Ex Vivo Effect of Apixaban on Hemostatic Biomarkers in Children With Heart Disease: A SAXOPHONE Trial Substudy
Clinical Snapshot
PICO Framework
| P — Population | Children aged >1 year with heart disease requiring thromboprophylaxis (n=182) |
| I — Intervention | Apixaban (n=123) |
| C — Comparator | Standard of care (vitamin K antagonists or low-molecular-weight heparin) (n=59) |
| O — Outcomes | Hemostatic biomarkers including d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S at baseline, week 2, and month 6 |
Bottom Line
This biomarker substudy of the SAXOPHONE trial provides mechanistic insights into apixaban's anticoagulant effects in children with heart disease. The findings show that apixaban reduces hypercoagulability markers (decreased d-dimer) and appropriately prolongs coagulation parameters while preserving endogenous thrombin potential, similar to patterns seen in adults. However, as a substudy focusing on surrogate endpoints, it has inherent limitations including open-label design and lack of direct clinical outcome correlation. The biomarker changes support the biological plausibility of apixaban's efficacy demonstrated in the main SAXOPHONE trial. For Australian clinicians, these findings provide reassuring mechanistic data supporting apixaban as a viable alternative to traditional anticoagulants in paediatric heart disease patients, though clinical decision-making should primarily rely on the main trial's safety and efficacy outcomes rather than these surrogate biomarker changes.
Key Findings
P Value: Significance mentioned but specific p-values not provided
Effect Size: Decreased d-dimer levels at month 6 in all groups; prolonged thrombin generation lag time and time to peak with apixaban vs VKAs
Primary Outcome: Changes in hemostatic biomarkers at week 2 and month 6
Nnt Or Sensitivity: Not applicable for biomarker outcomes
Confidence Interval: Not reported in abstract
Clinical Application
Requires specialized coagulation laboratory capabilities for thrombin generation assays and comprehensive biomarker monitoring Relevant for Australian paediatric cardiology centres; apixaban availability through PBS Special Authority for paediatric indications would need consideration; aligns with RACGP guidelines supporting evidence-based anticoagulation choices Children >1 year with heart disease requiring long-term anticoagulation, particularly those transitioning from VKAs
Abstract
BACKGROUND: The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard-of-care vitamin K antagonists (VKAs) or low-molecular-weight heparin. METHODS: SAXOPHONE participants aged >1 year (n=182) had blood samples for biomarkers collected at baseline, week 2, or month 6. Participants were randomized to apixaban (n=123) or standard of care (VKA or low-molecular-weight heparin; n=59). Subgroup analyses accounted for prior VKA exposure. RESULTS: d-dimer levels decreased at month 6 in all treatment groups and remained stable during VKA-to-apixaban bridging. Apixaban significantly prolonged thrombin generation assay lag time and time to peak compared with VKAs and decreased peak thrombin similarly to VKAs in anticoagulant-naïve participants. Apixaban was associated with decreased fibrinogen and factor VIII at month 6, with no effect on protein C or S. Prior VKA exposure produced carryover effects, suppressing baseline d-dimer, thrombin generation assay parameters, and proteins C and S. CONCLUSIONS: Apixaban reduced hypercoagulability, as shown by decreased d-dimer levels and prolonged lag time, and preserved endogenous thrombin potential in thrombin generation assay, changes consistent with adult data. These findings align with SAXOPHONE's primary outcomes, supporting apixaban's favorable risk-benefit profile as a thromboprophylaxis option in children with heart disease.
References
- 1.Aborkhees, G. A., Barr, A. J., Dietrich, K., Male, C., Wang, Z., Yao, C., Payne, R. M., Glatz, A. C., Monagle, P., Burns, K. M., Reedy, A. M., Dyme, J. L., Schafer, P. H., Ajavon-Hartmann, A., & Mitchell, L. G. (2026). Ex vivo effect of apixaban on hemostatic biomarkers in children with heart disease: A SAXOPHONE trial substudy. Journal of the American Heart Association, Article e039075. https://doi.org/10.1161/JAHA.124.039075
Related Research
RMD open
Anakinra for intravenous immunoglobulin-resistant Kawasaki disease: a systematic literature review
31 July 2026
JMIR mHealth and uHealth
mHealth Technologies for the Care of Children With Congenital Heart Disease: Scoping Review
19 July 2026
BMC cardiovascular disorders
Clinical spectrum, cardiac phenotypes, and outcomes of FHL1-related cardiomyopathies: a systematic review
19 June 2026
This content is for educational purposes for healthcare professionals only and does not constitute clinical advice. Clinical decisions should be based on individual patient assessment, current guidelines, and appropriate specialist consultation. Editorial Standards · Privacy Policy · Terms of Service