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.

Keywords

electrolyte / hemoglobin / postpartum / pregnant women / venous thromboembolism

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