Role of Hemostatic Factors on the Risk of Venous Thrombosis in People With Impaired Kidney Function

Abstract

Background— Factors explaining the association between impaired kidney function and venous thrombosis have not been identified so far. The aim of our study was to determine whether the association between impaired kidney function and venous thrombosis can be explained by the concurrent presence of genetic or acquired venous thrombosis risk factors. Methods and Results— The glomerular filtration rate was estimated (eGFR) in 2473 venous thrombosis patients and 2936 controls from a population-based case–control study. Kidney function was grouped into 6 categories based on percentiles of the eGFR in the controls (>50th [reference], 10th–50th, 5th–10th, 2.5th–5th, 1st–2.5th, and <1st percentile). Several hemostatic factors showed a procoagulant shift with decreasing kidney function in controls, most notably factor VIII and von Willebrand factor. Compared with eGFR >50th percentile, factor VIII levels (adjusted mean difference, 60 IU/dL for the <1st eGFR percentile category) and von Willebrand factor levels (adjusted mean difference, 60 IU/dL for the <1st eGFR percentile category) increased with each percentile category. The odds ratios for venous thrombosis similarly increased across the categories from 1.1 (95% confidence interval, 0.9–1.3) for the 10th to 50th percentile to 3.7 (95% confidence interval, 2.4–5.7) for the <1st percentile category. Adjustment for factor VIII or von Willebrand factor attenuated these odds ratios, indicating an effect of eGFR on thrombosis through these factors. Adjustments for other risk factors for venous thrombosis did not affect the odds ratios. Conclusion— Impaired kidney function affects venous thrombosis risk via concurrently raised factor VIII and von Willebrand factor levels.