Association between Serum Calcium Level and Hemorrhagic Progression in Patients with Traumatic Intraparenchymal Hemorrhage: Investigating the Mediation and Interaction Effects of Coagulopathy

In this study, we investigate the association of serum calcium with coagulopathy and hemorrhagic progression contusion (HPC) in patients with traumatic intraparenchymal hemorrhage (tIPH), and further explore the interaction and mediation effect between serum calcium and coagulopathy on HPC. We conducted retrospective analyses of patients with tIPH admitted to the First Affiliated Hospital of Wenzhou Medical University between January 2016 to December 2019. The clinical data, coagulation parameters, and serum calcium levels were collected for further analysis. Multi-variate logistic regression analysis was applied to identify the association of serum calcium level with coagulopathy and HPC. Causal mediation analysis (CMA) and additive interaction model were used to estimate the interaction and mediation effect between serum calcium as well as coagulopathy on HPC. Additionally, we repeated the analysis using corrected calcium. A total of 473 patients were included in this study. Of these, 54 (11.4%) patients had hypocalcemia at admission, 105 (22.2%) presented with coagulopathy, and 187 (39.5%) experienced HPC. Admission serum calcium level in patients presented with coagulopathy and HPC were 8.84 (interquartile range [IQR]: 8.44-9.40] and 8.92 (IQR: 8.48-9.40) mg/dL respectively, which were significantly lower than that of patients without coagulopathy (9.10 [IQR: 8.68-9.88] and 9.12 [IQR: 8.72-9.89] mg/dL; all p < 0.001). Multi-variate logistic regression analysis identified that hypocalcemia emerged as an independent risk factor for coagulopathy and HPC. However, no significant interaction was detected between hypocalcemia and coagulopathy. CMA showed that the mediator coagulopathy explained 24.4% (95% confidence interval: 4.7-65.0%; p = 0.006) of the association between hypocalcemia and HPC. Moreover, comparable results were held using corrected calcium, as well. Admission serum calcium level is associated with the HPC for patients with tIPH and this relationship is partially mediated by coagulopathy, but no significant interaction is detected. Further studies are needed to validate the findings and explore its mechanisms.