Influence of Warfarin Therapy on Prothrombin Production and Its Posttranslational Modifications. (28th June 2020)

• Record Type: Journal Article
• Authors: Kondo, Akira; Kondo, Hirokazu; Nakagawa, Yoshihisa; Ito, Hiroyuki; Shimomura, Daiki; Hatanaka, Noriko; Yamamoto, Yoshikazu; Nakatani, Misato; Iwai-Kanai, Eri; Matsuo, Shuji
• Is Part Of: Journal of applied laboratory medicine. Volume 5:Number 6(2020)
• Page Start: 1216
• Page End: 1227
• Publication Date: 2020-06-28
• Subjects: Warfarin -- Prothrombin -- PIVKA-II -- N-glycan; Clinical chemistry -- Periodicals; Diagnosis, Laboratory -- Periodicals; 616.0756
• DOI: 10.1093/jalm/jfaa069
• Languages: English
• ISSNs: 2576-9456

Abstract

Abstract: Background: Protein induced by vitamin K absence-II (PIVKA-II) is produced by the liver during hepatoma and upon warfarin administration. Those patients have disturbed protein synthesis and glycosylation in the liver. This decreases the number of γ-carboxyglutamyl (Gla) residues on prothrombin, converting prothrombin into PIVKA-II. The mechanism of this conversion, however, is not clearly understood. Methods: Prothrombin was isolated from healthy and warfarin-treated individuals whose liver function of protein production was quantitatively normal. Glycan structures in the purified prothrombin containing PIVKA-II were qualitatively analyzed by high performance liquid chromatography after labeling the glycan with fluorophore 2-aminobenzamide. Results: The concentration of PIVKA-II was significantly higher in the warfarin-treated individuals than in the healthy individuals ( P < 0.001). Although protein production in the liver was normal in both groups, the concentration of prothrombin was lower in the warfarin-treated individuals than in the healthy individuals ( P < 0.001). The main glycan was A2 in the healthy and warfarin-treated individuals (86.6 ± 4.4% and 85.6 ± 3.4%, respectively). Eight types of glycan were characterized in both groups, although generation of PIVKA-II in the warfarin-treated individuals did not lead to variation in glycosylation of prothrombin. Conclusions: Warfarin therapy leads to lower amounts of prothrombin and Gla residues within prothrombin without exerting qualitative and quantitative change in glycan profile and protein synthetic function in the liver.