The effects of discontinuation of vitamin K antagonists on the rate of elastin degradation

Elastin is a unique protein providing elasticity, resilience and deformability
to dynamic tissues, such as lungs and vasculature. Elastin fibers are
characterized by their high affinity for calcium. However, calcified elastin is
more prone to the degrading effects of proteases and, in turn, partially
degraded elastin has an even higher affinity for calcium. A disturbed balance
between proteases and anti-proteases is a major underlying mechanism in the
development of chronic obstructive pulmonary disease (COPD). Virtually the only
protein that can protect elastin from calcification is matrix Gla-protein
(MGP), which needs vitamin K for its activation. In COPD patients, a lower
vitamin K status is found when compared to control subjects and an inverse
association exists between vitamin K status and elastin degradation. In
addition, vitamin K status is lower and elastin degradation is accelerated in
VKA users.
Vitamin K antagonists (VKAs) are widely used. Nowadays, an increasing number of
patients uses direct oral anticoagulants (DOACs), which do not influence
vitamin K status. We hypothesize that discontinuation of VKAs results in an
improved vitamin K status and deceleration of elastin degradation. In order to
test this hypothesis, we want to conduct an observational study in which the
change in elastin degradation* quantified by plasma desmosine concentrations *
in patients who discontinue use of VKAs will be used as primary endpoint.

To evaluate whether discontinuation of VKAs results in a higher vitamin K
status and deceleration of the rate of mature cross-linked elastin degradation.

Observational study

We will draw extra blood collection tubes at two moments. The first time is
during one of the last regular INR testing at the anticoagulation clinic,
therefore no additional venipuncture has to be performed. At this moment two
additional blood collection tubes will be drawn. The second moment is
approximately 6 months after discontinuation of VKAs. At this point the patient
will undergo an additional venipuncture. Patients are asked to fill in a
questionnaire concerning age, gender, length, height, indication for VKA use,
duration of VKA use, smoking status and history, presence of COPD and other
pulmonary disease, vitamin D supplementation and use of medications.
Furthermore, we will record the INR at baseline. Participants may experience
some discomfort during blood sampling. Participating in the study has
negligible risks.