Is Vitamin D Deficiency Prothrombotic? A Systematic Review

Abstract

Observational studies indicate a relationship between vitamin D deficiency and an increased risk of venous and arterial thrombotic events, but the underlying mechanisms behind this association are uncertain. This systematic review explores if there is an association between decreased vitamin D levels and a prothrombotic profile. The systematic literature search initially identified 3,214 studies (published until December 21, 2021) investigating the relationship between vitamin D and numerous hemostatic parameters. After the screening process, 18 observational and intervention studies fulfilled the inclusion criteria and were included in this systematic review. Parameters of primary hemostasis, secondary hemostasis, and fibrinolysis were investigated in six, thirteen, and fifteen of these studies, respectively. Most of the eligible studies did not identify significant associations between decreased vitamin D levels and hemostatic parameters. Some conflicting results were found between decreased vitamin D levels and thrombin generation parameters and the tissue factor pathway inhibitor. Conflicting results were also found between decreased vitamin D levels and fibrinolytic parameters, although the evidence may point toward weak associations with some regulators of fibrinolysis, mostly decreased tissue type plasminogen activator. Overall, our systematic review did not identify any definitive link between vitamin D deficiency and a prothrombotic profile, which might otherwise help explain the observed association between vitamin D deficiency and increased risk of thrombotic events. Moreover, there is no clinical evidence to confirm or refute a possible antithrombotic effect of vitamin D. Larger high-quality randomized controlled trials are needed to better elucidate the link between vitamin D deficiency and a prothrombotic risk profile.

Vitamin D Deficiency is Associated With Increased Plasminogen Activator Inhibitor 1/Plasminogen Activator Inhibitor 2 Ratio in Pregnancy

“…15,51,67,72 No significant differences were shown between the 2 groups of pregnant women in the present study when comparing the additional hemostatic parameters. According to our recent systematic review, 73 findings on the effect of vitamin D on hemostatic parameters in nonpregnant populations have generally been inconclusive. However, of particular note, Blondon et al 15 suggested that the influence of vitamin D status on hemostasis may be restricted to individuals with a severe vitamin D deficiency (<25 nmol/L).…”

Editorial Compilation—XIII

“…We continue the discussion of prothrombotic pathways with the next contribution, from the authorship team of Rüdiger and colleagues, who address the question of whether Vitamin D deficiency is prothrombotic. 11 Observational studies indicate a relationship between vitamin D deficiency and an increased risk of venous and arterial thrombotic events, but the underlying mechanisms behind this association remain uncertain. The authors provide a systematic review to explore if there is an association between decreased vitamin D levels and a prothrombotic profile.…”