{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T16:43:16Z","timestamp":1793896996265,"version":"4.8.0"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Vitamin K is a lipid-soluble vitamin that is normally maintained within appropriate levels by means of dietary intake and bacterial production in the intestinal microflora. It holds a central role in coagulation homeostasis, and thus its depletion leads to hypocoagulation and haemorrhagic diathesis. The association of antibiotic therapy and vitamin E supplementation with vitamin K deficiency was previously described in animal experiments, clinical studies, and case reports. Broad-spectrum antibiotic therapy potentially leads to intestinal microflora dysbiosis and restriction of vitamin K-producing bacterial populations, resulting in decreased vitamin K levels, whereas antibiotics of the cephalosporin class with 1-N-methyl-5-thiotetrazole (NMTT) or 2-methyl-1,3,4-thiadiazole (MTD) side groups inhibit vitamin K function. Vitamin E supplementation interferes with both the bioavailability and function of vitamin K, yet its mechanisms are not fully understood. We present the case of a 45-year-old male patient, with a history of epilepsy and schizophrenia, catatonically incapacitated and immobilised, who was hospitalised in our centre for the investigation and management of aspiration pneumonia. He demonstrated a progressively worsening prolongation of international normalised ratio (INR), which was attributed to both broad-spectrum antibiotic therapy and vitamin E supplementation and was reversed upon administration of vitamin K. We highlight the need for close monitoring of coagulation parameters in patients receiving broad-spectrum antibiotic therapy, especially those with underlying malnutritive or malabsorptive conditions, and we further recommend the avoidance of NMTT- or MTD-containing antibiotics or vitamin E supplementation, unless absolutely necessary, in those patients.<\/jats:p>","DOI":"10.3390\/jpm13091349","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T11:31:18Z","timestamp":1693481478000},"page":"1349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Association of Broad-Spectrum Antibiotic Therapy and Vitamin E Supplementation with Vitamin K Deficiency-Induced Coagulopathy: A Case Report and Narrative Review of the Literature"],"prefix":"10.3390","volume":"13","author":[{"given":"Andreas M.","family":"Matthaiou","sequence":"first","affiliation":[{"name":"5th Department of Respiratory Medicine, Sotiria Thoracic Diseases General Hospital of Athens, 11527 Athens, Greece"},{"name":"Laboratory of Molecular and Cellular Pneumonology, Medical School, University of Crete, 71003 Heraklion, Greece"},{"name":"Respiratory Physiology Laboratory, Medical School, University of Cyprus, 2029 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Tomos","sequence":"additional","affiliation":[{"name":"5th Department of Respiratory Medicine, Sotiria Thoracic Diseases General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Chaniotaki","sequence":"additional","affiliation":[{"name":"Department of Laboratory Haematology, Georgios Gennimatas General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Liakopoulos","sequence":"additional","affiliation":[{"name":"Department of Laboratory Haematology, Georgios Gennimatas General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Sakellaropoulou","sequence":"additional","affiliation":[{"name":"5th Department of Respiratory Medicine, Sotiria Thoracic Diseases General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3129-1512","authenticated-orcid":false,"given":"Sofia","family":"Koukidou","sequence":"additional","affiliation":[{"name":"5th Department of Respiratory Medicine, Sotiria Thoracic Diseases General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredana-Mariana","family":"Gheorghe","sequence":"additional","affiliation":[{"name":"Department of Laboratory Haematology, Georgios Gennimatas General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanos","family":"Eskioglou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Haematology, Georgios Gennimatas General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliki","family":"Paspalli","sequence":"additional","affiliation":[{"name":"5th Department of Respiratory Medicine, Sotiria Thoracic Diseases General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Hillas","sequence":"additional","affiliation":[{"name":"5th Department of Respiratory Medicine, Sotiria Thoracic Diseases General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Dimakou","sequence":"additional","affiliation":[{"name":"5th Department of Respiratory Medicine, Sotiria Thoracic Diseases General Hospital of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1093\/ajcn\/35.5.1112","article-title":"Deficiencies of essential and conditionally essential nutrients","volume":"35","author":"Chipponi","year":"1982","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_2","unstructured":"Pazirandeh, S., Burns, D.L., and Post, T.W. (2023). Overview of Vitamin K, UpToDate Inc.. Available online: https:\/\/www.uptodate.com\/contents\/overview-of-vitamin-k."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s13668-022-00438-9","article-title":"Dysbiosis in Patients with Chronic Kidney Disease: Let. Us Talk. About Vitamin K","volume":"11","author":"Kemp","year":"2022","journal-title":"Curr. Nutr. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev.nutr.25.050304.092713","article-title":"The vitamin K-dependent carboxylase","volume":"25","author":"Berkner","year":"2005","journal-title":"Annu. Rev. Nutr."},{"key":"ref_5","unstructured":"Furie, B., Bouchard, B.A., and Post, T.W. (2023). Vitamin K and the Synthesis and Function of Gamma-Carboxyglutamic Acid, UpToDate Inc.. Available online: https:\/\/www.uptodate.com\/contents\/vitamin-k-and-the-synthesis-and-function-of-gamma-carboxyglutamic-acid."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/00001721-200201000-00007","article-title":"Vitamin K deficiency and D-dimer levels in the intensive care unit: A prospective cohort study","volume":"13","author":"Crowther","year":"2002","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_7","first-page":"36","article-title":"A study of vitamin K status in children on prolonged antibiotic therapy","volume":"40","author":"Bhat","year":"2003","journal-title":"Indian J. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1001\/archinte.1957.00260120130015","article-title":"Vitamin K deficiency associated with prolonged antibiotic administration","volume":"100","author":"Haden","year":"1957","journal-title":"AMA Arch. Intern. Med."},{"key":"ref_9","first-page":"880","article-title":"Unexpected vitamin K deficiency in hospitalized patients","volume":"109","author":"Pineo","year":"1973","journal-title":"Can. Med. Assoc. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Itagaki, H., and Hagino, T. (2019). Vitamin K deficiency-induced hemorrhagic shock after thoracentesis: A case report. BMC Gastroenterol., 19.","DOI":"10.1186\/s12876-019-0978-0"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s41038-019-0150-7","article-title":"Hypocoagulation induced by broad-spectrum antibiotics in extensive burn patients","volume":"7","author":"Liu","year":"2019","journal-title":"Burn. Trauma"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.psym.2011.01.026","article-title":"Case reports vitamin K deficiency due to prolongation of antibiotic treatment and decrease in food intake in a catatonia patient","volume":"52","author":"Nomoto","year":"2011","journal-title":"Psychosomatics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1080\/19490976.2019.1710092","article-title":"Helicobacter pylori antibiotic eradication coupled with a chemically defined diet in INS-GAS mice triggers dysbiosis and vitamin K deficiency resulting in gastric hemorrhage","volume":"11","author":"Quinn","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.1073\/pnas.81.9.2893","article-title":"Mechanism of the inhibition of the \u03b3-carboxylation of glutamic acid by N-methylthiotetrazole-containing antibiotics","volume":"81","author":"Lipsky","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/j.1552-4604.1988.tb03106.x","article-title":"Mechanism of cephalosporin-induced hypoprothrombinemia: Relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status","volume":"28","author":"Shearer","year":"1988","journal-title":"J. Clin. Pharmacol."},{"key":"ref_16","first-page":"245","article-title":"Antibiotic-induced vitamin K deficiency and the role of the presence of intestinal flora","volume":"60","author":"Shirakawa","year":"1990","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2131\/jts.14.165","article-title":"Vitamin K-reversible hypoprothrombinemia in rats: Comparison of hypoprothrombinemic changes in various strains of rats caused by vitamin K deficiency and antibiotic treatment","volume":"14","author":"Matsuura","year":"1989","journal-title":"J. Toxicol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1016\/0006-2952(89)90556-X","article-title":"Depression of liver microsomal vitamin K epoxide reductase activity associated with antibiotic-induced coagulopathy","volume":"38","author":"Matsubara","year":"1989","journal-title":"Biochem. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s12098-014-1584-3","article-title":"Role of prophylactic vitamin K in preventing antibiotic induced hypoprothrombinemia","volume":"82","author":"Aziz","year":"2015","journal-title":"Indian J. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s13312-019-1569-4","article-title":"Prophylactic vitamin K administration in neonates on prolonged antibiotic therapy: A randomized controlled trial","volume":"56","author":"Sethi","year":"2019","journal-title":"Indian J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1111\/apa.16011","article-title":"Intracranial haemorrhage associated with vitamin K deficiency in Egyptian infants","volume":"110","author":"Elalfy","year":"2021","journal-title":"Acta Paediatr. Int. J. Paediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0021-9258(19)51301-1","article-title":"Some biological effects produced by \u03b1-tocopherol quinone","volume":"159","author":"Woolley","year":"1945","journal-title":"J. Biol. Chem."},{"key":"ref_23","first-page":"242","article-title":"Interaction of vitamins E and K: Effect of high dietary vitamin E on phylloquinone activity in chicks","volume":"67","author":"Frank","year":"1997","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1093\/ajcn\/34.9.1701","article-title":"Effect of vitamin E on prothrombin levels in warfarin-induced vitamin K deficiency","volume":"34","author":"Corrigan","year":"1981","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1749-6632.1982.tb31275.x","article-title":"The effect of vitamin E on warfarin-induced vitamin K deficiency","volume":"393","author":"Corrigan","year":"1982","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"(1983). Megavitamin E supplementation and vitamin K-dependent carboxylation. Nutr. Rev., 41, 268\u2013270.","DOI":"10.1111\/j.1753-4887.1983.tb07197.x"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"(1982). Vitamin K, vitamin E and the coumarin drugs. Nutr. Rev., 40, 180\u2013182.","DOI":"10.1111\/j.1753-4887.1982.tb05302.x"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13256-023-03827-y","article-title":"Vitamin E-induced coagulopathy in a young patient: A case report","volume":"17","author":"Abrol","year":"2023","journal-title":"J. Med. Case Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1111\/j.1753-4887.2008.00123.x","article-title":"Vitamin E and K interactions\u2014A 50-year-old problem","volume":"66","author":"Traber","year":"2008","journal-title":"Nutr. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1743-7075-3-29","article-title":"Extrahepatic tissue concentrations of vitamin K are lower in rats fed a high vitamin E diet","volume":"3","author":"Tovar","year":"2006","journal-title":"Nutr. Metab."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/9\/1349\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:43:39Z","timestamp":1760129019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/13\/9\/1349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,31]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["jpm13091349"],"URL":"https:\/\/doi.org\/10.3390\/jpm13091349","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,31]]}}}