Usage of blood products for prophylaxis or therapy purposes Improved assessment of hemostasis => Guide the selection and transfusion of blood products: (i) Fresh frozen plasma (FFP) and/or cryoprecipitate to replenish blood coagulation proteins. (ii) Platelet concentrates to replenish platelets level. (iii) Anti-fibrinolytics to slow down clot dissolution. Perioperative management of blood product transfusions such as in the case of liver transplant Improved assessment of hemostasis => Guide transfusion of blood products as above Clinical decisions in the emergency room and intensive care unit Improved assessment of hemostasis => Guide transfusion of blood products as above The management of blood products is particularly important for in CLD patients at risk or experiencing bleeding episodes. However, the use of blood products should be carefully optimized in order to save scarce resources, minimize the risks of allergic reactions, viral and bacterial infections, and reduce health-care spending. A recent report indicated that improved management of hemostasis in liver transplant alone could save over $370K/year (assuming an hospital performing 42 transplants/year) while reducing complications related to over transfusion of blood products by 2.6X. Unfortunately, there is no viable comprehensive test of hemostasis able to provide accurate management of CLD patients. While several studies have shown that current tests are unable to effectively quantify the hemostatic functions in CLD and do not correlate with bleeding outcomes, clinical decisions are being made daily using these unfounded criteria, leading to erroneous and potentially hazardous treatments. The need for alternatives has been apparent since seminal studies showing the fallacy of current tests in CLD. HemoSonics' Proposed Solution: HemoSonics LLC is developing an instrument, the HemoSonics' Global Hemostasis Analyzer or HS-GHA that can quantify hemostasis function to guide appropriate and evidence based interventions. The HS-GHA is based on sonorheometry (SR), a novel ultrasound-based technology able to assess not only time to clot (dependent upon the plasma coagulation factors) but also clot formation rate (also dependent upon coagulation factors), clot stiffness (dependent upon fibrin assembly and platelet function), and time to lysis (dependent upon fibrinolytic proteins). If proven successful, the HS-GHA will help: (i) physicians provide the correct treatment, (ii) the hospital save costs by reducing unnecessary transfusions, (iii) the blood bank save blood products, and, most importantly, (iv) improve patient's care. Proposed SBIR Work: In Phase I we intend to complete demonstration of the feasibility of SR as a diagnostic tool to quantify abnormalities of hemostasis that are common in CLD. In this Phase II we intend to demonstrate the clinical value and thus the commercial potential of our technology. We will design and assemble a stand- alone clinical prototype with disposable cartridges, and perform a small clinical study on cirrhotic patients. A positive conclusion from this study will demonstrate the ability of sonorheometry to recognize specific hemostatic defects that lead to excessive bleeding and the need to transfuse blood products. This research is a collaborative effort between HemoSonics, LLC and the University of Virginia Department of Biomedical Engineering and School of Medicine. PUBLIC HEALTH RELEVANCE: The clinical evaluation and management of hemostasis in the 5 million patients affected by chronic liver diseases (CLD) is poorly understood. While improved management of hemostasis can resolve in improved patients care and substantial cost savings, this task currently remains suboptimal due to the many limitations of available diagnostic tests. The goal of this SBIR proposal is to develop and test the clinical efficacy of a novel diagnostic instrument that will improve the current management of hemostasis in CLD patients, thus improving patients' outcomes and generating significant cost savings.