Medscape is available in 5 Language Editions – Choose your Edition here.


Vitamin K Deficiency

  • Author: Dieu-Thu Nguyen-Khoa, MD, FACP; Chief Editor: George T Griffing, MD  more...
Updated: Dec 18, 2015


Vitamin K (VK) deficiency can occur in any age group but is encountered most often in infancy. VK, an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins, is found in green, leafy vegetables and in oils, such as soybean, cottonseed, canola, and olive oils.[1] VK is also synthesized by colonic bacteria. (See Etiology and Epidemiology below.)

The 3 main types of VK are K-1 (also known as phylloquinone or phytonadione), which is derived from plants; K-2 (menaquinone), which is produced by the intestinal flora; and K-3 (menadione), which is a synthetic, water-soluble form used for treatment.

Infants with VK deficiency are at risk for hemorrhagic disease of newborn, caused by a lack of VK reaching the fetus across the placenta, the low level of VK in breast milk, and low colonic bacterial synthesis.[2, 3, 4] (However, a large amount of VK given to a pregnant patient can lead to jaundice in a newborn.) In adults, VK deficiency is uncommon because of the intake of a wide variety of vegetables and other foods, the body’s ability to recycle VK, and adequate gut flora production of VK. (See Etiology below, Treatment, and Medication.)

Because diet is the main source of VK, an adult's daily requirement has been estimated at 100-200 mcg/day. About 80-85% of VK is absorbed mainly in the terminal ileum into the lymphatic system; therefore, bile salts and normal fat absorption, as well as normal-functioning villi of the ileum, are necessary for the effective uptake of VK. If a healthy person is subject to a complete dietary absence of VK, his/her VK reserve is adequate for 1 week. (See Etiology below.)



Vitamin K (VK) acts as a cofactor; it is needed for the conversion of 10-12 glutamic acid residue on the NH2 -terminal of precursor coagulation proteins into the action form of gamma-carboxyglutamic acid (which occurs via VK-dependent gamma-glutamyl carboxylase).[5, 6, 7] This essential reaction allows the VK-dependent proteins to bind to surface phospholipids through calcium ion channel–mediated binding, in order to start the normal antithrombotic process. The exact mechanism by which VK functions as cofactor with the carboxylase is not fully understood.

Vitamin K is required in the synthesis of four clotting factors in the liver: factors II,VII, IX, and X. It is also essential in the production of protein C and S, which are anticoagulant proteins.[8]

Bone matrix proteins, specifically osteocalcin, undergo gamma carboxylation with calcium much the way coagulation factors do; this process also requires VK.


Complications and Prognosis


The characteristics of vitamin K (VK) deficiency vary according to the age of onset. In infants, its deficiency causes hemorrhagic disease of newborn, resulting in intracranial and retroperitoneal bleeding, which can occur at 1-7 days postpartum. Late hemorrhagic disease of newborn can occur as late as 3 months postpartum. (See Presentation and Workup.)[9, 10]

Because VK is involved in gamma carboxylation of osteocalcin, which is important in bone synthesis, osteoporosis is associated with VK deficiency.[11, 12, 13] Osteocalcin is important in the remodeling and mineralization of bone.


Patients with VK deficiency have a very good prognosis if the condition is recognized early and treated appropriately. No mortalities from VK deficiency have been reported. However, severe bleeding can occur if the deficiency is left untreated. Morbidity correlates with the severity of vitamin K deficiency. (See Treatment and Medication.)



In infants, the low transmission of vitamin K (VK) across the placenta, liver prematurity with prothrombin synthesis, lack of VK in breast milk, and the sterile gut in neonates account for VK deficiency.[2, 3, 4, 14]  Neonatal diseases that cause cholestasis can result in VK deficiency.[8]  Parental refusal of VK prophylaxis at childbirth can result in bleeding sequela. [8]

In adults, the causes of VK deficiency include the following[14, 15] :

  • Chronic illness
  • Malnutrition
  • Alcoholism
  • Multiple abdominal surgeries
  • Long-term parenteral nutrition
  • Malabsorption syndromes
  • Infectious diarrhea
  • Cholestatic disease
  • Parenchymal liver disease
  • Cystic fibrosis
  • Inflammatory bowel disease
  • Drugs - Antibiotics (cephalosporin), cholestyramines, warfarin, salicylates, anticonvulsants, and certain sulfa drugs) are some of the common causes of VK deficiency
  • Massive transfusion
  • Disseminated intravascular coagulation (DIC) - Severe
  • Chronic kidney disease/hemodialysis [16]

Parenchymal liver diseases, such as cirrhosis secondary to viral hepatitis, alcohol intake, and other infiltrative diseases; hepatic malignancy; amyloidosis; Gaucher disease; alpha-1 antitrypsin deficiency, and others decrease the synthesis of VK-dependent factors. Therefore, supplementation with VK is not effective unless a patient has severe bleeding and fresh frozen plasma is administered in addition to correct the coagulopathy.

Malabsorption syndrome affects VK absorption in the ileum. Celiac sprue, tropical sprue, Crohn disease, ulcerative colitis, Ascaris infection, bacterial overgrowth, chronic pancreatitis, and short bowel syndrome resulting from multiple abdominal surgeries can result in poor absorption of VK (which can be corrected with VK supplementation).[17]

Biliary diseases, such as common duct obstruction due to stones and strictures, primary biliary cirrhosis, cholangiocarcinoma, and chronic cholestasis, cause maldigestion of fat. The decrease in fat absorption leads to a deficiency of fat-soluble vitamins, such as VK.[4] In addition, surgery and T-tube drainage of the bile duct can lead to a VK-deficient state.

Dietary deficiency occurs in people with malnutrition, alcoholics, and patients undergoing long-term parenteral nutrition without VK supplements. A large amount of vitamin E can antagonize VK and prolong the prothrombin time (PT).

Various drugs, such as cholestyramine, bind to bile acids, thus preventing fat-soluble vitamin absorption. Coumadin blocks the effect of VK epoxide reductase and VK reductase, thereby inducing an intracellular deficiency. Cefamandole, cefoperazone, salicylates, hydantoins, rifampin, isoniazid, and barbiturates are some of the common drugs that are associated with VK deficiency, but their mechanism of action in this condition is unknown.

Because two main sources of VK exist, neither dietary deficiency nor gut sterilization produces significant coagulopathy in a healthy person.



Vitamin K (VK) deficiency can occur in any age group, but it is encountered most often in infancy. In the United States, the prevalence of VK deficiency varies by geographic region.[3] In infants, VK deficiency without bleeding may occur in as many as 50% of infants younger than 5 days. The classic hemorrhagic disease occurs in 0.25-1.7% of infants. The prevalence of late hemorrhagic disease in breastfed infants is about 20 cases per 100,000 live births with no prior VK prophylaxis.

Comparing incidences of VK deficiency between different countries is difficult because countries have different criteria to acquire their national incidences. Among countries that share the same methodologies, western European countries have an incidence of late VK deficiency bleeding in infants of approximately 5 cases per 105 live births; the incidence is 11 cases per 105 live births in Japan; and the incidence is 72 cases per 105 live births in Thailand.[18]

Contributor Information and Disclosures

Dieu-Thu Nguyen-Khoa, MD, FACP Associate Clinical Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Physician Specialist, Department of Primary Care and Community Medicine, ValleyCare Olive View-UCLA Medical Center

Dieu-Thu Nguyen-Khoa, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.


Pankaj Patel, MD Fellow, Department of Gastroenterology, Winthrop University Hospital and The School of Medicine at Stony Brook University Medical Center

Pankaj Patel, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Mageda Mikhail, MD Assistant Professor, Department of Medicine, Division of Endocrinology, The School of Medicine at Stony Brook University Medical Center

Mageda Mikhail, MD is a member of the following medical societies: Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.


Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, and Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. Suttie JW. Vitamin K. Machlin L, ed. Handbook of Vitamins. New York, NY: Marcel Dekker; 1984. 147.

  2. Van Winckel M, De Bruyne R, Van De Velde S, et al. Vitamin K, an update for the paediatrician. Eur J Pediatr. 2008 Nov 4. [Medline].

  3. Shearer MJ. Vitamin K deficiency bleeding (VKDB) in early infancy. Blood Rev. 2008 Sep 18. [Medline].

  4. van Hasselt PM, de Koning TJ, Kvist N, et al. Prevention of vitamin K deficiency bleeding in breastfed infants: lessons from the Dutch and Danish biliary atresia registries. Pediatrics. 2008 Apr. 121(4):e857-63. [Medline].

  5. Beutler E, Lichtman MA, Coller BS. Disorders of the vitamin K dependent coagulation factors. Williams Hematology. 5th ed. New York, NY: McGraw-Hill; 1995. 1481-5.

  6. Furie B, Furie BC. Molecular basis of vitamin K-dependent gamma-carboxylation. Blood. 1990 May 1. 75(9):1753-62. [Medline]. [Full Text].

  7. Udall JA. Human sources and absorption of vitamin K in relation to anticoagulation stability. JAMA. 1965 Oct 11. 194(2):127-9. [Medline].

  8. Burke CW. Vitamin K deficiency bleeding: overview and considerations. J Pediatr Health Care. May-June 2013. 27:215-21. [Medline].

  9. Ozdemir MA, Karakukcu M, Per H, Unal E, Gumus H, Patiroglu T. Late-type vitamin K deficiency bleeding: experience from 120 patients. Childs Nerv Syst. 2011 Sep 18. [Medline].

  10. Takahashi D, Shirahata A, Itoh S, Takahashi Y, Nishiguchi T, Matsuda Y. Vitamin K prophylaxis and Late Vitamin K deficiency bleeding in infants: The 5th nation-wide survey in Japan. Pediatr Int. 2011 Apr 22. [Medline].

  11. Furie B. Vitamin K: metabolism and disorders. Hoffman R, Benz EJ, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000. 1958-62.

  12. Nakajima S, Iijima H, Egawa S, Shinzaki S, Kondo J, Inoue T, et al. Association of vitamin K deficiency with bone metabolism and clinical disease activity in inflammatory bowel disease. Nutrition. 2011 Oct. 27(10):1023-8. [Medline].

  13. Vermeer C, Theuwissen E. Vitamin K, osteoporosis and degenerative diseases of ageing. Menopause Int. 2011 Mar. 17(1):19-23. [Medline].

  14. Booth SL, Al Rajabi A. Determinants of vitamin K status in humans. Vitam Horm. 2008. 78:1-22. [Medline].

  15. Ansell JE, Kumar R, Deykin D. The spectrum of vitamin K deficiency. JAMA. 1977 Jul 4. 238(1):40-2. [Medline].

  16. Kristin M McCabe, Michael A. Adams, Rachel M. Holden. Vitamin K Status in Chronic Kidney Disease. Nutrition. November 2013. 5:4390-4398.

  17. Krasinski SD, Russell RM, Furie BC. The prevalence of vitamin K deficiency in chronic gastrointestinal disorders. Am J Clin Nutr. 1985 Mar. 41(3):639-43. [Medline]. [Full Text].

  18. Martin J. Shearer, Xueyan Fu, Sarah L. Booth. Vitamin K Nutrition, Metabolism, and Requirement: Current Concept and Future Research. Advances in Nutrition. 2012. 3:182-195.

  19. Lee GR, Bithell TC, Forester J. Acquired coagulation disorders. Wintrobe's Clinical Hematology. Baltimore, Md: Williams & Wilkins; 1993: 1473-80.

  20. Liebman HA, Furie BC, Tong MJ. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med. 1984 May 31. 310(22):1427-31. [Medline].

  21. Merli GJ, Fink J. Vitamin K and thrombosis. Vitam Horm. 2008. 78:265-79. [Medline].

  22. Klebanoff MA, Read JS, Mills JL, et al. The risk of childhood cancer after neonatal exposure to vitamin K. N Engl J Med. 1993 Sep 23. 329(13):905-8. [Medline]. [Full Text].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.