Vitamin K1 Administration Increases the Level of Circulating Carboxylated Osteocalcin in Critically Ill Patients

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Abstract
Background/Objectives: Vitamin K-dependent proteins (VKDPs) all commonly possess specially modified γ-carboxyglutamic acid residues created in a vitamin K-dependent manner. Several liver-derived coagulation factors are well characterised VKDPs. However, much less is known about extrahepatic VKDPs, which are more diverse in their molecular structures and functions, and some of which have been implicated in inflammatory disorders. Vitamin K metabolism was shown to be impaired in critically ill patients, in whom systemic inflammation and sepsis are common features. Therefore, the aim of this study was to investigate the effect of vitamin K administration to these patients on their circulating levels of selected VKDPs. A particular novelty of this study was the measurement of specifically carboxylated forms of these proteins in addition to their overall levels. Methods: Blood samples were taken from 47 patients in the intensive care unit before and approximately 24 h after intravenous vitamin K1 (10 mg) administration, and proteins were analysed by specific immunoassay. Results: Vitamin K1 induced increases in plasma levels of carboxylated osteocalcin and total Gas6 (p = 0.0002 and p = 0.0032, respectively). No changes were detected in levels of carboxylated Gas6 or PIVKA-II (undercarboxylated prothrombin), although the latter positively correlated with undercarboxylated osteocalcin (r = 0.38). Conclusion: Injected vitamin K1 increases the blood levels of two distinct VKDPs in critically ill patients, both of which have been implicated in inflammation regulation, including the increased carboxylation of one of them.
Funding Information
  • Regional Research Funding Region Skåne (2024-2335)
  • Lund University ISEX-ALF (2024-2335)
  • VITAKOAG external project funding from CSL Behring, Sweden (U.S.) (2024-2335)

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