Clin Chem Lab Med 2015; aop Letter to the Editor Pierre Delanaye*, Bernard E. Dubois, Pierre Lukas, Pierre Peters, Jean-Marie Krzesinski, Hans Pottel and Etienne Cavalier Impact of stopping vitamin K antagonist therapy on concentrations of dephospho-uncarboxylated Matrix Gla protein DOI 10.1515/cclm-2015-0073 Received January 21, 2015; accepted February 12, 2015 To the Editor, Several experimental and clinical studies suggest that vitamin K antagonist (VKA) therapy is a risk factor for the development of vascular calcifications and calciphylaxis in hemodialysis (HD) patients [1]. One major pathophysi- ological mechanism that could explain these observations involves both vitamin K and matrix Gla protein (MGP). Briefly, MGP is an 11 kDa protein secreted by vascular smooth muscle cells, acting as a potent local inhibitor of vascular calcification. In order to be fully active, MGP must be phosphorylated and carboxylated [2]. This carboxyla- tion is highly dependent on availability of vitamin K. HD patients are per se prone to vitamin K deficiency which can be potentiated by VKA therapy. In this situation of vitamin K depletion, the MGP calcification inhibitor activ- ity is decreased leading to vascular calcification [3]. The inactive form of MGP, namely the dephospho-uncarboxy- lated MGP (dp-ucMGP), is presented as a good biomarker of vitamin K status and vascular calcification. Indeed, higher dp-ucMGP levels have been associated with higher level of vascular calcifications in CKD and HD patients [4]. To sustain the hypothesis of dp-ucMGP as a marker of vitamin K status, several authors have shown in the general population, in CKD and in HD patients that VKA therapy was associated with higher dp-ucMGP levels [4– 6]. Conversely, recent data in HD patients have shown that dp-ucMGP concentrations were decreasing after vitamin K supplementation [7–9]. Whether vitamin K therapy could be of interest in the prevention of vascular calcification in HD patients is currently under investigation [10]. Until recently, few alternative strategies were available to VKA in HD with atrial fibrillation or valve replacement. Recent data in HD suggested that fondaparinux, an indirect factor Xa inhibitor, could be safely used in these patients [11]. In the present study, we have measured dp-ucMGP in patients directly after switching from VKA to fonda- parinux. Our goal was to confirm the influence of VKA on dp-ucMGP levels and study the kinetic of these potential changes in MGP concentrations. We studied HD patients treated by VKA in our uni- versity center. These patients were all treated by aceno- coumarol. Switching from VKA to fondaparinux was considered only in patients anticoagulated for atrial fibrillation. Seven patients, dialyzed three times a week were considered. Two measurements (T1 and T2) were obtained at the beginning of the two dialysis sessions before stopping VKA. The patients stopped VKA therapy the day before the first dialysis session of the next week (on Sunday or Monday). Five measurements were then obtained at the beginning of each of the next five dialy- sis sessions (T3–T7). dp-ucMGP was quantified with an automated assay (Ina Ktif MGP iSYS kit, IDS, Boldon, UK). dp-ucMGP concentrations were compared using one-way repeated measures analysis of variance by ranks (Fried- man test), followed by Dunn’s test correcting the α-level for pairwise comparison between time-points. Mann- Whitney test was used for comparison between cohorts. Main clinical and biological characteristics of the seven patients are described in Table 1 . Before switching from VKA to fondaparinux, median concentrations of dp-ucMGP *Corresponding author: Pierre Delanaye, Service de Dialyse, CHU Sart Tilman, 4000 Liège, Belgium, Phone: +32 43667111, Fax: +32 43667205, E-mail: pierre_delanaye@yahoo.fr; and Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium Bernard E. Dubois and Jean-Marie Krzesinski: Nephrology-Dialysis- Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium Pierre Lukas, Pierre Peters and Etienne Cavalier: Clinical Chemistry, University of Liège, CHU Sart Tilman, Liège, Belgium Hans Pottel: Department of Primary Care and Public Health @ Kulak, KU Leuven Kulak, Kortrijk, Belgium Brought to you by | ULg Library Authenticated Download Date | 4/20/15 2:22 PM