Vitamin K Biochemistry and Pharmacokinetics: The Basis of Late Vitamin K Deficiency Intracranial Bleeding in Early Infancy

Abstract Vitamin K is a fat-soluble vitamin essential for the activation of vitamin K-dependent proteins involved in coagulation and other physiological processes. Neonates are particularly vulnerable to vitamin K deficiency due to limited placental transfer, low hepatic stores, immature liver function, and insufficient dietary intake, especially in exclusively breastfed infants. This review summarizes the biochemistry and pharmacokinetics of vitamin K, focusing on their role in the pathogenesis of late vitamin K deficiency bleeding (VKDB), including intracranial hemorrhage in early infancy. The limitations of conventional coagulation tests are discussed, highlighting the importance of functional biomarkers such as PIVKA-II (Proteins Induced by Vitamin K Absence or Antagonist-II) for the early detection of subclinical deficiency. Despite effective prophylaxis at birth, late VKDB cases still occur, likely due to declining vitamin K levels over time and nutritional factors. These findings underscore the need for prolonged vitamin K supplementation following adequate prophylaxis at birth, particularly to protect high-risk newborns from late VKDB. Strategies may include vitamin K-containing multivitamin supplementation in preterm infants, as well as daily oral vitamin K supplementation (150 µg/day) in exclusively breastfed infants, in order to ensure adequate vitamin K status during early infancy.