Machine learning model for predicting physical activity related bleeding risk in Chinese boys with haemophilia A

Di Ai; Chang Cui; Yongqiang Tang; Yan Wang; Ningning Zhang; Chenyang Zhang; Yingzi Zhen; Gang Li; Kun Huang; Guoqing Liu; Zhenping Chen; Wensheng Zhang; Runhui Wu

doi:10.1016/j.thromres.2023.10.012

Machine learning model for predicting physical activity related bleeding risk in Chinese boys with haemophilia A

Thromb Res. 2023 Dec:232:43-53. doi: 10.1016/j.thromres.2023.10.012. Epub 2023 Oct 21.

Authors

Di Ai¹, Chang Cui², Yongqiang Tang³, Yan Wang⁴, Ningning Zhang⁵, Chenyang Zhang⁶, Yingzi Zhen¹, Gang Li⁷, Kun Huang¹, Guoqing Liu¹, Zhenping Chen⁸, Wensheng Zhang⁹, Runhui Wu¹⁰

Affiliations

¹ Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China.
² State Key Laboratory of Multimodal Artificial Intelligence Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 100049, China.
³ State Key Laboratory of Multimodal Artificial Intelligence Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: yongqiang.tang@ia.ac.cn.
⁴ Department of Rehabilitation, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
⁵ Department of Radiology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
⁶ State Key Laboratory of Multimodal Artificial Intelligence Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
⁷ Hematologic Disease Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
⁸ Hematologic Disease Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. Electronic address: chenzhenping@outlook.com.
⁹ State Key Laboratory of Multimodal Artificial Intelligence Systems, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: zhangwenshengia@hotmail.com.
¹⁰ Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 100045, China. Electronic address: runhuiwu@hotmail.com.

PMID: 37931538
DOI: 10.1016/j.thromres.2023.10.012

Abstract

Background: Physical activity is a crucial part of an active lifestyle for haemophiliac children. However, the fear of bleeds has been identified as barriers to participating physical activity for haemophiliac children even with prophylaxis. Lack of evidence and metrics driven by data is key problem.

Objectives: We aim to develop machine learning models based on clinical data with multiple potential factors considered to predict risk of physical activity bleeding for haemophilia children with prophylaxis.

Methods: From this cohort study, we collected information on 98 haemophiliac children with adequate prophylaxis (trough FVIII:C level > 1 %). The involved potential predictor variables include demographic information, treatment information, physical activity, joint evaluation, and pharmacokinetic parameters, etc. We applied CoxPH, Random Survival Forests (RSF) and DeepSurv to construct prediction models for the risk of bleeding during physical activities. All three survival analysis models were internally and externally validated.

Results: A total of 98 patients were enrolled in this study. Their median age was 7.9 (5.5, 10.2) years. The CoxPH, RSF and DeepSurv models' discriminative and calibration abilities were all high, and the RSF model had the best performance (Internal validation: C-index, 0.7648 ± 0.0139; Brier Score, 0.1098 ± 0.0015; External validation: C-index, 0.7260 ± 0.0154; Brier Score, 0.0930 ± 0.0018). The prediction curves demonstrated that the developed RSF model can distinguish the risks well between bleeding and non-bleeding patients, as well as patients with different levels of physical activity. Meanwhile, the feature importance analysis confirmed that physical activity bleeding was deduced by comprehensive effects of various factors, and the importance of different factors on bleeding outcome is discrepant.

Conclusions: This study revealed from the mechanism that it is necessary to incorporate multiple factors to accurately predict physical activity related bleeding risk. In clinical practice, the designed machine learning models can provide guidance for children with haemophilia A to positively participate in physical activity.

Keywords: Bleeding predictive modelling; Children; Haemophilia; Machine learning; Physical activity.

MeSH terms

Child
Cohort Studies
East Asian People
Exercise
Hemophilia A* / complications
Hemophilia A* / drug therapy
Hemorrhage / etiology
Humans
Machine Learning
Male