A diagnostic instrument to manage hemostasis in chronic liver disease

一种用于治疗慢性肝病止血的诊断仪器

• 批准号: 8324671
• 负责人: FRANCESCO VIOLA
• 金额: $ 63.19万
• 依托单位: HEMOSONICS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8324671
• 关键词: Accident and Emergency department; Admission activity; Adverse reactions; Affect; Allergic Reaction; Alteplase; Bacterial Infections; Bilirubin; Biomedical Engineering; Blinded; Blood Banks; Blood Coagulation Factor; Blood Platelets; Blood coagulation; Blood specimen; Cirrhosis; Clinic; Clinical; Clinical Management; Clinical Research; Coagulation Process; Cost Savings; Cytolysis; Data; Defect; Diagnostic; Diagnostic tests; Disease; Dose; Enrollment; Equilibrium; Evidence based intervention; Fibrin; Fibrinogen; Fibrinolysis; Fresh Frozen Plasmas; Functional disorder; Generations; Goals; Healthcare; Hematocrit procedure; Hemolysis; Hemorrhage; Hemostatic Agents; Hemostatic function; Hepatology; Hospitals; Housing; Human Resources; In Vitro; Infection; Inpatients; Intensive Care Units; International; Intervention; Investigation; Laboratories; Lead; Lipids; Liver Failure; Liver diseases; Measurement; Measures; Mechanics; Morbidity - disease rate; Normal Range; Outcome; Outcome Study; Patient Care; Patients; Performance; Perioperative; Phase; Physicians; Plasma; Platelet Count measurement; Procedures; Process; Prophylactic treatment; Proteins; Renal function; Reporting; Reproducibility; Research; Resources; Risk; Sampling; Seminal; Services; Small Business Innovation Research Grant; Solutions; Source; Technology; Testing; Thrombocytopenia; Time; Training; Transfusion; Transplant Surgeon; Transplantation; Ultrasonography; Universities; Variant; Virginia; Virus Diseases; Whole Blood; Work; adverse outcome; base; blood product; chronic liver disease; clinical efficacy; clinical practice; cost; design; experience; graphical user interface; healthy volunteer; high risk; improved; instrument; liver biopsy; liver transplantation; medical schools; mortality; novel; novel diagnostics; patient population; prospective; prototype; public health relevance; research clinical testing; research study; response; standard of care; symposium; time use; tool

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.

描述（由申请人提供）：在500万慢性肝病（CLD）患者中，对止血的临床评价和管理知之甚少。在两个国际肝病凝血研讨会上提出的数据和最近一期肝病临床总结的数据强烈支持该领域存在未满足的临床研究需求。需要改进止血调查，以评估出血风险并指导临床决策。下表中列出了一些例子，展示了如何改善CLD患者的临床实践。如肝活检等侵入性干预的临床决定改善止血评估=>如果止血情况显示出血风险高，不要进行手术使用血液制品用于预防或治疗目的改善止血评估=>指导血液制品的选择和输血：(i)新鲜冷冻血浆（FFP）和/或冷冻沉淀以补充凝血蛋白。（ii）浓缩血小板以补充血小板水平。（iii）抗纤溶药物以减缓血块溶解。血液制品输注的围手术期管理（如肝移植）改进的止血评估=>以上输血指南急诊室和重症监护病房的临床决策改进的止血评估=>以上输血指南对于有出血风险或经历出血发作的CLD患者，血液制品的管理尤为重要。然而，应谨慎优化血液制品的使用，以节省稀缺资源，尽量减少过敏反应、病毒和细菌感染的风险，并减少卫生保健支出。最近的一份报告表明，仅改善肝移植中的止血管理每年就可以节省37万美元以上（假设一家医院每年进行42例移植手术），同时将血制品过度输血相关的并发症减少2.6倍。不幸的是，目前还没有一种可行的综合性止血测试方法，能够为CLD患者提供准确的治疗。虽然一些研究表明，目前的测试不能有效地量化CLD的止血功能，也与出血结果无关，但每天都在使用这些毫无根据的标准做出临床决定，导致错误和潜在危险的治疗。自从开创性的研究表明目前的CLD测试是错误的以来，对替代方案的需求就很明显了。HemoSonics提出的解决方案：HemoSonics LLC正在开发一种仪器，HemoSonics全球止血分析仪或HS-GHA，可以量化止血功能，以指导适当的基于证据的干预措施。HS-GHA基于超声流变法（SR），这是一种基于超声的新型技术，不仅能够评估凝块时间（取决于血浆凝血因子），还能够评估凝块形成率（也取决于凝血因子）、凝块硬度（取决于纤维蛋白组装和血小板功能）和溶解时间（取决于纤维蛋白溶解蛋白）。如果证明是成功的，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节省成本；（iii）血库保存血液制品，最重要的是，（iv）改善病人的护理。拟议的SBIR工作：在第一阶段，我们打算完成证明SR作为一种诊断工具的可行性，以量化CLD中常见的止血异常。在这个II期，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独立的临床原型与一次性墨盒，并执行一个小的临床研究肝硬化患者。本研究的积极结论将证明超声测量识别导致过度出血和需要输注血液制品的特定止血缺陷的能力。这项研究是HemoSonics有限责任公司与弗吉尼亚大学生物医学工程系和医学院的合作成果。