Integrated Coagulation Sensing to Predict Hemorrhage and Guide Transfusions

摘要 本项目的目标是开发一种综合凝血仪器方法，用于 在心脏手术后预测出血事件和定制血液成分输血的护理点。 超过50%的患者发生严重出血，通常是凝血功能受损或凝血障碍所致 复杂的心脏手术后多种因素，包括凝血因子耗竭，血小板受损 纤维蛋白溶解途径的功能和系统性激活有助于凝血病的发展。到 管理凝血缺陷，输注血液成分以纠正出血异常。不足 或延迟输血可导致危及生命的失血和器官衰竭，而过度使用同种异体 血液可能导致急性肺损伤、肾衰竭和心脏手术后死亡率增加。为了 实现最佳结果并挽救生命，临床工具可以快速预测心脏术后大出血 手术是必不可少。不幸的是，在快速变化的背景下，实验室测试是无效的。 危重心脏病患者的凝血状况，导致输血触发通常不精确， 不充分，在许多情况下，临床上不必要。这些因素加在一起， 对患者来说，浪费稀缺资源导致血液供应不足， 为有需要的患者提供产品。这种可怕的情况促使一个I类建议， 胸外科医师协会通过即时凝血试验定制输血决策， 并辅以综合输血算法。我们的提案直接针对这项建议。 在这里，我们提出了一种新的方法，称为iCoagLab，测量多个凝血参数， 在床边不到10分钟即可识别心脏手术后出血风险较高的患者， 定制输血要求并在治疗期间监测止血。这项技术涉及到放置一些 在一个小盒子里的几滴全血。激光光源照亮血液样本， 随时间从样品反射的激光散斑图案。通过分析激光散斑强度波动 在凝血过程中，我们可以同时量化多个凝血指标，包括凝血酶原时间， 活化凝血时间、凝血酶生成速率、纤维蛋白聚合、纤维蛋白溶解和血小板功能。的 光学设备将由一种算法补充，该算法将来自多路凝固的信息组合在一起 参数来预测出血严重程度并确定针对个体患者的输血策略。在 在我们工作的最后阶段，我们将进行研究，以评估新iCoagLab的准确性和实用性 一种预测心脏ICU患者出血风险和输血需求的方法， 手术

ABSTRACT The goal of this project is to develop an integrated coagulation instrument approach for use at the point-of-care to predict bleeding events and tailor blood component transfusion after cardiac surgery. Severe bleeding, frequently a result of impaired coagulation or coagulopathy, occurs in over 50% of patients after complex cardiac surgeries. Multiple factors including the depletion of clotting factors, impaired platelet function and the systemic activation of fibrinolytic pathways contribute to the development of coagulopathy. To manage defective coagulation, blood components are transfused to correct bleeding abnormalities. Inadequate or delayed transfusion can lead to life-threatening blood loss and organ failure, while overuse of allogenic blood may cause acute lung injury, renal failure and increased mortality after cardiac surgery. In order to achieve optimal outcome and save lives, clinical tools that can rapidly predict major bleeding following cardiac surgery are essential. Unfortunately, laboratory tests are ineffective in the context of rapidly changing coagulation conditions in critically-ill cardiac patients, resulting in transfusion triggers that are often imprecise, inadequate and in many cases, clinically unnecessary. Together, these factors pose detrimental complications for patients, and place a large burden on healthcare costs by wasting a scarce resource leading to blood product shortage for patients in need. This dire situation has prompted a Class I recommendation by the Society of Thoracic Surgeons for tailoring transfusion decisions via point-of-care coagulation tests that are supplemented with integrated transfusion algorithms. Our proposal directly addresses this recommendation. Here, we propose a novel approach termed iCoagLab that measures multiple coagulation parameters within less than 10 minutes at the bedside to identify patients at an elevated risk of bleeding after cardiac surgery, tailor transfusion requirements and monitor hemostasis during treatment. The technique involves placing a few drops of whole blood in a small cartridge. A laser source illuminates the blood sample and a camera images laser speckle patterns reflected from the sample over time. By analyzing laser speckle intensity fluctuations during coagulation, we can simultaneously quantify multiple coagulation metrics including prothrombin time, activated clotting time, thrombin generation rate, fibrin polymerization, fibrinolysis, and platelet function. The optical device will be supplemented by an algorithm that combines information from multiplexed coagulation parameters to predict bleeding severity and identify transfusion strategies tailored to the individual patient. In the final phase of our work, we will conduct studies to evaluate the accuracy and utility of the new iCoagLab approach to predict bleeding risk and transfusion requirements in patients admitted to the cardiac ICU following surgery.