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Thromb Haemost 2024; 124(12): 1117-1133
DOI: 10.1055/a-2330-1371
Stroke, Systemic or Venous Thromboembolism

Circulating Blood Biomarkers and Risk of Venous Thromboembolism in Cancer Patients: A Systematic Review and Meta-Analysis

Danielle Carole Roy 
1   Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
,
Tzu-Fei Wang
1   Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
2   Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
3   The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Ronda Lun
2   Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
3   The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
4   Vascular Neurology, Stanford Healthcare, Palo Alto, California, United States
,
Amin Zahrai
1   Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
3   The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Ranjeeta Mallick
3   The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Dylan Burger
2   Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
3   The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Gabriele Zitikyte
5   Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
,
Steven Hawken   *
1   Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
3   The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
,
Philip Wells   *
1   Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
2   Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
3   The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
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Abstract

Background Cancer patients have an increased risk of venous thromboembolism (VTE). Currently, the availability of highly discriminatory prediction models for VTE in cancer patients is limited. The implementation of biomarkers in prediction models might lead to refined VTE risk prediction. In this systematic review and meta-analysis, we aimed to evaluate candidate biomarkers and their association with cancer-associated VTE.

Methods We searched Medline, EMBASE, and Cochrane Central for studies that evaluated biomarkers in adult cancer patients from inception to September 2022. We included studies reporting on VTE after a cancer diagnosis with biomarker measurements performed at a defined time point. Median/mean differences (for continuous measures) and odds ratios (for dichotomous measures) with 95% confidence intervals were estimated and pooled using random-effects models.

Results We included 113 studies in the systematic review. Of these, 50 studies were included in the meta-analysis. We identified two biomarkers at cancer diagnosis (factor VIII and time to peak thrombin), three biomarkers pre-chemotherapy (D-dimer, fibrinogen, and mean platelet volume), and one biomarker preoperatively (platelet count) that had significant median or mean differences. Additionally, we found that hemoglobin <100 g/L and white blood count >11 × 109/L were significantly associated with future VTE risk only when measured at cancer diagnosis. Pre-chemotherapy neutrophil-to-lymphocyte ratio ≥3 and preoperative platelet count ≥400 × 109/L were also found to be associated with future VTE risk.

Conclusion In conclusion, this study identified nine candidate blood biomarkers that may help in optimizing VTE prediction in cancer patients that should be further explored in future studies.

Keywords

venous thromboembolism - biomarkers - cancer - systematic review - meta-analysis

Data Availability Statement

Corresponding author for the article has access to all the data and takes responsibility for the analyses conducted as part of this study.


Authors' Contribution

D.C.R., T.-F.W., R.M., and P.W. designed the research question. D.C.R., T.-F.W., A.Z., R.M., and P.W. designed the eligibility criteria and the screening strategy. D.C.R., T.-F.W., R.L., A.Z., R.M., P.W., and S.H. came up with the data extraction items. D.C.R., T.-F.W., A.Z., R.M., and P.W. developed the data synthesis strategy. D.C.R., T.-F.W., A.Z., R.M., and P.W. drafted the protocol manuscript, and it was reviewed and approved by all authors. D.C.R. and R.L. extracted the data. D.C.R., R.M., G.Z., and S.H. aided with data analysis. D.C.R. and G.Z. completed the ROB assessments. D.C.R., T.-F.W., R.M., D.B., S.H., and P.W. interpreted the results. All authors reviewed the results, proofread and approved the final version of the manuscript.


* These authors are co-senior authors.


Supplementary Material



Publikationsverlauf

Eingereicht: 18. Oktober 2023

Angenommen: 19. Mai 2024

Accepted Manuscript online:
20. Mai 2024

Artikel online veröffentlicht:
12. Juni 2024

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