Vitamin K Effects on Gas6 and Soluble Axl Receptors in Intensive Care Patients: An Observational Screening Study

Abstract

Growth arrest-specific gene 6 protein (Gas6) is avitamin K-dependent tissue bound protein. Gas6 has been shown to promote growth and therapy resistance among different types of cancer as well as thromboembolism. The aim of this prospective screening study: ClinicalTrials.gov; Identifier: NTC3782025, was to evaluate the effects of intravenously administered vitamin K1 on Gas6 and its soluble (s)Axl receptor plasma levels in intensive care patients. Vitamin K1 was intravenously injected in non-warfarin treated patients with prolonged Owren prothrombin time international normalized ratio (PT-INR) > 1.2 and blood samples were retrieved before and 20–28 h after injection. Citrate plasma samples from 52 intensive care patients were analysed for different vitamin K dependent proteins. There was a significant, but small increase in median Gas6. Only one patient had a large increase in sAxl, but overall, no significant changes in sAxl Gas6 did not correlate to PT-INR, thrombin generation assay, coagulation factors II, VII, IX and X, but to protein S and decarboxylated matrix Gla protein (dp-ucMGP). In conclusion, there was a small increase in Gas6 over 20–28 h. The pathophysiology and clinical importance of this remains to be investigated. To verify a true vitamin K effect, improvement of Gas6 carboxylation defects needs to be studied.

Editorial for the Special Issue “Vitamin K in Chronic Disease and Human Health”

“…It should be noted that increased levels of -ucMGP have been associated with adverse outcomes in cardiovascular disease or diabetic chronic kidney disease [1,3]. On the other hand, findings from the study by Schött and coworkers indicate an association between vitamin K1 administration and increased levels of the growth arrest-specific gene 6 (Gas6) protein, a member of the extrahepatic vitamin K-dependent proteins [7]. Considering the already known pro-coagulant and anti-apoptotic properties of Gas6 linking it to thromboembolism and tumor growth, as well as the anti-cancer effects of vitamin K2, the question arises whether there are potential risks specifically associated with vitamin K1 treatment, and differences between K1 and K2 should be further clarified.…”