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

Abstract

Background Vitamin D deficiency has recently been suggested as an independent risk factor for thrombosis. Notably, vitamin D deficiency is common in pregnant populations, whom already have an increased thrombotic risk. However, pregnant women are commonly excluded from studies investigating the hemostatic system, and knowledge on the impact of vitamin D on hemostasis in pregnancy is therefore limited. Methods A cross-sectional study comparing the hemostatic profile of pregnant women (gestational week 12.9 ± 0.7) with vitamin D deficiency (≤50 nmol/L) (n = 70) and high adequate vitamin D status (≥100 nmol/L) (n = 59). Results Vitamin D deficient women displayed increased plasminogen activator inhibitor 1 levels and an increased plasminogen activator inhibitor 1/plasminogen activator inhibitor 2 ratio, even after adjusting for factors with potential influence on hemostasis (body mass index, smoking and use of fish oil supplements). Conclusions Vitamin D deficiency is associated with increased plasminogen activator inhibitor 1/plasminogen activator inhibitor 2 ratio in pregnant women. As an increased plasminogen activator inhibitor 1/plasminogen activator inhibitor 2 ratio with high plasminogen activator inhibitor 1 levels may increase thrombotic risk and is associated with the development of pregnancy complications, further research is needed to determine the optimal vitamin D supplementation in pregnancy.

Vitamin D Status in Patients with Primary Antiphospholipid Syndrome (PAPS): A Systematic Review and Meta-Analysis

“…To elucidate this phenomenon, a theoretical framework known as the “two-hit” hypothesis has been adopted to account for thrombosis [ 7 ]. The initial “first hit” refers to the existence of aPLs that are recognised for their ability to facilitate thrombosis via various mechanisms and the deficiency of vitamin D may potentially serve as an additional “second hit” for thrombotic events, supported by reports in multiple studies [ 8 , 9 , 10 , 11 ]. The deficiency of vitamin D initiates the activation of two crucial components involved in blood coagulation, namely tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) [ 9 , 11 , 12 ].…”

“…The initial “first hit” refers to the existence of aPLs that are recognised for their ability to facilitate thrombosis via various mechanisms and the deficiency of vitamin D may potentially serve as an additional “second hit” for thrombotic events, supported by reports in multiple studies [ 8 , 9 , 10 , 11 ]. The deficiency of vitamin D initiates the activation of two crucial components involved in blood coagulation, namely tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) [ 9 , 11 , 12 ]. In addition, vitamin D deficiency has been shown to decrease the formation of thrombomodulin, a glycoprotein with anticoagulant properties [ 10 ].…”