A Low Serum Calcium‐to‐Potassium Ratio Predicts Postpartum Venous Thromboembolism Risk: Mediation by Hemoglobin and D‐Dimer in a Multicenter Cohort

ABSTRACT

Postpartum venous thromboembolism (VTE) is a serious complication, and electrolytes may play a role in coagulation homeostasis, but their associations with postpartum VTE remain unclear. A total of 25,792 pregnant women from Chinese multicenter cohort between January 2017 and December 2024 were included, and the occurrences of postpartum VTE within 6 weeks after delivery were followed. Here, we show that dysregulated perinatal electrolyte profiles and a reduced serum calcium (Ca) /potassium (K) ratio are novel and independent risk factors for postpartum VTE, with hemoglobin and D‐dimer levels mediating such associations. Restricted cubic spline analyses showed that low serum Ca (overall association p = 0.032) and high serum K (overall association p = 0.036) were associated with increased postpartum VTE risk. Serum magnesium exhibited a nonlinear inverse U‐shaped association with VTE risk (nonlinear p = 0.021). Low serum Ca/K ratio was linked to elevated VTE risk (overall association p = 0.004), with a nonlinear relationship (nonlinear p = 0.042) and an inflection point at 0.55. Notably, a serum Ca/K ratio below 0.55 is a promising new biomarker for predicting the risk of postpartum VTE. Mediation analyses suggested that the protective effect of a higher Ca/K ratio might be partially explained by its association with higher hemoglobin levels (34.7% mediation, p = 0.036) and lower D‐dimer levels (4.6% mediation, p = 0.018). This study suggests that strategies aimed at optimizing perinatal electrolyte balance and the monitoring and management of anemia may help reduce the burden of postpartum VTE.