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Vitamin K Deficiency

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

Background

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.)

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Physiology

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.

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Complications and Prognosis

Complications

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.

Prognosis

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.)

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Etiology

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.

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Epidemiology

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]

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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

Acknowledgements

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

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