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.
Public Health Relevance Statement: Project Narrative The clinical evaluation and management of hemostasis in the 5 millions 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.
Project Terms: Cytolysis; Lysis; Disease; disease/disorder; Disorder; Coagulation Process; Coagulation; Clotting; Dose; Defect; Equilibrium; balance function; balance; Blinded; Data; International; Reproducibility; research clinical testing; clinical test; Clinical Testing; Clinical Evaluation; Enrollment; enroll; Perioperative; Seminal; Small Business Innovation Research Grant; Small Business Innovation Research; SBIRS (R43/44); SBIR; Process; Development; developmental; Allergic Reaction; Fibrin; Fibrinogen; Factor One; Factor I; Coagulation Factor One; Coagulation Factor I; Blood Factor One; Blood Coagulation Factor One; Blood Coagulation Factor I; Fibrinolysis; Fibrinolyses; Cirrhosis; Fresh Frozen Plasmas; Affect; Patient Care; Patient Care Delivery; base; Blood specimen; Blood Sample; Goals; improved; Procedures; Hematocrit procedure; Packed Red-Cell Volume; Packed Erythrocyte Volume; Hematocrit; Hct; Hemolysis; Hemorrhage; blood loss; Bleeding; Hemostatic function; Hemostasis; Hemostatic Agents; Hemostatics; liver biopsy; Prophylactic treatment; Prophylaxis; Prevention Measures; Hospitals; Transfusion; TRNSF; Housing; Chronic; Clinical; Phase; Variant; Variation; In Vitro; Infection; Inpatients; Intensive Care Units; Training; Laboratories; Lead; heavy metal lead; heavy metal Pb; Pb element; Renal function; kidney function; Lipids; Liver; hepatic organ system; hepatic body system; Liver diseases; liver disorder; hepatopathy; Hepatic Disorder; liver transplantation; Liver Transplant; Liver Grafting; Hepatic Transplantation; Measurement; Morbidity - disease rate; Morbidity; Mortality Vital Statistics; Mortality; Functional disorder; pathophysiology; Physiopathology; Dysfunction; Patients; Physicians; Plasma; Reticuloendothelial System, Serum, Plasma; Plasma Serum; Blood Plasma; Alteplase; t-PA; Tissue-Type Plasminogen Activator; Tissue Plasminogen Activator; Tissue Activator D-44; T-Plasminogen Activator; Recombinant Tissue Plasminogen Activator; Platelet Count measurement; Platelet Number; Platelet Count; Blood Platelet Number; Blood Platelet Count; tool; Proteins; gene product; instrument; Diagnostic; Research; Resources; Research Resources; Risk; medical schools; school of medicine; medical college; Whole Blood; Solutions; Mechanics; mechanical; Technology; Testing; Thrombocytopenia; Thrombopenia; Time; Transplantation; transplant; Ultrasonography; ultrasound scanning; ultrasound imaging; ultrasound; sound measurement; sonography; sonogram; diagnostic ultrasound; Ultrasound Test; Ultrasound Medical Imaging; Ultrasound Diagnosis; Ultrasonogram; Ultrasonic Imaging; Medical Ultrasound; Echotomography; Echography; Universities; Virginia; Investigation; Work; Clinic; Source; blood product; Bacterial Infections; bacterial disease; Viral; Outcome Study; Bilirubin; Bilirubin IX alpha; Biomedical Engineering; bioengineering; Services; Adverse reactions; Accident and Emergency department; Emergency room; Emergency Department; Blood Banks; Blood coagulation; Blood Clotting; Blood Coagulation Factor; clotting factor; Coagulation Factors; Blood Platelets; thrombocyte/platelet; Thrombocytes; Platelets Reticuloendothelial System; Platelets; Marrow platelet; Hayem's elementary corpuscle; Deetjeen's body; Bizzozero's corpuscle/cell; Transplant Surgeon; experience; Performance; novel; research study; experimental study; experimental research; experiment; Human Resources; personnel; Manpower; Reporting; Generations; Measures; Admission activity; Admission; Cost Savings; Liver Failure; Hepatic Failure; symposium; conference; Diagnostic tests; Healthcare; health care; Hepatology; Normal Range; Normal Values; Sampling; response; Intervention; interventional strategy; Intervention Strategies; Clinical Research; Clinical Study; cost; time use; design; designing; clinical efficacy; Outcome; prospective; Evidence based intervention; graphical user interface; graphic user interface; Graphical interface; novel diagnostics; next generation diagnostics; new diagnostics; healthy volunteer; prototype; high risk; public health relevance; patient population; standard of care; clinical practice; adverse outcome; adverse consequence
