International Journal of Molecular Medical Science, 2025, Vol.15, No.2, 54-68 http://medscipublisher.com/index.php/ijmms 65 protein C), and the decrease in procoagulant factors is related to the degree of prematurity. An excessive decrease in procoagulant factors can promote the occurrence of VTE (Fort et al., 2022). The high incidence of VTE in adolescents is attributed to their thin vascular walls, high blood viscosity, and high activity levels. In terms of diseases, inflammatory bowel disease and trauma are the main VTE risk factors; in daily habits, obesity and prolonged sitting are key factors. Inflammatory bowel disease damages the intestinal mucosa, causing ulceration, platelet aggregation, and coagulation system activation. Traumatized patients also need platelet aggregation and coagulation system activation for tissue repair. Adolescents' high blood viscosity further elevates the VTE risk. Obese children's blood clots more easily than that of normal children. Besides, adolescents' long-term sitting for study, video-watching, or gaming leads to venous stasis and VTE. Poor daily habits not only trigger VTE but also promote its recurrence in children (Biss et al., 2016; Srivaths and Dietrich, 2016). Thus, healthcare providers should monitor adolescents' disease status and lifestyle, enhance health education during treatment, assist them in correcting unhealthy habits, and reduce VTE incidence and recurrence. Model-building researchers can focus on childhood's high-risk periods, create targeted risk prediction models, and promote children's health. At present, the construction of risk prediction models for venous thromboembolism (VTE) in children faces a dynamic balance between the dominance of clinical variables and the application potential of biomarkers. Existing models are mostly based on clinical variables (such as central venous catheter, age, surgery, etc.), and the integration of VTE-related biomarkers is still in the exploratory stage. Studies have shown that D-dimer, as a fibrin degradation product, presents a specific increase in the occurrence of VTE in children, and its dynamic monitoring can reflect the real-time coagulation status. C-reactive protein (CRP) complements risk assessment in children with specific inflammation-related diseases by characterizing the association between inflammation and thrombosis. The inclusion of these biomarkers is expected to break the bottleneck of current model prediction efficiency, but at the same time, it also aggravates the challenges of model complexity and heterogeneity. Notably, when the model had more than 5 predictors, the meta-analysis showed a significant increase in heterogeneity. This phenomenon is due to the interweaving of multiple factors: first, the combination of biomarkers and clinical variables needs to account for physiological differences in the age stratification (newborn to adolescent), such as the normal range of D-dimer changes with age; Secondly, differences in global medical practice (such as the use of central venous catheters between East and West) lead to shifts in the weight of predictors. Furthermore, variable selection bias (such as focusing on disease factors or treatments) exacerbates incomparability between models. For example, simultaneous integration of D-dimer, CRP, and clinical variables requires both addressing the interaction effects of biomarkers and age and reconciliating geographic heterogeneity in the importance of variables in different healthcare Settings. In future studies, researchers need to adopt a dual strategy: at the longitudinal level, establish age-specific biomarker thresholds through multicenter cohorts, and analyze their nonlinear associations with clinical variables using machine learning; At the horizontal level, a core predictive factor subset (e.g., limited to 5 key variables) is used as a cross-regional baseline, while allowing region-specific expansion variables (e.g., strengthening infection-related indicators in Southeast Asia). This “core + extension” model architecture can not only maintain the homogeneity of meta-analysis, but also retain the advantage of biomarkers to improve prediction accuracy, and ultimately achieve the optimal balance between precision medicine and clinical universality of VTE risk assessment tools in children. In future clinical work, based on the results of this study, the following five clinical recommendations are put forward for medical staff: ①The use of central venous catheter (CVC) should be strictly controlled, the retention time should be reduced and monitoring should be done, especially in resource-limited areas, alternative risk factors should be paid attention to. ②For children of different ages, such as newborns, infants and adolescents, targeted management should be conducted according to their physiological characteristics and risk factors. ③The risk of VTE should be evaluated comprehensively in children with surgery and trauma, and preventive measures should be reasonably selected and blood transfusion management should be standardized. ④Dynamic monitoring
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