CLINICAL AND PROCEDURAL PREDICTORS OF THROMBOSIS IN HOSPITALIZED CHILDREN
7 affiliations
- 1Centro de Hematologia e Hemoterapia (Hemocentro), Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
- 2Faculdade de Engenharia Química, Laboratório de Otimização, Projeto e Controle Avançado, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
- 3Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
- 4Centro Infantil Boldrini, Campinas, Brazil
- 5Departamento de Engenharia Química, Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo (UNIFESP), Diadema, Brazil
- 6Department of Medicine (DIMED), University of Padua, Italy
- 7The Hospital for Sick Children, University of Toronto, Canada
Abstract
Background: Venous thromboembolism (VTE), although uncommon in pediatric populations, occurs more frequently in hospitalized children. Robust, prospectively derived risk prediction models for symptomatic VTE remain limited in this setting. Aims: To identify independent risk factors for VTE and to develop a predictive model for symptomatic thrombosis in hospitalized pediatric patients. Methods: This prospective multicenter cohort study (September 2018–January 2022) evaluated 2,722 pediatric patients (birth–18 years) across 5,040 hospitalizations, identifying 39 imaging-confirmed symptomatic VTE cases (1.43%). A multivariable logistic regression model was built using forward selection to incorporate clinical and procedural predictors. Adjusted odds ratios (95% CI) and model discrimination (out-of-bag C-index) were validated using 50,000 BCa bootstrap resamples. Results: Among 5,040 pediatric hospitalizations, 39 patients developed VTE (0.77% incidence; median age 5.0 years, 45.9% female). Compared to non-VTE controls, patients with VTE had significantly higher rates of ICU admission (79.5% vs. 26.6%), central venous catheterization (69.2% vs. 29.8%), bed immobilization (76.9% vs. 37.4%), cardiovascular disease (17.9% vs. 3.0%), and neurological disease (12.8% vs. 3.2%; all p < 0.01). Furthermore, VTE was associated with a markedly prolonged median hospital stay (29.5 vs. 5.0 days, p < 0.001). Increasing age was associated with higher risk (aOR 1.07 per year; 95% CI, 1.03–1.12), as were intensive care unit admission (aOR 1.91; 95% CI, 1.42–2.66) and longer length of hospitalization (aOR 1.01 per day; 95% CI, 1.01–1.02). Procedural factors showed the strongest associations with thrombosis, including 2≥ catheter insertion attempts (aOR 6.47; 95% CI, 2.81–14.49), femoral venous catheter (aOR 28.22; 95% CI, 7.23–90.36), and cervicothoracic venous catheter (aOR 4.71; 95% CI, 2.84–7.94). The final model demonstrated strong discriminative performance, with a C-index of 0.90 (95% CI, 0.83–0.97), sensitivity of 0.85, specificity of 0.78, and a negative predictive value of 0.99. Risk factors for symptomatic pediatric thrombosis were evaluated using multivariable logistic regression (forward selection with 50,000 BCa bootstrap resamples) alongside ten machine learning (ML) algorithms (70/30 train–test split, 10-fold cross-validation, and SHAP explainability analysis). Both statistical modeling and ML approaches independently converged on the exact same clinical and procedural predictors, confirming the biological and clinical validity of the identified risk drivers. Discussion: Aligning with prior literature, the use of femoral access and insertion attempts are likely mediated by mechanical endothelial disruption, flow turbulence, catheter mechanical distress, and emergency access placement. Targeted protocols aiming to minimize catheter manipulation and avoid high-risk sites like the femoral vein are essential for VTE prevention. Conclusion: Symptomatic VTE in hospitalized children is strongly influenced by modifiable procedural and clinical factors. This predictive model shows high discriminative performance and may support individualized risk stratification and targeted thromboprophylaxis strategies in pediatric inpatient care – after external validation and clinical impact assessment. Approved by Ethics Committee of UNICAMP (CAAE: 87364418.2.1001.5404). Supported by FAPESP (#2016/14172-6).
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BibTeX
@article{huber2026clinical,
title = {{CLINICAL AND PROCEDURAL PREDICTORS OF THROMBOSIS IN HOSPITALIZED CHILDREN}},
author = {Stephany Cares HUBER and Mohamad Al BANNOUD and Silmara Aparecida de Lima MONTALVÃO and Sandra Martins SILVA and Sumara Zuanazi Pinto RIGATTO and Ricardo Onofre Benez VILELA and Arlindo Nascimento Lemos JUNIOR and Mônica Pinheiro de Almeida VERÍSSIMO and Tiago Dias MARTINS and Gabriel Yoshiaki OTTAIANO and Rubens Maciel FILHO and Walter AGENO and Leonardo Rodrigues BRANDÃO and Joyce Maria ANNICHINO-BIZZACCHI},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.108077},
url = {https://doi.org/10.1016/j.htct.2026.108077},
note = {CC BY},
}
RIS
TY - JOUR
TI - CLINICAL AND PROCEDURAL PREDICTORS OF THROMBOSIS IN HOSPITALIZED CHILDREN
AU - Stephany Cares HUBER
AU - Mohamad Al BANNOUD
AU - Silmara Aparecida de Lima MONTALVÃO
AU - Sandra Martins SILVA
AU - Sumara Zuanazi Pinto RIGATTO
AU - Ricardo Onofre Benez VILELA
AU - Arlindo Nascimento Lemos JUNIOR
AU - Mônica Pinheiro de Almeida VERÍSSIMO
AU - Tiago Dias MARTINS
AU - Gabriel Yoshiaki OTTAIANO
AU - Rubens Maciel FILHO
AU - Walter AGENO
AU - Leonardo Rodrigues BRANDÃO
AU - Joyce Maria ANNICHINO-BIZZACCHI
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.108077
UR - https://doi.org/10.1016/j.htct.2026.108077
AB - Background: Venous thromboembolism (VTE), although uncommon in pediatric populations, occurs more frequently in hospitalized children. Robust, prospectively derived risk prediction models for symptomatic VTE remain limited in this setting. Aims: To identify independent risk factors for VTE and to develop a predictive model for symptomatic thrombosis in hospitalized pediatric patients. Methods: This prospective multicenter cohort study (September 2018–January 2022) evaluated 2,722 pediatric patients (birth–18 years) across 5,040 hospitalizations, identifying 39 imaging-confirmed symptomatic VTE cases (1.43%). A multivariable logistic regression model was built using forward selection to incorporate clinical and procedural predictors. Adjusted odds ratios (95% CI) and model discrimination (out-of-bag C-index) were validated using 50,000 BCa bootstrap resamples. Results: Among 5,040 pediatric hospitalizations, 39 patients developed VTE (0.77% incidence; median age 5.0 years, 45.9% female). Compared to non-VTE controls, patients with VTE had significantly higher rates of ICU admission (79.5% vs. 26.6%), central venous catheterization (69.2% vs. 29.8%), bed immobilization (76.9% vs. 37.4%), cardiovascular disease (17.9% vs. 3.0%), and neurological disease (12.8% vs. 3.2%; all p < 0.01). Furthermore, VTE was associated with a markedly prolonged median hospital stay (29.5 vs. 5.0 days, p < 0.001). Increasing age was associated with higher risk (aOR 1.07 per year; 95% CI, 1.03–1.12), as were intensive care unit admission (aOR 1.91; 95% CI, 1.42–2.66) and longer length of hospitalization (aOR 1.01 per day; 95% CI, 1.01–1.02). Procedural factors showed the strongest associations with thrombosis, including 2≥ catheter insertion attempts (aOR 6.47; 95% CI, 2.81–14.49), femoral venous catheter (aOR 28.22; 95% CI, 7.23–90.36), and cervicothoracic venous catheter (aOR 4.71; 95% CI, 2.84–7.94). The final model demonstrated strong discriminative performance, with a C-index of 0.90 (95% CI, 0.83–0.97), sensitivity of 0.85, specificity of 0.78, and a negative predictive value of 0.99. Risk factors for symptomatic pediatric thrombosis were evaluated using multivariable logistic regression (forward selection with 50,000 BCa bootstrap resamples) alongside ten machine learning (ML) algorithms (70/30 train–test split, 10-fold cross-validation, and SHAP explainability analysis). Both statistical modeling and ML approaches independently converged on the exact same clinical and procedural predictors, confirming the biological and clinical validity of the identified risk drivers. Discussion: Aligning with prior literature, the use of femoral access and insertion attempts are likely mediated by mechanical endothelial disruption, flow turbulence, catheter mechanical distress, and emergency access placement. Targeted protocols aiming to minimize catheter manipulation and avoid high-risk sites like the femoral vein are essential for VTE prevention. Conclusion: Symptomatic VTE in hospitalized children is strongly influenced by modifiable procedural and clinical factors. This predictive model shows high discriminative performance and may support individualized risk stratification and targeted thromboprophylaxis strategies in pediatric inpatient care – after external validation and clinical impact assessment. Approved by Ethics Committee of UNICAMP (CAAE: 87364418.2.1001.5404). Supported by FAPESP (#2016/14172-6).
SN - 2531-1379
SN - 2531-1387
ER -