The timely diagnosis and optimal management of hemostatic dysfunction in trauma and surgical patients is challenging due to the unavailability of suitable analytical tools. The current need to conduct multiple tests with multiple blood samples on multiple devices to ascertain the specific nature of the hemostatic defect by examining the different platelet aggregation and coagulation pathways is time consuming and cumbersome. Constrained by the time-critical nature of treating a bleeding patient, clinicians are often forced to use unguided, generic transfusion algorithms that may be sub-optimal for some patients. An on-site hemostasis analyzer that rapidly provides a broadly instructive report on multiple platelet and coagulation functions on a unified platform from a single blood sample on a single cartridge tested on a single device at the point-of-care has the potential to shift the guided blood product transfusion paradigm. To address this compelling need, the applicants have developed a hemostasis analyzer with a multichamber cartridge that can simultaneously assess multiple platelet aggregation and coagulation pathways from a single blood sample in less than 5 minutes. This cartridge interfaces with a base unit containing optoelectronic modules to detect and quantify platelet aggregation and clotting times in whole blood. The data from the instrument can be integrated into the patient's electronic health record that can be accessed by different clinicians to track the patient's hemostatic recovery trend. The goal of the proposed feasibility studies is to demonstrate that the novel hemostasis analyzer can reliably and reproducibly assess the status of platelet and coagulation functions in normal and hemostatically deficient blood. Platelet aggregation induced by adenosine di-phosphate (ADP), Collagen, and Arachidonic acid, and coagulation assessed by prothrombin time, activated partial thromboplastin time, and thrombin time will be measured in a 6-chamber cartridge. Sensitivity of the analyzer to coagulopathy will be tested by using clotting factor deficient blood in vitro and by testing blood from patients taking warfarin. Sensitivity of the analyzer to platele dysfunction will be tested by using blood from patients taking aspirin and ADP-receptor blockers (e.g. clopidogrel). Platelet function and clotting times of blood from trauma patients before and after restoration of hemostatic function will also be tested. For comparison, platelet aggregation and clotting times will be tested using conventional clotting time analyzers and platelet aggregometers. The expected outcome of this proof-of-concept phase of the project is the demonstration that multifactorial hemostatic function and deficiencies in specific hemostasis pathways can be rapidly assessed in the novel single platform system, paving the way for commercial development of a hemostasis analyzer that will facilitate guided transfusion of blood products to trauma and surgical patients.
Public Health Relevance Statement: Public Health Relevance: Blood clotting and bleeding problems are significant healthcare challenges. The diagnosis and management of such problems is particularly difficult in surgical and traumatic injury patients. Testing the function of platelets, a blood cell that plas an important role in blood clotting, and coagulation (mediated by proteins in the blood) in such patients is required to optimize transfusion of blood products such as plasma and platelet packs. However, current tests are cumbersome and time-consuming to perform. This project aims to demonstrate the feasibility of a novel system to test a broad range of platelet and coagulation functions rapidly at the point of care with a single sample of blood tested on a single cartridge. f this feasibility study is successful, a new technology will be developed to significantly facilitat the diagnosis and management of bleeding and blood clotting problems in a wide range of patients, including surgical and trauma patients.
NIH Spending Category: Bioengineering; Clinical Research; Hematology
Project Terms: Activated Partial Thromboplastin Time measurement; Address; Adenosine; Adult; Agonist; Agreement; Algorithms; analytical tool; Arachidonic Acids; Aspirin; base; Blood; Blood Cells; Blood coagulation; Blood Coagulation Disorders; Blood Coagulation Factor; Blood Platelets; blood product; Blood specimen; Blood Tests; clopidogrel; Coagulation Process; Collagen; Data; Defect; design; Detection; Development; Devices; Diagnosis; Electronic Health Record; Electronics; Feasibility Studies; Foundations; Functional disorder; Generic Drugs; Goals; Healthcare; Hemorrhage; Hemostatic Agents; Hemostatic function; In Vitro; in vitro testing; Individual; Injury; innovation; inorganic phosphate; instrument; Investigation; Measurable; Measurement; Measures; Mediating; Microfluidics; Movement; Nature; new technology; novel; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Phase; phase 1 study; Plasma; Platelet aggregation; Platelet Function Tests; point of care; product development; Prostaglandin-Endoperoxide Synthase; Proteins; Prothrombin time assay; Protocols documentation; public health relevance; Reaction; receptor; Recovery; Reporting; restoration; Role; Sampling; Site; System; Testing; Thrombin Time Assay; Time; Transfusion; Trauma; Trauma patient; trend; volunteer; Warfarin; Whole Blood
