scholarly journals Intravenous Vitamin K1 for the Correction of Prolonged Prothrombin Times in Non-Bleeding Critically Ill Patients: A Prospective Observational Study

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2580
Author(s):  
Sofia Dahlberg ◽  
Ulf Schött ◽  
Emilia Ängeby Eriksson ◽  
Yllnor Tahirsylaj ◽  
Leon Schurgers ◽  
...  
Keyword(s):  
Critically Ill ◽  
Vitamin K ◽  
Critically Ill Patients ◽  
Thrombin Generation ◽  
Coagulation Factors ◽  
Matrix Gla Protein ◽  
Vitamin K1 ◽  
Clotting Factors ◽  
Short And Long Term ◽  
Intravenous Vitamin

The aim of this study was to evaluate the effects of vitamin K1 on various vitamin K-dependent proteins in critically ill patients with prolonged Owren PT. We included critically ill non-bleeding adult patients without liver failure or anticoagulation treatment, with Owren PT > 1.2, who were prescribed intravenous vitamin K1. Blood was drawn at baseline and at 20–28 h after vitamin K1 administration. At both time points, we measured various vitamin K-dependent proteins and coagulation assays. ClinicalTrials.gov; Identifier: NTC3782025. In total, 52 patients were included. Intravenous vitamin K1 reduced Owren PT, Quick PT, protein induced by vitamin K absence/antagonist-II and desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), but not to normal levels. Concomitantly, there were increases in thrombin generation and the activity of coagulation factors II, VII, IX and X that was only counteracted with a small increase in Protein C activity. In conclusion, the results suggest that vitamin K1 strengthens coagulation as measured by PT decrease and increases in the activity of vitamin K-dependent clotting factors and thrombin generation. The decreased dp-ucMGP, and its potential positive short- and long-term non-coagulative effects, merits further research.

scholarly journals Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects

2012 ◽  
Vol 108 (9) ◽  
pp. 1652-1657 ◽  
Author(s):  
Elke Theuwissen ◽  
Ellen C. Cranenburg ◽  
Marjo H. Knapen ◽  
Elke J. Magdeleyns ◽  
Kirsten J. Teunissen ◽  
...  
Keyword(s):  
Vitamin K ◽  
Statistical Power ◽  
Thrombin Generation ◽  
Low Dose ◽  
Coagulation Factors ◽  
Peak Height ◽  
Matrix Gla Protein ◽  
High Dose ◽  
Age Related ◽  
Intervention Trials

Vitamin K is required for the carboxylation of Gla-proteins in the liver (coagulation factors) and extra-hepatic tissues, such as bone (osteocalcin, OC), and arterial wall (matrix Gla-protein, MGP). Although the coagulation factors are essentially fully carboxylated under normal conditions, 10–40 % of OC and MGP remains undercarboxylated. We were therefore interested to study the dose–response effects of extra intake of menaquinones on the carboxylation of the extra-hepatic Gla-proteins. A total of forty-two healthy Dutch men and women aged between 18 and 45 years were randomised into seven groups to receive: placebo capsules or menaquinone-7 (MK-7) capsules at a daily dose of 10, 20, 45, 90, 180 or 360 μg. Circulating uncarboxylated OC (ucOC), carboxylated OC (cOC) and desphospho-uncarboxylated MGP were measured by ELISA. The ucOC:cOC ratio was calculated from circulating ucOC and cOC values. Endogenous thrombin potential and peak height were determined by calibrated automated thrombography. To increase the statistical power, we collapsed the treatment groups into three dosage groups: placebo, low-dose supplementation (doses below RDA, Commission Directive 2008/100/EC), and high-dose supplementation (doses around RDA, Commission Directive 2008/100/EC). MK-7 supplementation at doses in the order of the RDA (Commission Directive 2008/100/EC) increased the carboxylation of circulating OC and MGP. No adverse effects on thrombin generation were observed. Extra MK-7 intake at nutritional doses around the RDA (Commission Directive 2008/100/EC) improved the carboxylation of the extra-hepatic vitamin K-dependent proteins. Whether this improvement contributes to public health, i.e. increasing the protection against age-related diseases needs further investigation in specifically designed intervention trials.

Vitamin K–containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7

Blood ◽  
2006 ◽  
Vol 109 (8) ◽  
pp. 3279-3283 ◽  
Author(s):  
Leon J. Schurgers ◽  
Kirsten J. F. Teunissen ◽  
Karly Hamulyák ◽  
Marjo H. J. Knapen ◽  
Hogne Vik ◽  
...  
Keyword(s):  
Vitamin K ◽  
Serum Vitamin ◽  
Life Time ◽  
Serum Levels ◽  
Coagulation Factors ◽  
Matrix Gla Protein ◽  
Vitamin K1 ◽  
Blood Coagulation Factors ◽  
Oral Anticoagulant Treatment ◽  
Over The Counter

Abstract Vitamin K is a cofactor in the production of blood coagulation factors (in the liver), osteocalcin (in bone), and matrix Gla protein (cartilage and vessel wall). Accumulating evidence suggests that for optimal bone and vascular health, relatively high intakes of vitamin K are required. The synthetic short-chain vitamin K1 is commonly used in food supplements, but recently the natural long-chain menaquinone-7 (MK-7) has also become available as an over-the-counter (OTC) supplement. The purpose of this paper was to compare in healthy volunteers the absorption and efficacy of K1 and MK-7. Serum vitamin K species were used as a marker for absorption and osteocalcin carboxylation as a marker for activity. Both K1 and MK-7 were absorbed well, with peak serum concentrations at 4 hours after intake. A major difference between the 2 vitamin K species is the very long half-life time of MK-7, resulting in much more stable serum levels, and accumulation of MK-7 to higher levels (7- to 8-fold) during prolonged intake. MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 μg/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.

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 The effect of vitamin K on prothrombin time in critically ill patients: an observational registry study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sofia Dahlberg ◽  
Ulf Schött ◽  
Thomas Kander
Keyword(s):  
Propensity Score ◽  
Prothrombin Time ◽  
Critically Ill ◽  
Vitamin K ◽  
Critically Ill Patients ◽  
International Normalized Ratio ◽  
University Hospital ◽  
Red Blood Cell Transfusion ◽  
Registry Study ◽  
Exclusion Criteria

Abstract Background Previous studies have indicated that vitamin K deficiency is common in non-bleeding critically ill patients with slightly prolonged prothrombin time-international normalized ratio (PT-INR). It has never been investigated thoroughly whether the administration of vitamin K to these patients could affect their PT-INR. Therefore, the aim of this registry study was to evaluate changes in PT-INR in response to vitamin K in critically ill patients with PT-INR in the range of 1.3–1.9. Methods Patients admitted to a mixed 9-bed general intensive care unit at a University Hospital, between 2013 and 2019 (n = 4541) with a PT-INR between 1.3 and 1.9 at any time during the stay were identified. Patients who received vitamin K with appropriate sampling times for PT-INR and without exclusion criteria were matched with propensity score to patients from the same cohort who did not receive vitamin K (controls). PT-INR was measured at admission, within 12 h before vitamin K administration and 12–36 h following vitamin K administration. Exclusion criteria included pre-existing liver cirrhosis, any plasma or platelet transfusion, or > 1 unit red blood cell transfusion between PT-INR samplings. Results Propensity score matching resulted in two groups of patients with 129 patients in each group. PT-INR decreased in both groups (1.4 [1.3–1.4] in the vitamin K group and 1.4 [1.3–1.6] in the controls, p < 0.001 and p = 0.004, respectively). The decrease in PT-INR was slightly more pronounced in patients who received vitamin K (delta PT-INR − 0.10 [− 0.30 to − 0.10] in the vitamin K group and − 0.10 [− 0.20 to 0.10] in the controls, p = 0.01). Conclusion In critically ill patients with a PT-INR of 1.3–1.9, the administration of vitamin K resulted in a slightly larger decrease of PT-INR 12–36 h after administration compared to controls. Future studies should focus on identifying which patient populations may benefit most from vitamin K administration as well as whether vitamin K could be a better alternative than plasma or prothrombin complex concentrate to improve PT-INR before non-emergent invasive procedures.

scholarly journals Vitamin K-Dependent Coagulation Factors That May be Responsible for Both Bleeding and Thrombosis (FII, FVII, and FIX)

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 42S-47S ◽  
Author(s):  
Antonio Girolami ◽  
Silvia Ferrari ◽  
Elisabetta Cosi ◽  
Claudia Santarossa ◽  
Maria Luigia Randi
Keyword(s):  
Venous Thrombosis ◽  
Vitamin K ◽  
Protein C ◽  
Protein S ◽  
Coagulation Factors ◽  
Bleeding Tendency ◽  
Clotting Factors ◽  
Protein Z ◽  
Clinical Observations

Vitamin K-dependent clotting factors are commonly divided into prohemorrhagic (FII, FVII, FIX, and FX) and antithrombotic (protein C and protein S). Furthermore, another protein (protein Z) does not seem strictly correlated with blood clotting. As a consequence of this assumption, vitamin K-dependent defects were considered as hemorrhagic or thrombotic disorders. Recent clinical observations, and especially, recent advances in molecular biology investigations, have demonstrated that this was incorrect. In 2009, it was demonstrated that the mutation Arg338Leu in exon 8 of FIX was associated with the appearance of a thrombophilic state and venous thrombosis. The defect was characterized by a 10-fold increased activity in FIX activity, while FIX antigen was only slightly increased (FIX Padua). On the other hand, it was noted on clinical grounds that the thrombosis, mainly venous, was present in about 2% to 3% of patients with FVII deficiency. It was subsequently demonstrated that 2 mutations in FVII, namely, Arg304Gln and Ala294Val, were particularly affected. Both these mutations are type 2 defects, namely, they show low activity but normal or near-normal FVII antigen. More recently, in 2011-2012, it was noted that prothrombin defects due to mutations of Arg596 to Leu, Gln, or Trp in exon 15 cause the appearance of a dysprothrombinemia that shows no bleeding tendency but instead a prothrombotic state with venous thrombosis. On the contrary, no abnormality of protein C or protein S has been shown to be associated with bleeding rather than with thrombosis. These studies have considerably widened the spectrum and significance of blood coagulation studies.

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.

Age still matters: Prognosticating short- and long-term mortality for critically ill patients with pneumonia

2010 ◽  
Vol 38 (11) ◽  
pp. 2126-2132 ◽  
Author(s):  
Wendy I. Sligl ◽  
Dean T. Eurich ◽  
Thomas J. Marrie ◽  
Sumit R. Majumdar
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Short And Long Term ◽  
Long Term Mortality
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