Sakwit Anusak, Pongphitcha Pongpak, Komvilaisak Patcharee, Ochiai Masayuki, Takahashi Daijiro, Suga Shutaro, Chuansumrit Ampaiwan, Betensky Marisol, Pereira Stephen P, Afzal Amber, van Ommen C Heleen, Goldenberg Neil, Rattanasiri Sasivimol, Sirachainan Nongnuch
Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Department of Pediatrics, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Res Pract Thromb Haemost. 2025 Apr 6;9(3):102847. doi: 10.1016/j.rpth.2025.102847. eCollection 2025 Mar.
Vitamin K deficiency (VKD) in cholestatic liver disease affects up to 23% of pediatric patients. While several vitamin K (VK) prophylaxis regimens have been proposed, optimal therapeutic strategies remain undefined. The study aimed to identify the most effective VK prophylaxis for children with cholestatic liver disease. We conducted a systematic review of articles focusing on studies of children aged <18 years with cholestatic liver disease who reported outcomes of either VKD or vitamin K deficiency bleeding (VKDB) after VK prophylaxis. The articles were sourced from PubMed, Scopus, and Embase. A meta-analysis was performed to determine the prevalence of VKD and the efficacy of each prophylactic protocol in preventing VKD/VKDB. The study was registered on PROSPERO (CRD 42021270048). Of the 889 articles, 37 were selected (2 comparative studies, 6 noncomparative studies, and 29 case reports/series). The results from the comparative studies indicated a lower incidence of VKD in the parenteral than that in the oral VK. The meta-analysis of the noncomparative studies showed the prevalence of VKD in high prothrombin induced by vitamin K absence-II group was 56% (95% CI, 45%-68%; = 0.0%; = 1.0; test: χ = 1.93; = .38) and a prevalence of VKD in abnormal coagulation test was 10% (95% CI, 5%-14%; = 0%, = 1.0; test: χ = 0.82; = .66), respectively. Among the 3 administrative routes, the analysis from case reports/series showed the median onset of VKDB in cholestatic infants was the earliest in the oral (44.5 days; IQR, 13.0-240.0 days) compared with intramuscular (86.0 days; IQR, 36.0-120.0) and intravenous routes and intravenous (97.0 days; IQR, 74.0-120.0 days) VK prophylaxis. Available studies to determine the optimal route of VK administration in children with cholestatic liver disease were limited. The result from the review indicated that parenteral VK demonstrated a noticeable advantage over oral VK for VKD/VKDB prevention in cholestatic children.
胆汁淤积性肝病中的维生素K缺乏症（VKD）影响着多达23%的儿科患者。虽然已经提出了几种维生素K（VK）预防方案，但最佳治疗策略仍不明确。本研究旨在确定针对胆汁淤积性肝病患儿最有效的VK预防措施。我们对聚焦于年龄<18岁的胆汁淤积性肝病患儿的研究文章进行了系统综述，这些研究报告了VK预防后VKD或维生素K缺乏性出血（VKDB）的结果。文章来源于PubMed、Scopus和Embase。进行了一项荟萃分析，以确定VKD的患病率以及每种预防方案在预防VKD/VKDB方面的疗效。该研究已在PROSPERO（CRD 42021270048）上注册。在889篇文章中，筛选出37篇（2篇比较研究、6篇非比较研究以及29篇病例报告/系列）。比较研究的结果表明，肠外途径的VKD发生率低于口服VK途径。非比较研究的荟萃分析显示，维生素K缺乏诱导的高凝血酶原-II组中VKD的患病率为56%（95%CI，45%-68%； = 0.0%； = 1.0；检验：χ = 1.93； = 0.38），凝血试验异常组中VKD的患病率为10%（95%CI，5%-14%； = 0%， = 1.0；检验：χ = 0.82； = 0.66）。在三种给药途径中，病例报告/系列的分析显示，与肌内注射（86.0天；IQR，36.0-120.0天）和静脉途径以及静脉注射（97.0天；IQR，74.0-120.0天）的VK预防相比，胆汁淤积性婴儿中VKDB的中位发病时间在口服途径中最早（44.5天；IQR，13.0-240.0天）。现有确定胆汁淤积性肝病患儿VK最佳给药途径的研究有限。综述结果表明，在预防胆汁淤积性儿童的VKD/VKDB方面，肠外VK比口服VK具有明显优势。
