scholarly journals Hepatic and Vascular Vitamin K Status in Patients with High Cardiovascular Risk

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3490
Author(s):  
Nikolas Rapp ◽  
Vincent M. Brandenburg ◽  
Nadine Kaesler ◽  
Stephan J. L. Bakker ◽  
Robert Stöhr ◽  
...  
Keyword(s):  
Vitamin K ◽  
Research Question ◽  
Coagulation Factors ◽  
Matrix Gla Protein ◽  
Weak Correlation ◽  
Vitamin K Deficiency ◽  
Disease Etiology ◽  
Cardiovascular Morbidity And Mortality ◽  
K Deficiency ◽  
Calcific Uremic Arteriolopathy

Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r2 ≤ 0.26) and distinct distribution pattern in renal and non-renal patients. In conclusion, VKA use exacerbated vitamin K deficiency across all etiologies, while vitamin K supplementation resulted in a vascular VKDP status better than that of the general population. Weak correlation of vitamin K biomarkers calls for thoughtful selection lead by the research question. Vitamin K status in non-renal deficient patients was not anomalous and may question the role of vitamin K deficiency in the pathogenesis of VC in these patients.

scholarly journals Two Types of Prothrombin in Vitamin K Deficiency

1970 ◽  
Vol 23 (03) ◽  
pp. 633-637 ◽  
Author(s):  
H. C Hemker ◽  
Annemarie D. Muller ◽  
E. A Loeliger
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulants ◽  
Coagulation Factors ◽  
The Other ◽  
Vitamin K Deficiency ◽  
Two Stage ◽  
K Deficiency

SummaryIn vitamin K deficiency (either absolute or induced by oral anticoagulants) two types of prothrombin occur. One is not distinguishable from normal prothrombin. It generates thrombin quickly in a medium in which the factors V, VII and X, thromboplastin and Ca++ are present in sufficient amounts. The other is converted into thrombin much more slowly under the same conditions. In the onestage prothrombin assay only the first form is measured, in a two-stage prothrombin assay both forms are estimated. This accounts for the well-known discrepancy between these two tests in vitamin K deficiency. The abnormal prothrombin can be considered one of the Proteins Induced by Vitamin K Absence. The occurrence of this kind of proteins fits in the concept of the action of vitamin K as a co-factor in a system that converts polypeptide-precursors into coagulation factors.

scholarly journals Vitamin K Deficiency Bleeding in Infancy

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 780
Author(s):  
Shunsuke Araki ◽  
Akira Shirahata
Keyword(s):  
Oral Administration ◽  
Vitamin K ◽  
Placental Transfer ◽  
Late Onset ◽  
Newborn Infants ◽  
Coagulation Factors ◽  
Epidemiological Studies ◽  
Vitamin K Deficiency ◽  
Vitamin K Deficiency Bleeding ◽  
K Deficiency

Vitamin K is essential for the synthesis of few coagulation factors. Infants can easily develop vitamin K deficiency owing to poor placental transfer, low vitamin K content in breast milk, and poor intestinal absorption due to immature gut flora and malabsorption. Vitamin K deficiency bleeding (VKDB) in infancy is classified according to the time of presentation: early (within 24 h), classic (within 1 week after birth), and late (between 2 week and 6 months of age). VKDB in infancy, particularly late-onset VKDB, can be life-threatening. Therefore, all infants, including newborn infants, should receive vitamin K prophylaxis. Exclusive breastfeeding and cholestasis are closely associated with this deficiency and result in late-onset VKDB. Intramuscular prophylactic injections reduce the incidence of early-onset, classic, and late-onset VKDB. However, the prophylaxis strategy has recently been inclined toward oral administration because it is easier, safer, and cheaper to administer than intramuscular injection. Several epidemiological studies have shown that vitamin K oral administration is effective in the prevention of VKDB in infancy; however, the success of oral prophylaxis depends on the protocol regimen and parent compliance. Further national surveillance and studies are warranted to reveal the optimal prophylaxis regimen in term and preterm infants.

P1645VITAMIN K DEPENDENT PROTEINS AFTER KIDNEY TRANSPLANTATION: RESULTS FROM PROSPECTIVE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Fusaro ◽  
Pascale Khairallah ◽  
Andrea Aghi ◽  
Mario Plebani ◽  
Martina Zaninotto ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Prospective Study ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Matrix Gla Protein ◽  
Bone Gla Protein ◽  
Vitamin K Deficiency ◽  
Prospective Data ◽  
K Deficiency ◽  
The Impact

Abstract Background and Aims Two Vitamin K-dependent proteins (VDKPs) link bone and vasculature in CKD-MBD: Bone Gla Protein (BGP) and Matrix Gla Protein (MGP). In ESKD, Vitamin K deficiency is highly prevalent and leads to increased levels of inactive VKDPs (undercaboxylated (ucBGP and dephosphorylated (dp)-uMGP), which are linked to greater risk of fractures and severity of vascular calcification. We hypothesized that kidney transplantation (KT) would improve Vitamin K status and lower levels of inactive VKDPs. Method Between 2014-2017, we conducted a study in 34 patients to assess changes in VKDPs during the 1st year of KT. In a specialized lab we determined VKDPs pre- and 1-year post-KT: total BGP, uc BGP, total MGP, and dp-uc MGP. We determined the prevalence of Vitamin K deficiency based on levels of uc BGP and dp-uc MGP. Results Our cohort had a mean +/- SD age of 48+/-14 years, 32% were female and 97% were Caucasian. 1 year post-KT, there was a decrease in the levels of all VKDPs and the prevalence of Vitamin K deficiency (Table 1 and Figure 1). Patients with greatest severity of Vitamin K deficiency pre-KT had the largest decreases of inactive VDKPs post-KT. Conclusion KT was associated with improvement in Vitamin K status as manifested by decreased levels of inactive VKDPs. These are the first prospective data on VKDPs in CKD patients pre- and post-KT. Studies are needed to assess the impact of improvement in VKDP status after KT on CKD-MBD outcomes.

scholarly journals Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review

2019 ◽  
Vol 20 (3) ◽  
pp. 628 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Evangelia Dounousi ◽  
Theodoros Eleftheriadis ◽  
Vassilios Liakopoulos
Keyword(s):  
Cardiovascular Disease ◽  
Renal Function ◽  
Vitamin K ◽  
Serum Levels ◽  
Matrix Gla Protein ◽  
Biologically Active ◽  
Vitamin K Deficiency ◽  
K Deficiency ◽  
Dependent Protein ◽  
Existing Data

Matrix Gla Protein (MGP), a small Gla vitamin K-dependent protein, is the most powerful natural occurring inhibitor of calcification in the human body. To become biologically active, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Vitamin K deficiency leads to the inactive uncarboxylated, dephosphorylated form of MGP (dpucMGP). We aimed to review the existing data on the association between circulating dpucMGP and vascular calcification, renal function, mortality, and cardiovascular disease in distinct populations. Moreover, the association between vitamin K supplementation and serum levels of dpucMGP was also reviewed.

scholarly journals Experimental Model of Subclinical Vitamin K Deficiency

Folia Medica ◽  
2020 ◽  
Vol 62 (2) ◽  
pp. 378-384
Author(s):  
Silvia Gancheva ◽  
Martina Kitanova ◽  
Peter Ghenev ◽  
Maria Zhelyazkova-Savova
Keyword(s):  
Vascular Calcification ◽  
Vitamin K ◽  
Coagulation Factors ◽  
Matrix Gla Protein ◽  
Severe Bleeding ◽  
Dosing Schedule ◽  
K Deficiency ◽  
Calcium Deposits ◽  
Subclinical Vitamin ◽  
High Doses

Introduction: Vitamin K (VK) is a co-factor in the post-translational gamma glutamic carboxylation of Gla-proteins. VK-dependent coagulation factors are carboxylated in the liver by VK1. Osteocalcin and Matrix-Gla protein (MGP) are carboxylated in extrahepatic tissues by VK2. A model of VK deficiency would be suitable for studying extrahepatic Gla-proteins provided that severe bleeding is prevented. Aim: The aim of this work was to adapt an established protocol of vascular calcification by warfarin-induced inactivation of MGP as a calcification inhibitor, in an attempt to create a broader state of subclinical VK deficiency and to verify its safety. Materials and methods: Two consecutive experiments, each lasting 4 weeks, were required to modify the dosing schedule of warfa­rin and VK1 and to adapt it to the Wistar rats used. The original high doses of warfarin used initially had to be halved and the protective dose of VK1 to be doubled, in order to avoid treatment-induced hemorrhagic deaths. The second experiment aimed to confirm the efficacy and safety of the modified doses. To verify the VK deficiency, blood vessels were examined histologically for calcium deposits and serum osteocalcin levels were mea­sured. Results: The original dosing schedule induced VK deficiency, manifested by arterial calcifications and dramatic changes in carboxyl­ated and uncarboxylated osteocalcin. The modified dosing regimen caused similar vascular calcification and no bleeding. Conclusion: The modified protocol of carefully balanced warfarin and VK1 doses is an effective and safe way to induce subclinical VK deficiency that can be implemented to investigate VK-dependent proteins like osteocalcin.

scholarly journals Causes of Vitamin K Deficiency in Patients on Haemodialysis

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2513
Author(s):  
Signe Wikstrøm ◽  
Katrine Aagaard Lentz ◽  
Ditte Hansen ◽  
Lars Melholt Rasmussen ◽  
Jette Jakobsen ◽  
...  
Keyword(s):  
Vitamin K ◽  
Absorption Capacity ◽  
Protein Supplementation ◽  
Matrix Gla Protein ◽  
Vitamin K1 ◽  
High Concentration ◽  
Vitamin K Deficiency ◽  
Before And After ◽  
K Deficiency ◽  
The Difference

Background: A low vitamin K status is common in patients on haemodialysis, and this is considered one of the reasons for the accelerated atherosclerosis in these patients. The vitamin is essential in activation of the protein Matrix Gla Protein (MGP), and the inactive form, dp-ucMGP, is used to measure vitamin K status. The purpose of this study was to investigate possible underlying causes of low vitamin K status, which could potentially be low intake, washout during dialysis or inhibited absorption capacity. Moreover, the aim was to investigate whether the biomarker dp-ucMGP is affected in these patients. Method: Vitamin K intake was assessed by a Food Frequency Questionnaire (FFQ) and absorption capacity by means of D-xylose testing. dp-ucMGP was measured in plasma before and after dialysis, and phylloquinine (vitamin K1) and dp-ucMGP were measured in the dialysate. Changes in dp-ucMGP were measured after 14 days of protein supplementation. Results: All patients had plasma dp-ucMGP above 750 pmol/L, and a low intake of vitamin K. The absorption capacity was normal. The difference in dp-ucMGP before and after dialysis was −1022 pmol/L (p < 0.001). Vitamin K1 was not present in the dialysate but dp-ucMGP was at a high concentration. The change in dp-ucMGP before and after protein supplementation was −165 pmol/L (p = 0.06). Conclusion: All patients had vitamin K deficiency. The reason for the low vitamin K status is not due to removal of vitamin K during dialysis or decreased absorption but is plausibly due to a low intake of vitamin K in food. dp-ucMGP is washed out during dialysis, but not affected by protein intake to a clinically relevant degree.

scholarly journals Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 351
Author(s):  
Lu Dai ◽  
Björn K. Meijers ◽  
Bert Bammens ◽  
Henriette de Loor ◽  
Leon J. Schurgers ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Vitamin K ◽  
Phosphate Binder ◽  
Microbial Metabolism ◽  
Uremic Toxins ◽  
Matrix Gla Protein ◽  
Vitamin K Deficiency ◽  
End Stage Kidney Disease ◽  
K Deficiency ◽  
End Stage

Gut microbial metabolism is not only an important source of uremic toxins but may also help to maintain the vitamin K stores of the host. We hypothesized that sevelamer therapy, a commonly used phosphate binder in patients with end-stage kidney disease (ESKD), associates with a disturbed gut microbial metabolism. Important representatives of gut-derived uremic toxins, including indoxyl sulfate (IndS), p-Cresyl sulfate (pCS), trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAG) and non-phosphorylated, uncarboxylated matrix-Gla protein (dp-ucMGP; a marker of vitamin K status), were analyzed in blood samples from 423 patients (65% males, median age 54 years) with ESKD. Demographics and laboratory data were extracted from electronic files. Sevelamer users (n = 172, 41%) were characterized by higher phosphate, IndS, TMAO, PAG and dp-ucMGP levels compared to non-users. Sevelamer was significantly associated with increased IndS, PAG and dp-ucMGP levels, independent of age, sex, calcium-containing phosphate binder, cohort, phosphate, creatinine and dialysis vintage. High dp-ucMGP levels, reflecting vitamin K deficiency, were independently and positively associated with PAG and TMAO levels. Sevelamer therapy associates with an unfavorable gut microbial metabolism pattern. Although the observational design precludes causal inference, present findings implicate a disturbed microbial metabolism and vitamin K deficiency as potential trade-offs of sevelamer therapy.

scholarly journals Functional vitamin K insufficiency, vascular calcification and mortality in advanced chronic kidney disease: A cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247623
Author(s):  
Lu Dai ◽  
Longkai Li ◽  
Helen Erlandsson ◽  
Armand M. G. Jaminon ◽  
Abdul Rashid Qureshi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Matrix Gla Protein ◽  
Vitamin K Deficiency ◽  
Increased Risk ◽  
Ckd Stage ◽  
All Cause Mortality ◽  
K Deficiency

Patients with chronic kidney disease (CKD) suffer from vitamin K deficiency and are at high risk of vascular calcification (VC) and premature death. We investigated the association of functional vitamin K deficiency with all-cause mortality and whether this association is modified by the presence of VC in CKD stage 5 (CKD G5). Plasma dephosphorylated-uncarboxylated matrix Gla-protein (dp-ucMGP), a circulating marker of functional vitamin K deficiency, and other laboratory and clinical data were determined in 493 CKD G5 patients. VC was assessed in subgroups by Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC). Backward stepwise regression did not identify dp-ucMGP as an independent determinant of VC. During a median follow-up of 42 months, 93 patients died. Each one standard deviation increment in dp-ucMGP was associated with increased risk of all-cause mortality (sub-hazard ratio (sHR) 1.17; 95% confidence interval, 1.01–1.37) adjusted for age, sex, cardiovascular disease, diabetes, body mass index, inflammation, and dialysis treatment. The association remained significant when further adjusted for CAC and AVC in sub-analyses (sHR 1.22, 1.01–1.48 and 1.27, 1.01–1.60, respectively). In conclusion, functional vitamin K deficiency associates with increased mortality risk that is independent of the presence of VC in patients with CKD G5.

Placental Transfer of Vitamin K1 and Its Implications in Fetal Hemostasis

1988 ◽  
Vol 60 (01) ◽  
pp. 039-043 ◽  
Author(s):  
L Mandelbrot ◽  
M Guillaumont ◽  
M Leclercq ◽  
J J Lefrère ◽  
D Gozin ◽  
...  
Keyword(s):  
Vitamin K ◽  
High Performance ◽  
Ultrasound Guidance ◽  
Placental Transfer ◽  
Vitamin K1 ◽  
Vitamin K Deficiency ◽  
Prothrombin Activity ◽  
Oral Supplementation ◽  
K Deficiency ◽  
The Mean

SummaryVitamin K status was evaluated using coagulation studies and/ or vitamin IQ assays in a total of 53 normal fetuses and 47 neonates. Second trimester fetal blood samples were obtained for prenatal diagnosis under ultrasound guidance. Endogenous vitamin K1 concentrations (determined by high performance liquid chromatography) were substantially lower than maternal levels. The mean maternal-fetal gradient was 14-fold at mid trimester and 18-fold at birth. Despite low vitamin K levels, descarboxy prothrombin, detected by a staphylocoagulase assay, was elevated in only a single fetus and a single neonate.After maternal oral supplementation with vitamin K1, cord vitamin K1 levels were boosted 30-fold at mid trimester and 60 fold at term, demonstrating placental transfer. However, these levels were substantially lower than corresponding supplemented maternal levels. Despite elevated vitamin K1 concentrations, supplemented fetuses and neonates showed no increase in total or coagulant prothrombin activity. These results suggest that the low prothrombin levels found during intrauterine life are not due to vitamin K deficiency.

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