Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, FL, USA.
Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
NPJ Syst Biol Appl. 2021 Dec 7;7(1):44. doi: 10.1038/s41540-021-00202-9.
Current trauma-induced coagulopathy resuscitation protocols use slow laboratory measurements, rules-of-thumb, and clinician gestalt to administer large volumes of uncharacterized, non-tailored blood products. These one-size-fits-all treatment approaches have high mortality. Here, we provide significant evidence that trauma patient survival 24 h after hospital admission occurs if and only if blood protein coagulation factor concentrations equilibrate at a normal value, either from inadvertent plasma-based modulation or from innate compensation. This result motivates quantitatively guiding trauma patient coagulation factor levels while accounting for protein interactions. Toward such treatment, we develop a Goal-oriented Coagulation Management (GCM) algorithm, a personalized and automated ordered sequence of operations to compute and specify coagulation factor concentrations that rectify clotting. This novel GCM algorithm also integrates new control-oriented advancements that we make in this work: an improvement of a prior thrombin dynamics model that captures the coagulation process to control, a use of rapidly-measurable concentrations to help predict patient state, and an accounting of patient-specific effects and limitations when adding coagulation factors to remedy coagulopathy. Validation of the GCM algorithm's guidance shows superior performance over clinical practice in attaining normal coagulation factor concentrations and normal clotting profiles simultaneously.
目前的创伤性凝血病复苏方案使用缓慢的实验室测量、经验法则和临床医生的整体判断来输注大量未经特征分析、非定制的血液制品。这些一刀切的治疗方法死亡率很高。在这里，我们提供了重要的证据，如果和仅如果血液蛋白凝血因子浓度平衡在正常值，无论是由于偶然的基于血浆的调节还是由于内在的补偿，创伤患者在入院后 24 小时的存活。这一结果促使我们定量指导创伤患者的凝血因子水平，同时考虑蛋白质相互作用。为了实现这种治疗，我们开发了一种目标导向的凝血管理（GCM）算法，这是一种个性化和自动化的操作顺序，用于计算和指定纠正凝血的凝血因子浓度。这种新颖的 GCM 算法还集成了我们在这项工作中取得的新的面向控制的进展：改进了之前的凝血酶动力学模型，该模型可以控制凝血过程，使用可快速测量的浓度来帮助预测患者状态，并在添加凝血因子以纠正凝血病时考虑患者特异性影响和限制。GCM 算法的指导验证表明，在同时达到正常凝血因子浓度和正常凝血谱方面，其性能优于临床实践。
