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

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 x 10(9)/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 x 10(9)/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.