Abstract
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.
Highlights
Coagulation abnormalities frequently occur in critically ill patients and affect mortality [1,2]
In the present study, we demonstrated that vitamin K1 administration corrected coagulation in patients with increased Owren prothrombin times (PTs) and may affect the production and carboxylation of vitamin K-dependent proteins (VKDPs), exhibiting the potential for other positive effects
This study did not aim to study long-term effects of vitamin K1 supplementation and further studies are needed to investigate this. This is an explorative hypothesis-generating study in an area where there is a great paucity of knowledge, it is, to the best of our knowledge, the first study to evaluate the effect of intravenous vitamin K1 on routine coagulation status, coagulation factor activity, thrombin generation assay (TGA) and rotational thromboelastometry (ROTEM) analyses in critically ill patients with increased PT
Summary
Coagulation abnormalities frequently occur in critically ill patients and affect mortality [1,2]. To the best of our knowledge, there have not been any thorough investigations with regard to vitamin K1 administration in non-bleeding adult critically ill patients and its effects on vitamin K-dependent proteins (VKDPs) (Factor [F] II, FVII, FIX, FX, protein C and protein S), thrombin generation assay (TGA) and rotational thromboelastometry (ROTEM). In addition to strengthening the coagulation system, vitamin K has been suggested to have beneficial pleiotropic effects that extend beyond activation of coagulation factors [8]. These effects are thought to be mediated through several extrahepatic vitamin K-dependent proteins, with potential involvement in protection against cardiovascular [9], neurodegenerative [10] and metabolic diseases as well as cancer [8,11]
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