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VOLUME 5 , ISSUE 3 ( July-September, 2023 ) > List of Articles


Vitamin K and Glucose-6-phosphate Dehydrogenase Deficiency: A Perspective

Arti Pawaria, Mridul C Das, Vikrant Sood

Keywords : Glucose-6-phosphate dehydrogenase deficiency, Review, Vitamin K

Citation Information : Pawaria A, Das MC, Sood V. Vitamin K and Glucose-6-phosphate Dehydrogenase Deficiency: A Perspective. Ann Pediatr Gastroenterol Hepatol 2023; 5 (3):47-51.

DOI: 10.5005/jp-journals-11009-0133

License: CC BY-NC 4.0

Published Online: 18-10-2023

Copyright Statement:  Copyright © 2023; The Author(s).


The use of vitamin K in a patient with suspected or proven glucose-6-phosphate dehydrogenase (G6PD) deficiency is a controversial topic with divided opinions even among the subject experts. We thus aim to summarize the available literature and provide the personal viewpoint of the authors on this aspect.

  1. Beulens JW, Booth SL, van den Heuvel EG, et al. The Role of Menaquinones (Vitamin K2) in Human Health. Br J Nutr 2013;110(8):1357–1368. DOI: 10.1017/S0007114513001013
  2. McCann JC, Ames BN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr 2009;90(4):889–907. DOI: 10.3945/ajcn.2009.27930
  3. Bus K, Szterk A. Relationship between structure and biological activity of various vitamin K forms. Foods 2021;10(12):3136. DOI: 10.3390/foods10123136
  4. Vetrella M. Relationship between structure and biological activity of various vitamin K forms. Foods 2021;3136.
  5. Booth SL. Roles for vitamin K beyond coagulation. Annu Rev Nutr 2009;29:89–110. DOI: 10.1146/annurev-nutr-080508
  6. Shearer MJ, Fu X, Booth SL. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr 2012;3(2):182–195. DOI: 10.3945/an.111.001800
  7. Walther B, Karl JP, Booth SL, et al. Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr 2013;4(4):463–473. DOI: 10.3945/an.113.003855
  8. Schurgers LJ, Teunissen KJ, Hamulyák K, et al. Vitamin K–containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 2007;109(8):3279–3283. DOI: 10.1182/blood-2006-08-040709
  9. Garber AK, Binkley NC, Krueger DC, et al. Comparison of phylloquinone bioavailability from food sources or a supplement in human subjects. J Nutr 1999;129(6):1201–1203. DOI: 10.1093/jn/129.6.1201
  10. Vetrella M, Barthelmai W. Studies on drug-induced hemolysis: effects of menadione and its water soluble preparations on the glutathione peroxidase of human erythrocytes. Klin Wochenschr 1972;50(5):234–238. DOI: 10.1007/BF01486527
  11. Shukla S, Wu CP, Nandigama K, et al. The naphthoquinones, vitamin K3 and its structural analogue plumbagin, are substrates of the multidrug resistance linked ATP binding cassette drug transporter ABCG2. Mol Cancer Ther 2007;6(12 Pt 1):3279–3286. DOI: 10.1158/1535-7163.MCT-07-0564
  12. Beulens JW, Bots ML, Atsma F, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis 2009;203(2):489–493. DOI: 10.1016/j.atherosclerosis.2008.07.010
  13. Kaplan M, Hammerman C. Glucose-6-phosphate dehydrogenase deficiency: a potential source of severe neonatal hyperbilirubinaemia and kernicterus. Semin Neonatol 2002;7(2):121–128. DOI: 10.1053/siny.2002.0099
  14. Beutler E. G6PD deficiency. Blood 1994;84:3613–3636.
  15. Pradeep Kumar U, Yadav VR. Prevalence of glucose-6-phosphate dehydrogenase deficiency in India: an updated meta-analysis. Egypt J Med Hum Genet 2016:295–302. DOI: 10.1016/J.EJMHG.2016.01.004
  16. Kaplan M, Hammerman C. Glucose-6-phosphate dehydrogenase deficiency and severe neonatal hyperbilirubinemia: a complexity of interactions between genes and environment. Semin Fetal Neonatal Med 2010;15(3):148–156. DOI: 10.1016/j.siny.2009.10.007
  17. Kattamis C. Favism in breast-fed infants. Arch Dis Child 1971;46(249):741. DOI: 10.1136/adc.46.249.741
  18. Zinkham WH. Peripheral blood and bilirubin values in normal full-term primaquine-sensitive Negro infants: effect of vitamin K. Pediatrics 1963;31:983–995.
  19. Boyadjian M, Follenfant E, Chamouine A, et al. Acute hemolytic anemia caused by G6PD deficiency in children in mayotte: a frequent and severe complication. J Pediatr Hematol Oncol 2022;44(7):363–368. DOI: 10.1097/MPH.0000000000002381
  20. Kaplan M, Waisman D, Mazor D, et al. Effect of vitamin K1 on glucose-6-phosphate dehydrogenase deficient neonatal erythrocytes in vitro. Arch Dis Child Fetal Neonatal Ed 1998;79(3):F218–F220. DOI: 10.1136/fn.79.3.f218
  21. Valaes T, Karaklis A, Stravrakakis D, et al. Incidence and mechanism of neonatal jaundice related to glucose-6-phosphate dehydrogenase deficiency. Pediatr Res 1969;3(5):448–458. DOI: 10.1203/00006450-196909000-00008
  22. Meloni T, Costa S, Cutillo S. Haptoglobin, hemopexin, hemoglobin and hematocrit in newborns with erythrocyte glucose-6-phosphate dehydrogenase deficiency. Acta Haematol 1975;54(5):284–288. DOI: 10.1159/000208087
  23. Dhillon AS, Darbyshire PJ, Williams MD, et al. Massive acute haemolysis in neonates with glucose-6-phosphate dehydrogenase deficiency. Arch Dis Child Fetal Neonatal Ed 2003;88(6):F534–F536. DOI: 10.1136/fn.88.6.f534
  24. Capps FP, Gilles HM, Jolly H, et al. Glucose-6-phosphate dehydrogenase deficiency and neonatal jaundice in Nigeria: their relation to the use of prophylactic vitamin K. Lancet 1963;2(7304):379–383. DOI: 10.1016/s0140-6736(63)93059-9
  25. Zinkham WH, Childs B. Effect of vitamin K and naphthalene metabolites on glutathione metabolism of erythrocytes from normal newborns and patients with naphthalene hemolytic anemia. Am J Dis Child 1957;94:420–423.
  26. Kaplan M, Hammerman C. Severe neonatal hyperbilirubinemia. A potential complication of glucose-6-phosphate dehydrogenase deficiency. Clin Perinatol 1998;25(3):575–590, viii.
  27. Kaplan M, Beutler E, Vreman HJ, et al. Neonatal hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient heterozygotes. Pediatrics 1999;104(1 Pt 1):68–74. DOI: 10.1542/peds.104.1.68
  28. Iolascon A, Faienza MF, Perrotta S, et al. Gilbert's syndrome and jaundice in glucose-6-phosphate dehydrogenase deficient neonates. Haematologica 1999;84(2):99–102.
  29. Kaplan M, Hammerman C, Shapiro SM. Grand rounds hyperbilirubinemia following phototherapy in glucose-6-phosphate dehydrogenase-deficient neonates: not out of the woods. J Pediatr 2023;261:113452. DOI: 10.1016/j.jpeds.2023.113452
  30. Alam S, Lal BB, Sood V, et al. Pediatric acute-on-chronic liver failure in a specialized liver unit: prevalence, profile, outcome, and predictive factors. J Pediatr Gastroenterol Nutr 2016;63(4):400–405. DOI: 10.1097/MPG.0000000000001179
  31. Çetinkaya B, Tezer H, Özkaya Parlakay A, et al. Evaluation of pediatric patients with hepatitis a. J Infect Dev Ctries 2014;8(3):326–330. DOI: 10.3855/jidc.4057
  32. Ozbay Hosnut F, Ozcay F, Selda Bayrakci U, et al. Etiology of hemolysis in two patients with hepatitis A infection: glucose-6-phosphate dehydrogenase deficiency or autoimmune hemolytic anemia. Eur J Pediatr 2008;167(12):1435–1439. DOI: 10.1007/s00431-008-0694-1
  33. Singh SK, Borkar V, Srivastava A, et al. Need for recognizing atypical manifestations of childhood sporadic acute viral hepatitis warranting differences in management. Eur J Pediatr 2019;178(1):61–67. DOI: 10.1007/s00431-018-3262-3
  34. Choremis C, Kattamis CA, Kyriazakou M, et al. Viral hepatitis in G.-6-P.D. deficiency. Lancet 1966;1(7431):269–270. DOI: 10.1016/s0140-6736(66)90098-5
  35. Salen G, Goldstein F, Haurani F, et al. Acute hemolytic anemia complicating viral hepatitis in patients with glucose-6-phosphate dehydrogenase deficiency. Ann Intern Med 1966;65(6):1210–1220. DOI: 10.7326/0003-4819-65-6-1210
  36. Kattamis CA, Tjortjatou F. The hemolytic process of viral hepatitis in children with normal or deficient glucose-6-phosphate dehydrogenase activity. J Pediatr 1970;77(3):422–430. DOI: 10.1016/s0022-3476(70)80010-5.
  37. Hira I, Zoe W, Natalie D, et al. S3046 Hepatitis B causing severe hemolysis and multi-organ failure in patients with undiagnosed G6PD. Am J Gastroenterol Suppl 2022;117(10s):e1966–e1966.
  38. Kamar N, Bendall RP, Peron JM, et al. Hepatitis E virus and neurologic disorders. Emerg Infect Dis 2011;17(2):173–179. DOI: 10.3201/eid1702.100856
  39. Del Bello A, Guilbeau-Frugier C, Josse AG, et al. Successful treatment of hepatitis E virus-associated cryoglobulinemic membranoproliferative glomerulonephritis with ribavirin. Transpl Infect Dis 2015;17(2):279–283. DOI: 10.1111/tid.12353
  40. Li C, Wang HF. Hepatitis E virus-related acute liver failure associated with pure red cell aplasia. Hepatobiliary Pancreat Dis Int 2011;10(5):557–558. DOI: 10.1016/s1499-3872(11)60096-9
  41. Deng H, Xu M, Liu H, et al. Clinical analysis of the characteristics of patients diagnosed with hemolytic anemia induced by hepatitis E viral infection. iLiver 2022;1(2):117–121. DOI: 10.1016/j.iliver.2022.05.001
  42. Rodriguez Lay Lde L, Quintana A, Villalba MC, et al. Dual infection with hepatitis A and E viruses in outbreaks and in sporadic clinical cases: Cuba 1998–2003. J Med Virol 2008;80(5):798–802. DOI: 10.1002/jmv.21147
  43. Jonderko G. [Glutathione level in the blood in diffuse liver lesions]. Pol Arch Med Wewn 1961;31:317–320.
  44. Pitcher CS, Williams R. Reduced red cell survival in jaundice and its relation to abnormal glutathione metabolism. Clin Sci 1963;24:239–252.
  45. Tanyalcin T, Taskiran D, Topalak O, et al. The effects of chronic hepatitis C and B virus infections on liver reduced and oxidized glutathione concentrations. Hepatol Res 2000;18(2):104–109. DOI: 10.1016/s1386-6346(99)00088-1
  46. Crosby WH. The pathogenesis of spherocytes and leptocytes (target cells). Blood 1952;7(2):261–274.
  47. Arjun R, Kumanan T, Sujanitha V, et al. Dengue complicated by acute haemolysis, methaemoglobinemia, hepatitis and rhabdomyolysis in a patient with G6PD deficiency. Sri Lanka J Med 2019;28(2):75–80. DOI: 10.4038/sljm.v28i2.127
  48. May WL, Kyaw MP, Blacksell SD, et al. Impact of glucose-6-phosphate dehydrogenase deficiency on dengue infection in Myanmar children. PLoS One 2019;14(1):e0209204. DOI: 10.1371/journal.pone.0209204
  49. Al-Alimi AA, Ali SA, Al-Hassan FM, et al. Dengue virus type 2 (DENV2)—induced oxidative responses in monocytes from glucose-6-phosphate dehydrogenase (G6PD)—Deficient and G6PD normal subjects. PLoS Negl Trop Dis 2014;8(3):e2711. DOI: 10.1371/journal.pntd.0002711
  50. Malakah MA, Baghlaf BA, Alsulami SE. Co-occurring hemolysis and methemoglobinemia after COVID-19 infection in patient with G6PD deficiency. Cureus 2023;15(2):e35020. DOI: 10.7759/cureus.35020
  51. Lopes DV, Lazar Neto F, Marques LC, et al. Methemoglobinemia and hemolytic anemia after COVID-19 infection without identifiable eliciting drug: a case-report. ID Cases 2021;23:e01013. DOI: 10.1016/j.idcr.2020.e01013
  52. Burka ER, Weaver Z 3rd, Marks PA. Clinical spectrum of hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency. Ann Intern Med 1966;64(4):817–825. DOI: 10.7326/0003-4819-64-4-817
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