Vitamin K Deficiency

Updated: Sep 27, 2017
  • Author: Dieu-Thu Nguyen-Khoa, MD, FACP; Chief Editor: George T Griffing, MD  more...
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Practice Essentials

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.)

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. Vitamin K deficiency bleeding (VKDB) in infants is classified according to the time of presentation: early (<24 hours after birth), classic (first week after birth), and late (between 1 week and 6 months after birth). 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. [3, 5, 6, 7] (See Etiology, Treatment, and Medication.)

Bleeding is the major symptom, especially in response to minor or trivial trauma. On physical examination, ecchymosis, petechiae, hematomas, and oozing of blood at surgical or puncture sites are observed.

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.)

Measurements of serum prothrombin time (PT) tend to be elevated, and activated partial thromboplastin time (aPTT) is usually normal. [8]  Both PT and aPTT can be elevated in more severe deficiency states. The most sensitive marker that is elevated in VK deficiency states is des-gamma-carboxy prothrombin (DCP), also known as protein induced by vitamin K absence/antagonist-II (PIVKA-II). [9]  PIVA-II levels reflect the functional marker of coagulation.

The medical therapy for VK deficiency depends on the severity of the associated bleeding and the underlying disease state. The most effective approach to correcting the deficiency also depends on the nature of the bleeding and the risk of inducing a local hematoma at the VK injection site. In life-threatening bleeds, fresh frozen plasma should be administered prior to VK. [10]  There is no evidence of increased risk for adverse events associated with vitamin K prophylaxis. The risk of developing VK deficiency bleeding is 81 times greater in infants who do not receive a vitamin K injection. [11]



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). [12, 13, 14] 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 4 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. [5]

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



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, 15]  Neonatal diseases that cause cholestasis can result in VK deficiency. [5]  Parental refusal of VK prophylaxis at childbirth can result in bleeding sequela. [5]

In adults, the causes of VK deficiency include the following [15, 16] :

  • 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 [17]

The synthesis of VK-dependent factors are decreased by parenchymal liver diseases, such as cirrhosis secondary to viral hepatitis, alcohol intake, and other infiltrative diseases; hepatic malignancy; amyloidosis; Gaucher disease; and alpha-1 antitrypsin deficiency. Therefore, supplementation with VK is not effective unless a patient has severe bleeding and fresh frozen plasma is administered in addition to correcting 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). [8]

Cystic fibrosis patients who have pancreatic insufficiency, excessive or chronic antibiotic usage, or short bowel due to intestinal resection are at increased risk for vitamin K deficiency due to malabsorption. [18]

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. Warfarin 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 2 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. [19]



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. The risk of developing vitamin K deficiency bleeding is 81 times greater in infants who do not receive a  prophylactic vitamin K injection. [11]

In 50% of patients with late vitamin K deficiency bleeding (VKDB), the bleeding location involves an intracranial hemorrhage, which is associated with high mortality and morbidity.