Laboratory assessment of vitamin K status

2019 ◽  
Vol 73 (2) ◽  
pp. 70-75 ◽  
Author(s):  
David John Card ◽  
Renata Gorska ◽  
Dominic Jon Harrington
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
The Elderly ◽  
Vitamin K Deficiency ◽  
Laboratory Assessment ◽  
Increased Risk ◽  
K Deficiency ◽  
Gla Domain ◽  
Insight Into ◽  
Abbott Architect

Vitamin K is required for the ɣ-carboxylation of specific glutamic acid residues within the Gla domain of the 17 vitamin K-dependent proteins (VKDPs). The timely detection and correction of vitamin K deficiency can protect against bleeding. Vitamin K also plays a role in bone metabolism and vascular calcification. Patients at increased risk of vitamin K deficiency include those with a restricted diet or malnutrition, lipid malabsorption, cancer, renal disease, neonates and the elderly. Coagulation assays such as the prothrombin time have been used erroneously as indicators of vitamin K status, lacking sufficient sensitivity and specificity for this application. The measurement of phylloquinone (K1) in serum is the most commonly used marker of vitamin K status and reflects abundance of the vitamin. Concentrations <0.15 µg/L are indicative of deficiency. Disadvantages of this approach include exclusion of the other vitamin K homologues and interference from recent dietary intake. The cellular utilisation of vitamin K is determined through measurement of the prevalence of undercarboxylated VKDPs. Most commonly, undercarboxylated prothrombin (Protein Induced by Vitamin K Absence/antagonism, PIVKA-II) is used (reference range 17.4–50.9 mAU/mL (Abbott Architect), providing a retrospective indicator of hepatic vitamin K status. Current clinical applications of PIVKA-II include supporting the diagnosis of vitamin K deficiency bleeding of the newborn, monitoring exposure to vitamin K antagonists, and when used in combination with α-fetoprotein, as a diagnostic marker of hepatocellular carcinoma. Using K1 and PIVKA-II in tandem is an approach that can be used successfully for many patient cohorts, providing insight into both abundance and utilisation of the vitamin.

Vitamin K deficiency: an emerging player in the pathogenesis of vascular calcification and an iatrogenic consequence of therapies in advanced renal disease

2020 ◽  
Vol 319 (4) ◽  
pp. F618-F623
Author(s):  
David S. Levy ◽  
Rickinder Grewal ◽  
Thu H. Le
Keyword(s):  
Bone Metabolism ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Hospital Admissions ◽  
Fibroblast Growth Factor 23 ◽  
Vitamin K Deficiency ◽  
Increased Risk ◽  
K Deficiency ◽  
Human Aortic Valve

Vascular calcification is a known complication of chronic kidney disease (CKD). The prevalence of vascular calcification in patients with non-dialysis-dependent CKD stages 3–5 has been shown to be as high as 79% ( 20 ). Vascular calcification has been associated with increased risk for mortality, hospital admissions, and cardiovascular disease ( 6 , 20 , 50 , 55 ). Alterations in mineral and bone metabolism play a pivotal role in the pathogenesis of vascular calcification in CKD. As CKD progresses, levels of fibroblast growth factor-23, parathyroid hormone, and serum phosphorus increase and levels of 1,25-(OH)2 vitamin D decrease. These imbalances have been linked to the development of vascular calcification. More recently, additional factors have been found to play a role in vascular calcification. Matrix G1a protein (MGP) in its carboxylated form (cMGP) is a potent inhibitor of vascular calcification. Importantly, carboxylation of MGP is dependent on the cofactor vitamin K. In patients with CKD, vitamin K deficiency is prevalent and is exacerbated by warfarin, which is frequently used for anticoagulation. Insufficient bioavailability of vitamin K reduces the amount of cMGP available, and, therefore, it may lead to increased risk of vascular calcification. In vitro studies have shown that in the setting of a high-phosphate environment and vitamin K antagonism, human aortic valve interstitial cells become calcified. In this article, we discuss the pathophysiological consequence of vitamin K deficiency in the setting of altered mineral and bone metabolism, its prevalence, and clinical implications in patients with CKD.

scholarly journals Vitamin K in COVID-19—Potential Anti-COVID-19 Properties of Fermented Milk Fortified with Bee Honey as a Natural Source of Vitamin K and Probiotics

Fermentation ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 202
Author(s):  
Amira Mohammed Ali ◽  
Hiroshi Kunugi ◽  
Hend A. Abdelmageed ◽  
Ahmed S. Mandour ◽  
Mostafa Elsayed Ahmed ◽  
...  
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Empirical Studies ◽  
Fermented Milk ◽  
Organ Damage ◽  
Natural Source ◽  
Vitamin K Deficiency ◽  
K Deficiency

Vitamin K deficiency is evident in severe and fatal COVID-19 patients. It is associated with the cytokine storm, thrombotic complications, multiple organ damage, and high mortality, suggesting a key role of vitamin K in the pathology of COVID-19. To support this view, we summarized findings reported from machine learning studies, molecular simulation, and human studies on the association between vitamin K and SARS-CoV-2. We also investigated the literature for the association between vitamin K antagonists (VKA) and the prognosis of COVID-19. In addition, we speculated that fermented milk fortified with bee honey as a natural source of vitamin K and probiotics may protect against COVID-19 and its severity. The results reported by several studies emphasize vitamin K deficiency in COVID-19 and related complications. However, the literature on the role of VKA and other oral anticoagulants in COVID-19 is controversial: some studies report reductions in (intensive care unit admission, mechanical ventilation, and mortality), others report no effect on mortality, while some studies report higher mortality among patients on chronic oral anticoagulants, including VKA. Supplementing fermented milk with honey increases milk peptides, bacterial vitamin K production, and compounds that act as potent antioxidants: phenols, sulforaphane, and metabolites of lactobacilli. Lactobacilli are probiotic bacteria that are suggested to interfere with various aspects of COVID-19 infection ranging from receptor binding to metabolic pathways involved in disease prognosis. Thus, fermented milk that contains natural honey may be a dietary manipulation capable of correcting nutritional and immune deficiencies that predispose to and aggravate COVID-19. Empirical studies are warranted to investigate the benefits of these compounds.

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.

Prothrombin And Abnormal (Des-γ-Carboxy) Prothrombin: Assessment Of Plasma Levels By Ria In Disorders Of Hepatic Vitamin K-Dependent Carboxylation

1981 ◽  
Author(s):  
R A Blanchard ◽  
B C Furie ◽  
S F Kruger ◽  
B Furie
Keyword(s):  
Liver Disease ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Vitamin K Deficiency ◽  
Amino Terminal ◽  
Disease States ◽  
Carboxyglutamic Acid ◽  
Precursor Proteins ◽  
Before And After ◽  
K Deficiency

The vitamin K-dependent blood coagulation zymogens contain γ-carboxyglutamic acid (Gla) in their amino terminal domains. The presence of these Gla residues is necessary for the physiologic activation of these zymogens to proteases. The Gla residues are synthesized from glutamic acids on precursor proteins in the liver by a vitamin K-dependent carboxylase. In treatment with vitamin K antagonists or in the presence of vitamin K-deficiency carboxylation is impaired and des-γ-carboxy forms circulate in the blood. We have developed specific RIAs for human prothrombin (NPT) and for des-γ-carboxy human prothrombin (APT) to evaluate the levels of these species in human plasma. These plasma assays measure only NPT despite the presence of APT or only APT despite the presence of NPT.These results suggest that total prothrombin synthesis is decreased in patients treated with warfarin and in patients with intrinsic liver disease compared to normals or to vitamin K-deficient patients. APT is not a component of normal plasma (>0.03 g/ml). However APT is present in 90% of the patients with intrinsic liver disease. In ten patients with liver disease in whom samples were obtained before and after vitamin K administration APT persisted in the plasma. This indicates impaired vitamin-K-dependent car-boxylation in these disorders. We feel that the patterns of plasma NPT and APT in these disease states are characteristic and may prove useful in identifying and distinguishing liver disease from disorders of PT biosynthesis.

Vitamin K Deficiency in the Elderly

1970 ◽  
Vol 12 (1) ◽  
pp. 10-17 ◽  
Author(s):  
K. Hazell ◽  
K.H. Baloch
Keyword(s):  
Vitamin K ◽  
The Elderly ◽  
Vitamin K Deficiency ◽  
K Deficiency

The Impact Of Dietary Vitamin K On The Pharmacological Activity Of FXa Inhibitor, Rivaroxaban, In Man

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4808-4808
Author(s):  
Farhad Kamali ◽  
Salah Abohelaika ◽  
Tina T. Biss ◽  
Judith Coulson ◽  
Hilary Wynne ◽  
...  
Keyword(s):  
Vitamin K ◽  
Pharmacological Activity ◽  
Healthy Subjects ◽  
The Elderly ◽  
Dietary Vitamin ◽  
Elderly Subjects ◽  
Vitamin K Deficiency ◽  
K Deficiency ◽  
The Mean ◽  
The Impact

Introduction/Background Over several decades, warfarin has been used as the drug of choice for prevention and treatment of thromboembolic disorders. The impact of dietary vitamin K intake on anticoagulation response to warfarin is well established. However, the effect of dietary vitamin K on the activity of the novel oral anticoagulants is less well known. Since the activation of both factor X and thrombin is inextricably linked to the vitamin K cycle in the coagulation cascade, there is the possibility that the pharmacological activity of agents that inhibit these proteins could be influenced by alterations in vitamin K availability. Aim To examine the influence of dietary vitamin K intake on the pharmacological activity of rivaroxaban in man. Methods The pharmacological activity of rivaroxaban was evaluated ex-vivo. Thirty one medically stable elderly inpatients (12 males) with a poor dietary intake in terms of calories and nutrients including vitamin K (12 males) and 28 healthy subjects (7 males) with adequate diets were enrolled into the study. An overnight fasted venous blood sample (20 ml) was taken from each subject. The plasma was stored at -80 degree C for the later measurement of the effects of rivaroxaban on clotting times and clotting factor activity. Each subject completed a validated dietary questionnaire for quantification of vitamin K content of foods eaten in the past week. The plasma samples from each subject were incubated with a range of rivaroxaban concentrations (100 - 500 ng/ml) in order to simulate the therapeutic drug plasma concentrations. Normal prothrombin time (PT), modified prothrombin time (mPT), and vitamin K dependent clotting factors activity were measured according to established in-house methods. Results The mean±SD age of elderly patients and healthy subjects was 87±6 and 36±10 years, respectively. Rivaroxaban produced a greater prolongation of both PT (P=0.01) and m-PT (P=0.02) in the plasma of elderly subjects than the younger healthy subjects over the drug concentration range studied. The mean difference in PT between the two groups ranged from 1.8s to 5.0s at 100 ng/ml and 500 ng/ml plasma rivaroxaban concentrations respectively. The mean difference in m-PT between the two groups ranged from 10.0s to 34.0s at 100 ng/ml and 500 ng/ml plasma rivaroxaban concentrations respectively. There was also a greater inhibition of factor Xa (P=0.005) activity by rivaroxaban in the elderly subjects compared to the healthy subjects, whereas factor IXa (P=0.03) activity was significantly inhibited in the healthy subjects compared to the elderly subjects. However, there were no significant differences between the two groups in factors II and VII activity and fibrinogen concentration. The analysis of dietary questionnaires for vitamin K intake and plasma for fasting vitamin K levels is in progress and the results will be presented. Conclusion We have previously demonstrated in a proof-of-concept study in rats that vitamin K deficiency significantly enhanced the pharmacological activity of the prototype DTI, ximelagatran [1]. The present study findings suggest that the anticoagulation response to rivaroxaban may be influenced by poor dietary vitamin K intake. Assessment of whether dietary vitamin K influences anticoagulation response as well as any influence of age, co morbidities and drug intake in patients taking rivaroxaban is warranted. [1] Kamali F, Wood P, Ward A. Vitamin K deficiency amplifies anticoagulation response to ximelagatran: possible implications for direct thrombin inhibitors and their clinical safety. Annals of Hematology 2009; 88:141-149. Disclosures: No relevant conflicts of interest to declare.

A study of the prevalence of vitamin K deficiency in patients with cancer referred to a hospital palliative care team and its association with abnormal haemostasis

2007 ◽  
Vol 61 (4) ◽  
pp. 537-540 ◽  
Author(s):  
D J Harrington ◽  
H Western ◽  
C Seton-Jones ◽  
S Rangarajan ◽  
T Beynon ◽  
...  
Keyword(s):  
Palliative Care ◽  
Advanced Cancer ◽  
Vitamin K ◽  
Liver Function Tests ◽  
Vitamin K Deficiency ◽  
Patients With Cancer ◽  
Increased Risk ◽  
K Deficiency ◽  
Clinically Significant ◽  
Patients Experience

Background:Many patients with advanced cancer are malnourished. Anorexia is common, as is the use of chemotherapy, which may cause nausea and poor appetite. Ten per cent of these patients experience haemorrhagic events.Aim:Since vitamin K deficiency (VKD) causes bleeding, to establish the prevalence of VKD in patients with advanced cancer receiving palliative care.Methods:Serum concentrations of vitamin K1 and undercarboxylated factor II (PIVKA-II) were determined in 46 (17 male/29 female) inpatients aged 26–85 (mean 58) years. INR and liver function tests (bilirubin, ALT, GGT and ALP) were also performed.Results:Vitamin K1 was below the lower limit of the reference range (0.33 nmol/l) in 22% of patients. 78% of patients had some degree of functional VKD indicated by raised (>0.2 AU/ml) PIVKA-II. Six patients (13%) had a prolonged INR, all of whom had raised PIVKA-II and GGT; 4 also had vitamin K1 <0.33 nmol/l. Three patients (6.5%) had clinically significant VKD characterised by INR >1.5, PIVKA-II >10 AU/ml, and undetectable vitamin K1.Conclusions:Patients with advanced cancer are prone to VKD which, while usually subclinical, may develop to a clinically relevant prolongation of the INR. Serum measurements of vitamin K1 and PIVKA-II can be used to detect VKD and monitor vitamin K status before an increased risk of bleeding develops.

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.

Kinetic Aspects of the Interaction of Blood-Clotting Enzymes

1968 ◽  
Vol 20 (01/02) ◽  
pp. 078-087 ◽  
Author(s):  
H. C Hemker ◽  
A. D Muller
Keyword(s):  
Vitamin K ◽  
Blood Clotting ◽  
Experimental Results ◽  
Factor X ◽  
Clotting Factors ◽  
Vitamin K Deficiency ◽  
K Deficiency

SummaryPIVKA, the circulating anticoagulant protein found in vitamin K deficiency can, on kinetical grounds, be recognized as an analogue of factor X. The existence of analogues of other vitamin K-dependent clotting factors cannot be ruled out, but need not be assumed to explain the experimental results.

Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

1979 ◽  
Vol 42 (04) ◽  
pp. 1296-1305 ◽  
Author(s):  
R M Bertina ◽  
W van der Marel-van Nieuwkoop ◽  
E A Loeliger
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Oral Anticoagulation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Factor V ◽  
Anticoagulant Treatment ◽  
Factor Ii ◽  
K Deficiency

SummaryTwo spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

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