Editing Vitamin K (section)

== Medical uses ==
[[File:Vitamina K 20220202 122653.jpg|thumb|Injectable solutions of vitamin K]]

=== Treating vitamin deficiency in newborns ===
Vitamin K is given as an injection to newborns to prevent [[vitamin K deficiency bleeding]].<ref name=Mihatsch2016 /> The blood clotting factors of newborn babies are roughly 30–60% that of adult values; this appears to be a consequence of poor transfer of the vitamin across the placenta, and thus low fetal plasma vitamin K.<ref name=Mihatsch2016 /> Occurrence of vitamin K deficiency bleeding in the first week of the infant's life is estimated at between 1 in 60 and 1 in 250.<ref>{{Cite web |author-link=Centers for Disease Control and Prevention |date=July 24, 2023 |title=What is Vitamin K Deficiency Bleeding? |url=https://www.cdc.gov/ncbddd/vitamink/facts.html |access-date=April 18, 2024}}</ref> 

[[Human milk]] contains 0.85–9.2&nbsp;μg/L (median 2.5&nbsp;μg/L) of vitamin K<sub>1</sub>, while infant formula is formulated in range of 24–175&nbsp;μg/L.<ref name=Mihatsch2016 /> Late onset bleeding, with onset 2 to 12 weeks after birth, can be a consequence of exclusive breastfeeding, especially if there was no preventive treatment.<ref name=Mihatsch2016 /> Late onset prevalence reported at 35 cases per 100,000 live births in infants who had not received prophylaxis at or shortly after birth.<ref>{{cite journal |vauthors=Sankar MJ, Chandrasekaran A, Kumar P, Thukral A, Agarwal R, Paul VK |title=Vitamin K prophylaxis for prevention of vitamin K deficiency bleeding: a systematic review |journal=J Perinatol |volume=36 |pages=S29–35 |date=May 2016 |issue=Suppl 1 |pmid=27109090 |pmc=4862383 |doi=10.1038/jp.2016.30 }}</ref> Vitamin K deficiency bleeding occurs more frequently in the Asian population compared to the Caucasian population.<ref name=Mihatsch2016 />

Bleeding in infants due to vitamin K deficiency can be severe, leading to hospitalization, [[brain damage]], and death. Intramuscular injection, typically given shortly after birth, is more effective in preventing vitamin K deficiency bleeding than oral administration, which calls for weekly dosing up to three months of age.<ref name=Mihatsch2016>{{cite journal|vauthors=Mihatsch WA, Braegger C, Bronsky J, Campoy C, Domellöf M, Fewtrell M, Mis NF, Hojsak I, Hulst J, Indrio F, Lapillonne A, Mlgaard C, Embleton N, van Goudoever J|date=July 2016|title=Prevention of Vitamin K Deficiency Bleeding in Newborn Infants: A Position Paper by the ESPGHAN Committee on Nutrition|journal=Journal of Pediatric Gastroenterology and Nutrition|volume=63|issue=1|pages=123–129|doi=10.1097/MPG.0000000000001232|pmid=27050049|s2cid=4499477| url=https://www.zora.uzh.ch/id/eprint/134095/1/MihatschWA_2016.pdf}}</ref>

===Managing warfarin therapy===

[[Warfarin]] is an [[anticoagulant]] drug. It functions by inhibiting an enzyme that is responsible for recycling vitamin K to a functional state. As a consequence, proteins that should be modified by vitamin K are not, including proteins essential to blood clotting, and are thus not functional.<ref name="Whitlon" /> The purpose of the drug is to reduce risk of inappropriate blood clotting, which can have serious, potentially fatal consequences.<ref name=Higdon /> The proper anticoagulant action of warfarin is a function of vitamin K intake and drug dose. Due to differing absorption of the drug and amounts of vitamin K in the diet, dosing must be monitored and customized for each patient.<ref name=Gong2011>{{cite journal | vauthors = Gong IY, Schwarz UI, Crown N, Dresser GK, Lazo-Langner A, Zou G, Roden DM, Stein CM, Rodger M, Wells PS, Kim RB, Tirona RG | title = Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation | journal = PLOS ONE| volume = 6 | issue = 11 | pages = e27808 | date = November 2011 | pmid = 22114699 | pmc = 3218053 | doi = 10.1371/journal.pone.0027808 | bibcode = 2011PLoSO...627808G | doi-access = free }}</ref> Some foods are so high in vitamin K<sub>1</sub> that medical advice is to avoid those (examples: collard greens, spinach, turnip greens) entirely, and for foods with a modestly high vitamin content, keep consumption as consistent as possible, so that the combination of vitamin intake and warfarin keep the anti-clotting activity in the therapeutic range.<ref name="auto1" />

Vitamin K is a treatment for bleeding events caused by overdose of the drug.<ref name=Tomaselli2017 /> The vitamin can be administered by mouth, [[Intravenous therapy|intravenously]] or [[Subcutaneous tissue|subcutaneously]].<ref name=Tomaselli2017>{{cite journal | vauthors = Tomaselli GF, Mahaffey KW, Cuker A, Dobesh PP, Doherty JU, Eikelboom JW, Florido R, Hucker W, Mehran R, Messé SR, Pollack CV, Rodriguez F, Sarode R, Siegal D, Wiggins BS | title = 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways | journal = Journal of the American College of Cardiology | volume = 70 | issue = 24 | pages = 3042–3067 | date = December 2017 | pmid = 29203195 | doi = 10.1016/j.jacc.2017.09.1085 | doi-access = free }}</ref> Oral vitamin K is used in situations when a person's [[International normalised ratio|International normalized ratio]] is greater than 10 but there is no active bleeding.<ref name="auto1">{{cite web|title=Important Information to Know When You Are Taking: Warfarin (Coumadin) and Vitamin K |url=http://www.cc.nih.gov/ccc/patient_education/drug_nutrient/coumadin1.pdf|publisher=[[National Institute of Health]] Clinical Center Drug-Nutrient Interaction Task Force|access-date=17 April 2015|archive-url=https://web.archive.org/web/20190405123407/https://www.cc.nih.gov/ccc/patient_education/drug_nutrient/coumadin1.pdf|archive-date=5 April 2019|url-status=dead}}</ref><ref>{{cite journal |vauthors=Wigle P, Hein B, Bernheisel CR |title=Anticoagulation: Updated Guidelines for Outpatient Management |journal=Am Fam Physician |volume=100 |issue=7 |pages=426–434 |date=October 2019 |pmid=31573167 }}</ref> The newer anticoagulants [[apixaban]], [[dabigatran]] and [[rivaroxaban]] are not vitamin K antagonists.<ref>{{cite journal |vauthors=Pengo V, Crippa L, Falanga A, Finazzi G, Marongiu F, Palareti G, Poli D, Testa S, Tiraferri E, Tosetto A, Tripodi A, Manotti C|title=Questions and answers on the use of dabigatran and perspectives on the use of other new oral anticoagulants in patients with atrial fibrillation. A consensus document of the Italian Federation of Thrombosis Centers (FCSA) |journal=Thromb. Haemost. |volume=106 |issue=5 |pages=868–876 |date=November 2011 |pmid=21946939 |doi=10.1160/TH11-05-0358 |s2cid=43611422 }}</ref>

===Treating rodenticide poisoning===
[[Coumarin]] is used in the pharmaceutical industry as a precursor reagent in the synthesis of a number of synthetic anticoagulant pharmaceuticals.<ref name="pubchem19">{{cite web |url=https://pubchem.ncbi.nlm.nih.gov/compound/323 |title=Coumarin |date=4 April 2019 |publisher=PubChem, National Library of Medicine, US National Institutes of Health |access-date=13 April 2019}}</ref> One subset, [[4-hydroxycoumarins]], act as [[vitamin K antagonist]]s. They block the regeneration and recycling of vitamin K. Some of the 4-hydroxycoumarin anticoagulant class of chemicals are designed to have high potency and long residence times in the body, and these are used specifically as second generation [[rodenticide]]s ("rat poison"). Death occurs after a period of several days to two weeks, usually from internal hemorrhaging.<ref name=pubchem19/> For humans, and for animals that have consumed either the rodenticide or rats poisoned by the rodenticide, treatment is prolonged administration of large amounts of vitamin K.<ref name=Bateman2016>{{cite journal |vauthors=Bateman DN, Page CB |title=Antidotes to coumarins, isoniazid, methotrexate and thyroxine, toxins that work via metabolic processes |journal=Br J Clin Pharmacol |volume=81 |issue=3 |pages=437–445 |date=March 2016 |pmid=26255881 |pmc=4767197 |doi=10.1111/bcp.12736 }}</ref><ref>{{cite web | url = http://emedicine.medscape.com/article/818130-clinical#showall | title = Rodenticide Toxicity Treatment & Management | vauthors = Lung D | veditors = Tarabar A | work = Medscape | publisher = WebMD | date = Dec 2015 }}</ref> This dosing must sometimes be continued for up to nine months in cases of poisoning by "[[superwarfarin]]" rodenticides such as [[brodifacoum]]. Oral vitamin K<sub>1</sub> is preferred over other vitamin K<sub>1</sub> routes of administration because it has fewer side effects.<ref>{{cite book|title=Recognition and Management of Pesticide Poisonings: 6th Edition|last1=Routt Reigart|first1=J.|last2=Roberts|first2=James|year=2013|url=http://npic.orst.edu/RMPP/rmpp_ch18.pdf|pages=175}}</ref>

=== Methods of assessment ===
An increase in [[prothrombin time]], a coagulation assay, has been used as an indicator of vitamin K status, but it lacks sufficient sensitivity and specificity for this application.<ref name=Card2020>{{cite journal |vauthors=Card DJ, Gorska R, Harrington DJ |title=Laboratory assessment of vitamin K status |journal=J. Clin. Pathol. |volume=73 |issue=2 |pages=70–75 |date=February 2020 |pmid=31862867 |doi=10.1136/jclinpath-2019-205997 |s2cid=209435449 }}</ref> Serum phylloquinone is the most commonly used marker of vitamin K status. Concentrations <0.15&nbsp;μg/L are indicative of deficiency. Disadvantages include exclusion of the other vitamin K vitamers and interference from recent dietary intake.<ref name=Card2020 /> Vitamin K is required for the gamma-carboxylation of specific glutamic acid residues within the Gla domain of the 17 vitamin K–dependent proteins. Thus, a rise in uncarboxylated versions of these proteins is an indirect but sensitive and specific marker for vitamin K deficiency. If uncarboxylated prothrombin is being measured, this "Protein induced by Vitamin K Absence/antagonism (PIVKA-II)" is elevated in vitamin K deficiency. 

The test is used to assess risk of vitamin K–deficient bleeding in newborn infants.<ref name=Card2020 /> [[Osteocalcin]] is involved in calcification of bone tissue. The ratio of uncarboxylated osteocalcin to carboxylated osteocalcin increases with vitamin K deficiency. Vitamin K2 has been shown to lower this ratio and improve [[lumbar]] vertebrae [[bone mineral density]].<ref name="Su2019">{{cite journal |vauthors=Su S, He N, Men P, Song C, Zhai S |title=The efficacy and safety of menatetrenone in the management of osteoporosis: a systematic review and meta-analysis of randomized controlled trials |journal=Osteoporos Int |volume=30 |issue=6 |pages=1175–1186 |date=June 2019 |pmid=30734066 |doi=10.1007/s00198-019-04853-7 |s2cid=59616051 }}</ref> Matrix Gla protein must undergo vitamin K dependent phosphorylation and carboxylation. Elevated plasma concentration of dephosphorylated, uncarboxylated MGP is indicative of vitamin K deficiency.<ref name=Chen2019>{{cite journal |vauthors=Chen HG, Sheng LT, Zhang YB, Cao AL, Lai YW, Kunutsor SK, Jiang L, Pan A |title=Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis |journal=Eur J Nutr |volume=58 |issue=6 |pages=2191–2205 |date=September 2019 |pmid=31119401 |doi=10.1007/s00394-019-01998-3 |s2cid=162181757 |url=https://research-information.bris.ac.uk/en/publications/association-of-vitamin-k-with-cardiovascular-events-and-allcause-mortality(f531b038-58a2-4eed-946d-17f01e79a2f7).html|hdl=1983/f531b038-58a2-4eed-946d-17f01e79a2f7 |hdl-access=free }}</ref>

=== Side effects ===
No known toxicity is associated with high oral doses of the vitamin K<sub>1</sub> or vitamin K<sub>2</sub> forms of vitamin K, so regulatory agencies from US, Japan and European Union concur that no [[Tolerable upper intake level#Current recommendations|tolerable upper intake level]]s needs to be set.<ref name="DRItext" /><ref name=JapanDRI /><ref name=EFSA /> However, vitamin K<sub>1</sub> has been associated with severe adverse reactions such as [[bronchospasm]] and [[cardiac arrest]] when given intravenously. The reaction is described as a nonimmune-mediated [[Anaphylaxis|anaphylactoid reaction]], with incidence of 3 per 10,000 treatments. The majority of reactions occurred when polyoxyethylated [[castor oil]] was used as the solubilizing agent.<ref>{{cite journal | vauthors = Britt RB, Brown JN | title = Characterizing the Severe Reactions of Parenteral Vitamin K<sub>1</sub> | journal = Clinical and Applied Thrombosis/Hemostasis | volume = 24 | issue = 1 | pages = 5–12 | date = January 2018 | pmid = 28301903 | doi = 10.1177/1076029616674825 | pmc = 6714635 }}</ref>