Pathophysiology of Vitamin K-deficiency and Oral Anticoagulants

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.

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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 ◽

10.3390/fermentation7040202 ◽

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.

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Vitamin K and Bone Health: A Review on the Effects of Vitamin K Deficiency and Supplementation and the Effect of Non-Vitamin K Antagonist Oral Anticoagulants on Different Bone Parameters

Journal of Osteoporosis ◽

10.1155/2019/2069176 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Celia Rodríguez-Olleros Rodríguez ◽

Manuel Díaz Curiel

Keyword(s):

Vitamin K ◽

Bone Health ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Coagulation Cascade ◽

Undercarboxylated Osteocalcin ◽

Vitamin K Deficiency ◽

Risk Of Fracture ◽

K Deficiency ◽

Related Proteins

Although known for its importance in the coagulation cascade, vitamin K has other functions. It is an essential vitamin for bone health, taking part in the carboxylation of many bone-related proteins, regulating genetic transcription of osteoblastic markers, and regulating bone reabsorption. Vitamin K deficiency is not uncommon, as deposits are scarce and dependent upon dietary supplementation and absorption. Vitamin K antagonist oral anticoagulants, which are prescribed to many patients, also induce vitamin K deficiency. Most studies find that low serum K1 concentrations, high levels of undercarboxylated osteocalcin (ucOC), and low dietary intake of both K1 and K2 are associated with a higher risk of fracture and lower BMD. Studies exploring the relationship between vitamin K supplementation and fracture risk also find that the risk of fracture is reduced with supplements, but high quality studies designed to evaluate fracture as its primary endpoint are needed. The reduction in risk of fracture with the use of non-vitamin K antagonist oral anticoagulants instead of warfarin is also of interest although once again, the available evidence offers disparate results. The scarce and limited evidence, including low quality studies reaching disparate conclusions, makes it impossible to extract solid conclusions on this topic, especially concerning the use of vitamin K supplements.

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Placental Transfer of Vitamin K1 and Its Implications in Fetal Hemostasis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647631 ◽

1988 ◽

Vol 60 (01) ◽

pp. 039-043 ◽

Cited By ~ 52

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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Kinetic Aspects of the Interaction of Blood-Clotting Enzymes

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651250 ◽

1968 ◽

Vol 20 (01/02) ◽

pp. 078-087 ◽

Cited By ~ 34

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.

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Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657025 ◽

1979 ◽

Vol 42 (04) ◽

pp. 1296-1305 ◽

Cited By ~ 29

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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