Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysis

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 chol...

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Main Authors: Anusak Sakwit, Pongpak Pongphitcha, Patcharee Komvilaisak, Masayuki Ochiai, Daijiro Takahashi, Shutaro Suga, Ampaiwan Chuansumrit, Marisol Betensky, Stephen P. Pereira, Amber Afzal, C. Heleen van Ommen, Neil Goldenberg, Sasivimol Rattanasiri, Nongnuch Sirachainan
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Research and Practice in Thrombosis and Haemostasis
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Online Access:http://www.sciencedirect.com/science/article/pii/S2475037925001712
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author Anusak Sakwit
Pongpak Pongphitcha
Patcharee Komvilaisak
Masayuki Ochiai
Daijiro Takahashi
Shutaro Suga
Ampaiwan Chuansumrit
Marisol Betensky
Stephen P. Pereira
Amber Afzal
C. Heleen van Ommen
Neil Goldenberg
Sasivimol Rattanasiri
Nongnuch Sirachainan
author_facet Anusak Sakwit
Pongpak Pongphitcha
Patcharee Komvilaisak
Masayuki Ochiai
Daijiro Takahashi
Shutaro Suga
Ampaiwan Chuansumrit
Marisol Betensky
Stephen P. Pereira
Amber Afzal
C. Heleen van Ommen
Neil Goldenberg
Sasivimol Rattanasiri
Nongnuch Sirachainan
author_sort Anusak Sakwit
collection DOAJ
description 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%; I2 = 0.0%; H2 = 1.0; Q test: χ2 = 1.93; P = .38) and a prevalence of VKD in abnormal coagulation test was 10% (95% CI, 5%-14%; I2 = 0%, H2 = 1.0; Q test: χ2 = 0.82; P = .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.
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spelling doaj-art-1b9bdf890966495d930d08985ce18d8c2025-08-20T02:05:10ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-03-019310284710.1016/j.rpth.2025.102847Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysisAnusak Sakwit0Pongpak Pongphitcha1Patcharee Komvilaisak2Masayuki Ochiai3Daijiro Takahashi4Shutaro Suga5Ampaiwan Chuansumrit6Marisol Betensky7Stephen P. Pereira8Amber Afzal9C. Heleen van Ommen10Neil Goldenberg11Sasivimol Rattanasiri12Nongnuch Sirachainan13Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Pediatrics, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandResearch Center for Environmental and Developmental Medical Sciences, Department of Pediatrics, Kyushu University, Fukuoka, JapanDivision of Neonatology, Fukuda Hospital, Kumamoto, JapanDepartment of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, JapanDepartment of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USAUCL Institute for Liver and Digestive Health, Division of Medicine, University College London, Royal Free Hospital Campus, London, United KingdomDivision of Hematology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USADepartment of Pediatric Hematology, Sophia Children’s Hospital Erasmus MC, Rotterdam, NetherlandsDepartment of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USADepartment of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Correspondence Nongnuch Sirachainan, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok 10400 Thailand.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%; I2 = 0.0%; H2 = 1.0; Q test: χ2 = 1.93; P = .38) and a prevalence of VKD in abnormal coagulation test was 10% (95% CI, 5%-14%; I2 = 0%, H2 = 1.0; Q test: χ2 = 0.82; P = .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.http://www.sciencedirect.com/science/article/pii/S2475037925001712cholestatic liver diseasechildrenvitamin Kprophylaxisbleeding
spellingShingle Anusak Sakwit
Pongpak Pongphitcha
Patcharee Komvilaisak
Masayuki Ochiai
Daijiro Takahashi
Shutaro Suga
Ampaiwan Chuansumrit
Marisol Betensky
Stephen P. Pereira
Amber Afzal
C. Heleen van Ommen
Neil Goldenberg
Sasivimol Rattanasiri
Nongnuch Sirachainan
Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysis
Research and Practice in Thrombosis and Haemostasis
cholestatic liver disease
children
vitamin K
prophylaxis
bleeding
title Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysis
title_full Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysis
title_fullStr Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysis
title_full_unstemmed Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysis
title_short Vitamin K deficiency bleeding in children with cholestatic liver disease: a systematic review and meta-analysis
title_sort vitamin k deficiency bleeding in children with cholestatic liver disease a systematic review and meta analysis
topic cholestatic liver disease
children
vitamin K
prophylaxis
bleeding
url http://www.sciencedirect.com/science/article/pii/S2475037925001712
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