1. Associations of longitudinal D-Dimer and Factor II on early trauma survival risk
- Author
-
Richard M. Jiang, Arya A. Pourzanjani, Linda R. Petzold, and Mitchell J. Cohen
- Subjects
Male ,Disease ,030204 cardiovascular system & hematology ,Biochemistry ,Mathematical Sciences ,Factor II ,D-Dimer ,0302 clinical medicine ,Structural Biology ,80 and over ,Risk of mortality ,Clinical panel data ,Early trauma survival risk ,lcsh:QH301-705.5 ,Aged, 80 and over ,Applied Mathematics ,Biological Sciences ,Middle Aged ,Hyperfibrinolysis ,Computer Science Applications ,lcsh:R858-859.7 ,Longitudinal models ,Female ,Prothrombin ,Research Article ,Adult ,medicine.medical_specialty ,Adolescent ,Bioinformatics ,lcsh:Computer applications to medicine. Medical informatics ,Affect (psychology) ,Odds ,Fibrin Fibrinogen Degradation Products ,Joint models ,Young Adult ,03 medical and health sciences ,Clinical Research ,Information and Computing Sciences ,Consumptive Coagulopathy ,medicine ,Coagulopathy ,Humans ,Molecular Biology ,Survival analysis ,Aged ,Retrospective Studies ,business.industry ,Bayes Theorem ,030208 emergency & critical care medicine ,medicine.disease ,Survival Analysis ,Good Health and Well Being ,lcsh:Biology (General) ,Emergency medicine ,Wounds and Injuries ,business - Abstract
Background Trauma-induced coagulopathy (TIC) is a disorder that occurs in one-third of severely injured trauma patients, manifesting as increased bleeding and a 4X risk of mortality. Understanding the mechanisms driving TIC, clinical risk factors are essential to mitigating this coagulopathic bleeding and is therefore essential for saving lives. In this retrospective, single hospital study of 891 trauma patients, we investigate and quantify how two prominently described phenotypes of TIC, consumptive coagulopathy and hyperfibrinolysis, affect survival odds in the first 25 h, when deaths from TIC are most prevalent. Methods We employ a joint survival model to estimate the longitudinal trajectories of the protein Factor II (% activity) and the log of the protein fragment D-Dimer ($$\upmu$$ μ g/ml), representative biomarkers of consumptive coagulopathy and hyperfibrinolysis respectively, and tie them together with patient outcomes. Joint models have recently gained popularity in medical studies due to the necessity to simultaneously track continuously measured biomarkers as a disease evolves, as well as to associate them with patient outcomes. In this work, we estimate and analyze our joint model using Bayesian methods to obtain uncertainties and distributions over associations and trajectories. Results We find that a unit increase in log D-Dimer increases the risk of mortality by 2.22 [1.57, 3.28] fold while a unit increase in Factor II only marginally decreases the risk of mortality by 0.94 [0.91,0.96] fold. This suggests that, while managing consumptive coagulopathy and hyperfibrinolysis both seem to affect survival odds, the effect of hyperfibrinolysis is much greater and more sensitive. Furthermore, we find that the longitudinal trajectories, controlling for many fixed covariates, trend differently for different patients. Thus, a more personalized approach is necessary when considering treatment and risk prediction under these phenotypes. Conclusion This study reinforces the finding that hyperfibrinolysis is linked with poor patient outcomes regardless of factor consumption levels. Furthermore, it quantifies the degree to which measured D-Dimer levels correlate with increased risk. The single hospital, retrospective nature can be understood to specify the results to this particular hospital’s patients and protocol in treating trauma patients. Expanding to a multi-hospital setting would result in better estimates about the underlying nature of consumptive coagulopathy and hyperfibrinolysis with survival, regardless of protocol. Individual trajectories obtained with these estimates can be used to provide personalized dynamic risk prediction when making decisions regarding management of blood factors.
- Published
- 2021
- Full Text
- View/download PDF