A Near-Patient, Low Blood Volume Platform for Rapid Comprehensive Evaluation of Coagulation in Trauma Patients

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ABSTRACT A Near-Patient, Low Blood Volume Platform for Rapid Comprehensive Evaluation of Coagulation in Trauma Patients (Fast-Track SBIR) Trauma is a leading cause of death worldwide, with hemorrhage constituting the most common cause of preventable death after injury. A third of trauma patients develop coagulopathy, characterized by abnormal coagulation and inflammation, and require urgent transfusion to decrease the likelihood of organ failure and mortality. Patients with post-traumatic coagulopathy experience many changes facilitated by the endothelium, platelets, circulating coagulation factors, and immune system function, which make it difficult to assess using a single biomarker. Conventional coagulation tests are informative, but most are not adequate for acute hemorrhage control due to long result turnaround times (> 45 minutes). Viscoelastic coagulation tests, alternatively, can rapidly detect the presence of abnormal clotting, but necessitate longer test times (30-45 minutes) to provide results that may be used to determine specific changes in treatment. Repeated monitoring of hemostasis is recommended for bleeding trauma patients, however, the cumulative blood loss required for central laboratory coagulation tests (1-2 mL per test) increases the risk of iatrogenic anemia. The optimal coagulation panel for rapid, recurrent assessment of coagulation in trauma patients does not yet exist. To address the critical unmet need for rapid, low volume tests for the diagnosis and therapeutic management of coagulopathy in trauma patients, we will develop a four-assay panel and corresponding near-patient digital microfluidic (DMF) platform that will provide clinically actionable data to guide the administration of whole blood transfusion and other blood products. Our innovative technology will simultaneously measure prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), fibrinogen, and platelet count from < 50 µL of whole blood. All assay operations, including plasma separation from whole blood, will be performed autonomously, facilitating use by minimally trained users in near-patient settings such as the emergency department and operating room. By combining four essential assays in a single protocol with a time- to-result of under 10 minutes, our system will better inform transfusion requirements, reduce iatrogenic blood loss from recurrent coagulation monitoring, and improve clinical workflow in busy trauma settings. Phase I of this Fast-Track SBIR project will establish feasibility of the testing panel by developing a DMF instrument capable of simultaneously measuring PT/INR, aPTT, and fibrinogen on a single disposable cartridge. We will also validate DMF-compatible hardware for the optical system required for platelet count measurement. Phase II will integrate the optical system and complementary cartridge into our existing DMF platform to support full automation of the platelet count assay. We will then multiplex the assays in a single run and evaluate the analytical and clinical performance of each test. Our final product will be marketed for use in general and military trauma settings during triage and perioperative periods, with secondary markets including adult and pediatric patients undergoing surgery or other procedures that raise the risk for hemorrhage and shock.