scholarly journals The Effect of Vitamin K on Pivka and its Associated Procoagulant Proteins in Liver Disease

1977 ◽  
Author(s):  
R.G. Malia ◽  
F.E. Preston ◽  
E.K. Blackburn
Keyword(s):  
Liver Disease ◽  
Vitamin K ◽  
Intravenous Administration ◽  
Procoagulant Activity ◽  
Clotting Factor ◽  
Vitamin K1 ◽  
Clotting Factors ◽  
Inhibitor Activity ◽  
Normal Individuals ◽  
K Deficiency

Vitamin K deficiency is associated with low procoagulant activity of the vitamin K-dependent clotting factors together with normal concentrations of an immunologically cross-reacting protein associated with the appropriate clotting factor.In this study we have examined the response of the clotting factors II, VII and X together with their appropriate related antigens to the intravenous administration of vitamin K1 in 14 patients with various forms of liver disease. We have also related the observed changes to alterations of the inhibitor activity of PIVKA as detected by the modified thrombotest.A relationship has been established between the rate of appearance of procoagulant activity and the rate of disappearance of PIVKA after the intravenous administration of vitamin K1 in those patients with thrombotest inhibitor activity. In this same group of patients it can also be shown that PIVKA is physico-chemically dissimilar to the related protein of normal individuals.Patients without thrombotest inhibitor activity appear to synthesise decreased amounts of a structurally normal protein which is not influenced by vitamin K.

Kinetic Aspects of the Interaction of Blood Clotting Enzymes

1968 ◽  
Vol 19 (03/04) ◽  
pp. 346-363 ◽  
Author(s):  
H. C Hemker ◽  
J. J Veltkamp ◽  
E. A Loeliger
Keyword(s):  
Enzyme Kinetics ◽  
Vitamin K ◽  
Blood Clotting ◽  
Competitive Inhibitor ◽  
Clotting Factor ◽  
Clotting Factors ◽  
Vitamin K Deficiency ◽  
K Deficiency ◽  
Protein Moiety ◽  
Thrombin Formation

SummaryApplication of enzyme kinetics to the results of thrombotest estimations in correlation with specific clotting factor estimations has led to the recognition of a protein moiety that occurs in plasma in vitamin K deficiency and acts as a competitive inhibitor of thrombin formation. A hypothesis is given by which the occurrence of this inhibitor is explained in terms of a biphasic synthesis of the vitamin K-dependent clotting factors.

Vitamin K Antagonism of Coumarin Intoxication in the Rat

1986 ◽  
Vol 55 (02) ◽  
pp. 235-239 ◽  
Author(s):  
R Wallin ◽  
D Susan ◽  
D Patrick ◽  
J O Ballard
Keyword(s):  
Vitamin K ◽  
Liver Microsomes ◽  
Clotting Factor ◽  
Vitamin K1 ◽  
Clotting Factors ◽  
Strong Inhibitor ◽  
In Vitro System ◽  
High Concentrations

SummaryAn in vitro system which expresses all enzyme activities related to vitamin K-dependent carboxylation of blood clotting factors was prepared from livers of rats overdosed with warfarin, difenacoum and dicumarol respectively. In this system, the activities of the two pathways that are known to produce active reduced vitamin K1 cofactor for the carboxylation reaction were measured. Also the ability of high concentrations of vitamin Kx to overcome inhibition of clotting factor synthesis was studied. In the systems prepared from livers of warfarin and difenacoum intoxicated rats, pathway I was inactive. Vitamin K epoxide reductase was also inactive which strongly suggests that this enzyme catalyzes the activity of pathway I in vivo. Reduction of vitamin by pathway II bypassed the inactive pathway I and resulted in carboxylation activity. This pathway therefore mediates the antidotic effect of vitamin K1 in the coumarin intoxicated liver. In the in vitro system prepared from dicumarol intoxicated livers the activity of pathway I was not significantly affected. Dicumarol however was a strong inhibitor when added to liver microsomes in vitro.

scholarly journals Vitamin K a nutraceutical with impact in health

2020 ◽  
Author(s):  
Dina Simes ◽  
Carla Viegas ◽  
Nuna Araújo ◽  
Catarina Marreiros
Keyword(s):  
Vitamin K ◽  
Calcium Binding ◽  
Clinical Aspects ◽  
Vitamin K1 ◽  
Clotting Factors ◽  
Vitamin K Deficiency ◽  
Age Related ◽  
Diet Supplements ◽  
Wide Range ◽  
K Deficiency

Abstract Vitamin K has been recognized as a key factor for the synthesis of blood clotting factors in the liver, and is currently known to be involved in a wide range of biological processes and is associated with many pathological conditions.The most well-known function of vitamin K is as a cofactor for the γ-glutamyl carboxylase (GGCX) enzyme responsible for the post-translational modification of vitamin K-dependent proteins (VKDPs) through the conversion of specific glutamic acid (Glu) into calcium binding γ-carboxyglutamic acid (Gla) residues. Vitamin K deficiency has been linked to several pathological conditions such as cardiovascular diseases (CVD), chronic kidney disease (CKD), osteoarthritis (OA) , rheumatoid arthritis (RA), osteoporosis, cancer, dementia, certain skin pathologies, functional decline, and disability.  A new concept on the involvement of vitamin K in inflammation is growing. In fact, novel roles have been disclosed for vitamin K independent of its activity as a cofactor for GGCX, such as an antioxidant, anti-inflammatory, promoter of cognition, inhibition of tumor progression, and transcriptional regulator of osteoblastic genes. A growing number of studies has raised an increasing interest on the use of vitamin K as a health promoting supplement.  Aging societies represent a major economic challenge for health care systems, and diet supplements promoting healthy aging and improving the prognosis of age-related diseases, are required to be implemented in clinical practice.This work thoroughly reviews available data regarding differences between vitamin K1 and K2, contextualized with clinical aspects of vitamin K deficiency, including their sources, functions, target activity, and involvement in age-related diseases. Processes for the chemical and biological production of vitamin K1 and K2 will be briefly addressed. Additionally, novel sources with potential biotechnological application, and new formulations to improve vitamin K absorption and bioavailability are presented.

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.

Hypercoagulable State in the Watanabe Heritable Hyperlipidemic Rabbit, an Animal Model for the Progression of Atherosclerosis

1989 ◽  
Vol 61 (01) ◽  
pp. 140-143 ◽  
Author(s):  
Yoshitaka Mori ◽  
Hideo Wada ◽  
Yutaka Nagano ◽  
Katsumi Deguch ◽  
Toru Kita ◽  
...  
Keyword(s):  
Vitamin K ◽  
Fibrinogen Level ◽  
Plasma Cholesterol ◽  
Age Groups ◽  
Clotting Factor ◽  
Clotting Factors ◽  
Group A ◽  
Hyperlipidemic Rabbit ◽  
Group B ◽  
Progression Of Atherosclerosis

SummaryBlood coagulation in a strain of rabbits designated as Watanabe heritable hyperlipidemic (WHHL) rabbits was examined. The activities of vitamin K-dependent clotting factors, contact factors and clotting factor VIII (F VIII) and the fibrinogen level were significantly higher in WHHL rabbits than in normolipidemic rabbits (all age groups). Values for vitamin Independent clotting factor were already higher at 2 months of age. Contact factors and fibrinogen levels increased age after 5 to 8 months. F VIII increased between 5 and 8 months and then decreased. At 2 months of age, WHHL rabbits were divided into two groups. Group A was fed standard rabbit chow and group B standard rabbit chow containing 1% probucol. Probucol prevented the progression of atherosclerosis in group B in the absence of a significant reduction in plasma cholesterol level. F VIII and fibrinogen levels were statistically decreased in all rabbits at all ages in group B (P<0.05). These differences in clotting factors between the two groups were most obvious at 8 months (P<0.02).We conclude that vitamin K-dependent clotting factors may increase with hyperlipemia and that increases in F VIII and fibrinogen may be closely related to the progression of throm- boatherosclerosis.

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.

Increased Activity of Vitamin K-Dependent Clotting Factors in Human Hyperlipoproteinaemia – Association with Cholesterol and Triglyceride Levels

1977 ◽  
Vol 38 (02) ◽  
pp. 0465-0474 ◽  
Author(s):  
M Constantino ◽  
C Merskey ◽  
D. J Kudzma ◽  
M. B Zucker
Keyword(s):  
Vitamin K ◽  
Plasma Lipids ◽  
Coagulation Factors ◽  
Clotting Factor ◽  
Factor X ◽  
Clotting Factors ◽  
Blood Coagulation Factors ◽  
Cholesterol Levels ◽  
Type V ◽  
Increased Activity

SummaryLevels of blood coagulation factors, cholesterol and triglyceride were measured in human plasma. Prothrombin was significantly elevated in type Ha hyperlipidaemia; prothrombin and factors VII, IX and X in type lib; and prothrombin and factors VII and IX in type V. Multiple regression analysis showed significant correlation between the levels of these plasma lipids and the vitamin K-dependent clotting factors (prothrombin, factors VII, IX and X). Higher cholesterol levels were associated with higher levels of prothrombin and factor X while higher triglyceride levels were associated with higher levels of these as well as factors VII and IX. Prothrombin showed a significant cholesterol-triglyceride interaction in that higher cholesterol levels were associated with higher prothrombin levels at all levels of triglyceride, with the most marked effects in subjects with higher triglyceride levels. Higher prothrombin levels were noted in subjects with high or moderately elevated (but not low) cholesterol levels. Ultracentrifugation of plasma in a density of 1.21 showed activity for prothrombin and factors VII and X only in the lipoprotein-free subnatant fraction. Thus, a true increase in clotting factor protein was probably present. The significance of the correlation between levels of vitamin K-dependent clotting factors and plasma lipids remains to be determined.

scholarly journals Reduction of salivary tissue factor (thromboplastin) activity by warfarin therapy

Blood ◽  
1979 ◽  
Vol 53 (3) ◽  
pp. 366-374 ◽  
Author(s):  
LR Zacharski ◽  
R Rosenstein
Keyword(s):  
Tissue Factor ◽  
Vitamin K ◽  
Coagulation Factors ◽  
Human Saliva ◽  
Factor Vii ◽  
Clotting Factor ◽  
Activate Factor ◽  
Total Protein Content ◽  
Factor X ◽  
Clotting Factors

Abstract The coagulant of normal human saliva has been identified as tissue factor (thromboplastin, TF) by virtue of its ability to cause rapid coagulation in plasmas deficient in first-stage coagulation factors and to activate factor x in the presence of factor VII and by virtue of the fact that its activity is expressed only in the presence of factor VII and is inhibited by an antibody to TF. The TF is related to cells and cell fragments in saliva. Salivary TF activity has been found to be significantly reduced in patients taking warfarin. The decline in TF activity during induction of warfarin anticoagulation occurs during the warfarin-induced decline in vitamin-K-dependent clotting factor activity, as judged by the prothrombin time. The decrease in TF activity is not related to a reduction in salivary cell count or total protein content or to a direct effect of warfarin on the assay. It is hypothesized that the mechanism by which warfarin inhibits TF activity may be related to the mechanism by which it inhibits expression of the activity of the vitamin-K-dependent clotting factors. Inhibition of the TF activity may be involved in the antithrombotic effect of warfarin.

Evaluation of a Daily Dose of 25 μg Vitamin K1 to Prevent Vitamin K Deficiency in Breast-Fed Infants

1993 ◽  
Vol 16 (3) ◽  
pp. 301-305 ◽  
Author(s):  
E. A. M. Cornelissen ◽  
L. A. A. Kollée ◽  
T. G. P. J. van Lith ◽  
K. Motohara ◽  
L. A. H. Monnens
Keyword(s):  
Vitamin K ◽  
Vitamin K1 ◽  
Vitamin K Deficiency ◽  
Daily Dose ◽  
K Deficiency ◽  
Breast Fed

scholarly journals The vitamin K-dependent carboxylation system in human osteosarcoma U2-OS cells. Antidotal effect of vitamin K1 and a novel mechanism for the action of warfarin

1990 ◽  
Vol 269 (2) ◽  
pp. 459-464 ◽  
Author(s):  
R Wallin ◽  
F Rossi ◽  
R Loeser ◽  
L L Key
Keyword(s):  
Vitamin K ◽  
Hepg2 Cells ◽  
Clotting Factor ◽  
Osteosarcoma Cell ◽  
Vitamin K1 ◽  
Factor X ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
14C Labelling

An osteoblast-like human osteosarcoma cell line (U2-OS) has been shown to possess a vitamin K-dependent carboxylation system which is similar to the system in human HepG2 cells and in liver and lung from the rat. In an ‘in vitro’ system prepared from these cells, vitamin K1 was shown to overcome warfarin inhibition of gamma-carboxylation carried out by the vitamin K-dependent carboxylase. The data suggest that osteoblasts, the cells involved in synthesis of vitamin K-dependent proteins in bone, can use vitamin K1 as an antidote to warfarin poisoning if enough vitamin K1 can accumulate in the tissue. Five precursors of vitamin K-dependent proteins were identified in osteosarcoma and HepG2 cells respectively. In microsomes (microsomal fractions) from the osteosarcoma cells these precursors revealed apparent molecular masses of 85, 78, 56, 35 and 31 kDa. When osteosarcoma cells were cultured in the presence of warfarin, vitamin K-dependent 14C-labelling of the 78 kDa precursor was enhanced. Selective 14C-labelling of one precursor was also demonstrated in microsomes from HepG2 cells and from rat lung after warfarin treatment. In HepG2 cells this precursor was identified as the precursor of (clotting) Factor X. This unique 14C-labelling pattern of precursors of vitamin K-dependent proteins in microsomes from different cells and tissues reflects a new mechanism underlying the action of warfarin.

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