Nutristasis Unit, Viapath, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Nutristasis Unit, Viapath, Guy's and St. Thomas' NHS Foundation Trust, London, UK
J Clin Pathol. 2020 Feb;73(2):70-75. doi: 10.1136/jclinpath-2019-205997. Epub 2019 Dec 20.
Vitamin K is required for the ɣ-carboxylation of specific glutamic acid residues within the Gla domain of the 17 vitamin K-dependent proteins (VKDPs). The timely detection and correction of vitamin K deficiency can protect against bleeding. Vitamin K also plays a role in bone metabolism and vascular calcification. Patients at increased risk of vitamin K deficiency include those with a restricted diet or malnutrition, lipid malabsorption, cancer, renal disease, neonates and the elderly. Coagulation assays such as the prothrombin time have been used erroneously as indicators of vitamin K status, lacking sufficient sensitivity and specificity for this application. The measurement of phylloquinone (K) in serum is the most commonly used marker of vitamin K status and reflects abundance of the vitamin. Concentrations <0.15 µg/L are indicative of deficiency. Disadvantages of this approach include exclusion of the other vitamin K homologues and interference from recent dietary intake. The cellular utilisation of vitamin K is determined through measurement of the prevalence of undercarboxylated VKDPs. Most commonly, undercarboxylated prothrombin (Protein Induced by Vitamin K Absence/antagonism, PIVKA-II) is used (reference range 17.4-50.9 mAU/mL (Abbott Architect), providing a retrospective indicator of hepatic vitamin K status. Current clinical applications of PIVKA-II include supporting the diagnosis of vitamin K deficiency bleeding of the newborn, monitoring exposure to vitamin K antagonists, and when used in combination with α-fetoprotein, as a diagnostic marker of hepatocellular carcinoma. Using K and PIVKA-II in tandem is an approach that can be used successfully for many patient cohorts, providing insight into both abundance and utilisation of the vitamin.
维生素 K 是 17 种维生素 K 依赖性蛋白(VKDP)中 Gla 结构域内特定谷氨酸残基进行 γ-羧化所必需的。及时发现和纠正维生素 K 缺乏可预防出血。维生素 K 在骨骼代谢和血管钙化中也发挥作用。有发生维生素 K 缺乏风险的患者包括饮食受限或营养不良、脂类吸收不良、癌症、肾病、新生儿和老年人。凝血酶原时间等凝血检测曾被错误地用作维生素 K 状态的指标,缺乏足够的敏感性和特异性。血清叶绿醌(K)的测量是最常用的维生素 K 状态标志物,反映了维生素的丰度。浓度<0.15μg/L 提示缺乏。这种方法的缺点包括排除其他维生素 K 同系物和近期饮食摄入的干扰。维生素 K 的细胞利用情况通过测量未羧化 VKDP 的流行率来确定。最常用的是未羧化凝血酶原(维生素 K 缺乏/拮抗剂诱导蛋白,PIVKA-II)(参考范围 17.4-50.9 mAU/mL(Abbott Architect),提供肝维生素 K 状态的回顾性指标。目前 PIVKA-II 的临床应用包括支持新生儿维生素 K 缺乏性出血的诊断、监测维生素 K 拮抗剂的暴露情况,以及与甲胎蛋白联合使用时,作为肝细胞癌的诊断标志物。将 K 和 PIVKA-II 联合使用是一种可成功用于许多患者群体的方法,可以深入了解维生素的丰度和利用情况。