Background: Several studies have explored the association between alkaline phosphatase (ALP) and venous thromboembolism (VTE), yet the findings remain inconclusive and inconsistent. The correlation between them has yet to be definitively established. We conducted a multicenter cohort study and a two-sample Mendelian randomization (MR) analysis with the aim of investigating the association between serum ALP levels and acute VTE in East Asian populations.

Methods: We collected data on VTE patients from Taizhou Municipal Hospital and Taizhou Hospital of Zhejiang Province between January 2019 and October 2024, alongside data from routine health check-up participants as the control group. Employing propensity score matching (PSM) and cubic spline model analysis, we investigated the relationship between ALP levels and VTE. Additionally, we performed a bidirectional two-sample MR analysis using genome-wide association study (GWAS) data to assess the potential causal effect between them.

Results: The retrospective cohort study involving 720 VTE patients and 1000 healthy controls found significantly lower ALP levels in the VTE group, which remained consistent after propensity score matching, with a non-linear relationship between ALP levels and VTE risk. Two-sample MR analysis confirmed a negative causal effect of ALP on VTE, with no evidence of pleiotropy in the results.

Conclusions: Our study suggested a negative association between ALP levels and the risk of VTE in the East Asian population. This finding may provide valuable insights into the role of ALP as a potential biomarker for VTE risk assessment.