INTRODUCTION — Vitamins are a number of chemically unrelated families of organic substances that cannot be synthesized by humans but need to be ingested in the diet in small quantities to prevent disorders of metabolism. They are divided into water-soluble and fat-soluble vitamins (table 1). Vitamin K has a major role in coagulation pathways because it is a cofactor required for the activity of several key proteins containing carboxyglutamic acid residues. Vitamin K deficiency is rare except in neonates and patients with predisposing conditions including hepatobiliary or pancreatic disease.
Vitamin K antagonists (VKA) are a class of drugs used for therapeutic anticoagulation. The pharmacology and use of these drugs is discussed in separate topic reviews. (See "Warfarin and other VKAs: Dosing and adverse effects" and "Management of warfarin-associated bleeding or supratherapeutic INR" and "Reversal of anticoagulation in intracranial hemorrhage".)
This topic review will focus on vitamin K. Overviews of the other fat-soluble vitamins, minerals, and water-soluble vitamins are available elsewhere. (See "Overview of vitamin A" and "Overview of vitamin D" and "Overview of vitamin E" and "Overview of dietary trace elements" and "Overview of water-soluble vitamins" and "Vitamin intake and disease prevention".)
CHEMISTRY — Vitamin K and its derivatives contain a 2-methyl-1,4- naphthoquinone nucleus with a lipophilic side chain (figure 1). The structure is similar to warfarin and other coumarin-like anticoagulants, which function as vitamin K antagonists. Vitamin K1 (phylloquinone) has a phytyl side chain. Vitamin K2 (menaquinone) has several forms, each with an isoprenoid side chain, designated MK-4 (or menatetrenone) through MK-13 according to the length of the side chain. The most common form of menaquinone has four residues (MK-4).
METABOLISM — Vitamin K absorption requires intact pancreatic and biliary function and fat absorptive mechanisms. Dietary vitamin K is protein-bound and is liberated by the proteolytic action of pancreatic enzymes in the small intestine. Bile salts then solubilize vitamin K into mixed micelles for absorption into enterocytes, where it is incorporated into chylomicrons, thereby facilitating absorption into the intestinal lymphatics and portal circulation for transport to the liver [1]. In the liver it is repackaged into very low-density lipoprotein (VLDL). It circulates in small quantities bound to lipoprotein.
ACTIONS — Vitamin K has a major role in coagulation pathways because it is a cofactor required for the activity of several key proteins containing carboxyglutamic acid residues. Several other proteins within the body (eg, osteocalcin) also contain carboxyglutamate residues and depend upon vitamin K for their activity (table 2). (See "Vitamin K and the synthesis and function of gamma-carboxyglutamic acid".)
●Coagulation – Vitamin K is essential for activity of several carboxylase enzymes within hepatic cells and is therefore necessary for the activation of coagulation factors VII, IX, X, and prothrombin. These factors contain carboxyglutamic acid, which is carboxylated by gamma-glutamyl carboxylase, an endoplasmic enzyme found in mammalian cells (figure 2) [2,3]. Vitamin K is the active coenzyme in this process, providing energy for the reaction through oxidation [4]. After carboxylation, these proteins gain affinity for the negatively charged phospholipids on the surface of platelets and promote coagulation [5].
●Activation of proteins C and S – The natural anticoagulants proteins S and C also require vitamin K for their antithrombotic activity. Protein C, following its activation by thrombin, inactivates factors Va and VIIIa, thus inhibiting excess generation of thrombin (see "Protein C deficiency", section on 'Pathophysiology'). Protein S also helps prevent excessive coagulation through its action as a cofactor for activated protein C [6]. (See "Protein S deficiency".)
●Reversal of coumarin-like anticoagulants – Coumarin-like anticoagulants, which are similar in structure to vitamin K (figure 1), interrupt the vitamin K-dependent carboxylation cycle by blocking reduction of the inactive vitamin K 2,3 epoxide to the active form of the vitamin (figure 2) [7]. Vitamin K administration is one of the methods used to reverse the effects of coumarin, including for patients with anticoagulant rodenticide poisoning. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of bleeding' and "Reversal of anticoagulation in intracranial hemorrhage" and "Anticoagulant rodenticide poisoning: Management".)
●Bone formation – Vitamin K is a cofactor for some proteins involved in bone mineralization, including osteocalcin (bone gamma-carboxyglutamic acid [Gla] protein) and matrix Gla protein (see "Normal skeletal development and regulation of bone formation and resorption", section on 'Biochemistry of bone mineral matrix'). Clinical trials have examined the use of vitamin K1 (phylloquinone) or vitamin K2 for the treatment of osteoporosis, with conflicting results, which are discussed separately. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Therapies not recommended'.)
●Coronary vascular calcification – Matrix Gla protein is dependent on vitamin K-mediated carboxylation for activity. In its active form it is thought to play a role in vascular calcification. Theoretically, vitamin K deficiency leads to increased vascular calcification because of lack of matrix Gla protein activity. Vascular calcification predisposes to coronary artery disease. Few trials have assessed the role of vitamin K in coronary artery disease. Those available are not conclusive, but they suggest that further studies are warranted [8,9].
●COVID-19 – In addition to respiratory failure, thromboembolic events are frequent complications of severe COVID-19 infection. Vitamin K preferentially actives hepatic procoagulant pathways over extrahepatic anticoagulant protein S. Vitamin K also activates matrix Gla protein, which protects vascular and pulmonary endothelium. Studies demonstrate that uncarboxylated or inactive matrix Gla protein is elevated in COVID-19 patients compared with controls, suggesting that extra-hepatic vitamin K deficiency is associated with poorer outcomes in severe COVID-19 infection [10].
SOURCES — Dietary vitamin K1 (phylloquinone) is found in green vegetables like spinach and broccoli and in some oils (table 3) [7]. Phytonadione is a synthetic form of vitamin K1.
Vitamin K2 (menaquinone) is distinguished by an isoprenoid side chain. There are several forms, designated MK-4 through MK-13 according to the length of the side chain. MK-4 (also known as menatetrenone) can be produced from phylloquinone by the body and is the main storage form in animals. The other menaquinones are synthesized by microflora in the gut, providing a portion of the dietary requirement of vitamin K [7]. Dietary menaquinones are found in meat (especially liver), cheeses, fermented soybeans, and eggs. However, except for liver and some fermented soy products, the concentrations are low, so most of these foods do not provide a significant portion of dietary vitamin K. The most common forms of vitamin K2 have approximately 60 percent of the activity of vitamin K1, by weight, but the bioavailability of all forms of vitamin K varies substantially depending on other intraluminal nutrients [1,11].
REQUIREMENTS
Dietary reference intake — The dietary requirement for vitamin K, expressed as adequate intake (AI), is 90 micrograms daily in females and 120 micrograms daily in males [1]. The AI in children ranges from 2 micrograms daily in young infants to 75 micrograms daily in adolescent boys (table 4). The AI in infants assumes that infants also receive vitamin K prophylaxis at birth (see 'Prevention' below). The primary source of vitamin K in most diets is as vitamin K1 (phylloquinone) from leafy green vegetables or oils (table 3). A few foods, mainly fermented cheeses, have significant amounts of vitamin K2 (menaquinones).
Special populations — Special considerations apply to vitamin K requirements in the following populations:
Patients on parenteral nutrition — Patients on total parenteral nutrition require vitamin K supplementation. Vitamin K is included in most brands of standard multivitamin mix added to the parenteral nutrition solution. A typical daily dose of adult injectable multivitamins for parenteral nutrition includes 150 micrograms of vitamin K1 (phytonadione). For patients on warfarin, daily intake of 150 micrograms of vitamin K1 has not been associated with a requirement for excessive doses of warfarin, or subtherapeutic anticoagulation, as long as the anticoagulation regimen is appropriately monitored and doses are adjusted as needed. Nonetheless, for patients on warfarin, some providers select a brand of multivitamin mix that does not contain vitamin K (eg, MVI-12).
Patients on anticoagulant therapy — Vitamin K antagonists (VKA) are a class of anticoagulant drugs whose therapeutic action depends upon antagonism of vitamin K. The dose of the drug must be carefully balanced with vitamin K intake to achieve the desired degree of anticoagulation. In a study of healthy subjects stably anticoagulated with the VKA acenocoumarol, use of food supplements providing up to 100 micrograms/day of vitamin K1 did not significantly interfere with treatment [12]. The threshold dose of vitamin K1 causing a statistically significant lowering of the international normalized ratio (INR) in these subjects was 150 micrograms/day, an amount easily exceeded following the ingestion of one-half cup of kale (table 3). Patients taking these drugs must pay attention to their dietary vitamin K intake. Maintaining a relatively stable level of intake over time is preferred to restriction. (See "Warfarin and other VKAs: Dosing and adverse effects".)
VITAMIN K DEFICIENCY — Vitamin K deficiency in an otherwise healthy child or adult is rare. This is largely due to the wide distribution of phylloquinone in plants, menaquinone production by gut micro-flora, and because vitamin K is easily recycled within cells (figure 2). Vitamin K deficiency is common in newborn infants, prompting routine administration of vitamin K prophylaxis at birth. (See 'Vitamin K-deficient bleeding in newborns and young infants' below.)
Acquired vitamin K deficiency can occur due to drugs such as antibiotics, or other predisposing conditions as listed below. Prolonged fasting or starvation also decreases vitamin K levels. Such patients are more sensitive to treatment with coumarin-based anticoagulants [13]. (See 'Predisposing conditions' below and 'Patients on anticoagulant therapy' above.)
Predisposing conditions — Vitamin K is a fat-soluble vitamin, thus any cause of fat malabsorption may result in vitamin K deficiency. Fat malabsorption may be caused by disorders of bile or pancreatic secretion, or by extensive disease or resection of the intestinal mucosa. As examples, patients with the following conditions are at risk for fat-soluble vitamin deficiencies and usually require supplementation and monitoring, as discussed in the corresponding topic reviews:
●Cystic fibrosis. (See "Cystic fibrosis: Nutritional issues", section on 'Vitamin K'.)
●Primary biliary cholangitis. (See "Overview of the management of primary biliary cholangitis", section on 'Fat-soluble vitamins'.)
●Primary sclerosing cholangitis. (See "Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis", section on 'Steatorrhea and vitamin deficiency'.)
●Biliary atresia. (See "Biliary atresia", section on 'Fat-soluble vitamin supplements'.)
●Familial intrahepatic cholestasis and other inherited disorders associated with cholestasis. (See "Inherited disorders associated with conjugated hyperbilirubinemia".)
●Intestinal diseases associated with malabsorption, such as active celiac disease, inflammatory bowel disease, or short bowel syndrome, may be associated with vitamin K deficiency. This is particularly true if the terminal ileum is involved because this can cause maldigestion of the fat-soluble vitamins by reducing the bile salt pool. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults" and "Vitamin and mineral deficiencies in inflammatory bowel disease" and "Chronic complications of short bowel syndrome in children".)
●Liver failure – Because the vitamin K-dependent coagulation factors are synthesized in the liver, severe parenchymal liver disease also may lead to deficiencies of these factors. In patients with severe liver disease and coagulation abnormalities, measurement of factors V and VII can help to distinguish between liver parenchymal dysfunction and vitamin K malabsorption. Factor V activity does not depend on vitamin K while factor VII activity requires vitamin K as a coenzyme for carboxylation. Thus, in vitamin K malabsorption, factor V activity will be preserved while factor VII will be depressed. In liver failure, both factors V and VII activity will be impaired. (See "Hemostatic abnormalities in patients with liver disease".)
●Medications – Medications that may contribute to vitamin K deficiency include antibiotics and high doses of vitamin E:
•Antibiotics can contribute to vitamin K deficiency by affecting intestinal bacteria and also through direct effects on vitamin K activation in the liver. Most of the ingested vitamin K is absorbed in the distal small intestine. A number of microorganisms, which colonize the colon and distal ileum, synthesize absorbable vitamin K (vitamin K2, menaquinone). Many broad-spectrum antibiotics diminish this population of bacteria, limiting menaquinone production [14]. Second- and third-generation cephalosporin antibiotics are associated with hypoprothrombinemia and have a weak coumarin-like effect in patients with low vitamin K stores [15]. They cause vitamin K deficiency by inhibiting the function of vitamin K epoxide reductase enzyme in the liver, therefore impairing the recycling of vitamin K (figure 2) [15]. (See "Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects", section on 'Hematologic reactions'.)
•Very high doses of vitamin E can cause vitamin K deficiency but do not appear to affect absorption [16]. In a rat animal model, supplementation with toxic doses of vitamin A resulted in vitamin K deficiency with hypoprothrombinemia and cerebral hemorrhage [17].
Symptoms — Clinical signs and symptoms of vitamin K deficiency include easy bruisability, mucosal bleeding, splinter hemorrhages, melena, hematuria, or any other manifestations of impaired coagulation.
Laboratory evaluation
●Symptomatic patients – For patients with bleeding symptoms, the possibility of vitamin K deficiency can be evaluated by measuring prothrombin time (PT) and international normalized ratio (INR), both of which are prolonged in vitamin K deficiency. When the deficiency is mild, only the PT may be prolonged, due to a predominant effect on factor VII. In severe vitamin K deficiency, both the PT and partial thromboplastin time (PTT) may be affected. (See "Clinical use of coagulation tests", section on 'Prothrombin time (PT) and INR'.)
●Monitoring of patients with predisposing conditions – Levels of PIVKA-II (protein induced in vitamin K absence, also known as des-gamma-carboxy prothrombin) are more sensitive than PT in detecting vitamin K deficiency and may be helpful in monitoring patients with diseases predisposing to vitamin K deficiency. PIVKA-II is also elevated in the presence of vitamin K antagonists (VKA) drugs or certain tumors such as hepatocellular carcinoma. The frequency of monitoring depends upon the type of predisposing condition and the patient's history. In patients with cystic fibrosis-related liver disease, annual monitoring with PIVKA-II or PT is recommended. (See "Cystic fibrosis: Nutritional issues", section on 'Vitamin K' and "Chronic complications of short bowel syndrome in children", section on 'Common deficiencies'.)
PT and INR are also used for monitoring anticoagulant therapy with warfarin or other VKA drugs. (See 'Patients on anticoagulant therapy' above and "Warfarin and other VKAs: Dosing and adverse effects".)
Vitamin K status also can be determined indirectly by measuring vitamin K-dependent factors (ie, prothrombin, factors VII, IX, X, or protein C). In patients who are vitamin K deficient, levels of these factors often are less than 50 percent of normal. Phylloquinone levels also can be measured directly but are impractical for clinical use [18,19]. There are no established normal values for menaquinones.
Treatment of coagulopathy — For most adults with vitamin K deficiency and coagulopathy, we treat with a single 10 mg dose of oral vitamin K. In patients with vitamin K deficiency due to malabsorption or in those who cannot take oral medications, we administer the 10 mg dose of vitamin K parenterally (subcutaneously or intravenously).
However, in patients with generalized edema (anasarca), subcutaneous administration should be avoided due to unreliable absorption.
In addition, intravenous administration is preferred when trying to rapidly reverse coagulopathy (eg, in the setting of significant or potentially life-threatening bleeding or prior to an invasive procedure). When giving vitamin K intravenously, the infusion should be given slowly (ie, no faster than 1 mg/minute) to reduce the risk of anaphylaxis. (See "Hemostatic abnormalities in patients with liver disease", section on 'General approach to managing bleeding'.)
If clinical evidence of coagulopathy persists despite the administration of a single dose of vitamin K, we repeat the dose in 48 to 72 hours.
The 10 mg dose is generally more than necessary to correct the deficiency, but toxicities of vitamin K are minimal.
When vitamin K deficiency occurs in patients who are also receiving coumarin-like anticoagulants, doses of vitamin K should be minimized in order to prevent refractoriness to further anticoagulation. However, in the setting of severe coagulopathy with life-threatening bleeding, a dose reduction is not appropriate. This is discussed in detail elsewhere. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Vitamin K dose, route, formulation'.)
VITAMIN K-DEFICIENT BLEEDING IN NEWBORNS AND YOUNG INFANTS — Vitamin K deficiency is common in the newborn, and if vitamin K is not replaced, the infant is at risk for vitamin K deficiency bleeding (VKDB), previously known as hemorrhagic disease of the newborn.
Pathogenesis — Newborn infants are at risk for vitamin K deficiency because their immature liver does not efficiently utilize vitamin K. In addition, they tend to have low vitamin K stores because of the low vitamin K content of breast milk, a sterile gut, and poor placental transfer of vitamin K. In infants, the plasma concentrations of all vitamin K-dependent factors are approximately 20 percent of the adult values. Within a month after birth, the levels rise to within normal limits [20]. The risk of developing VKDB is further increased by maternal ingestion during pregnancy of warfarin or other coumarin-like anticoagulants, certain antibiotics (ie, cephalosporins), and some anticonvulsants [21].
Clinical features — VKDB is characterized by cutaneous bruising or bleeding from mucosal surfaces, the gastrointestinal tract, umbilicus or circumcision site, and/or intracranial hemorrhage (ICH).
●Early-onset VKDB develops within the first 24 hours of life and is usually associated with maternal medications that block vitamin K action (eg, anticonvulsants). It is associated with ICH in approximately 25 percent of affected infants [22].
●Classic VKDB develops between the second and seventh day of life and is largely prevented by administration of vitamin K at birth [23].
●Late-onset VKDB typically develops between three weeks and eight months of age. There is a high frequency of ICH in affected infants (eg, 50 percent in some series), and associated central nervous system symptoms such as vomiting or seizures may be the primary presenting symptoms [24].
Late-onset VKDB and associated ICH appear to be increasing in the United States, and these cases are associated with the parental refusal of vitamin K prophylaxis at birth, followed by exclusive breast feeding [21,25,26]. It also can be precipitated by fat malabsorption due to gastrointestinal, pancreatic, or hepatobiliary disease such as biliary atresia or cystic fibrosis, or by coumarin poisoning [24,27]. One study documented ICH due to VKDB in 21 Egyptian infants despite standard parenteral vitamin K prophylaxis at birth; risk factors included exclusive breast feeding, diarrhea, and antibiotic consumption [28].
Evaluation — The possibility of VKDB should be considered in an infant presenting during the first six months of life with bleeding, bruising, lethargy, or fussiness, especially if they are exclusively breastfed or did not receive vitamin K prophylaxis at birth. If there is a strong clinical suspicion of VKDB (eg, clinically apparent bleeding and known refusal of vitamin K prophylaxis), the infant should be treated immediately, even before test results are available. (See 'Treatment' below.)
Evaluation should include laboratory testing of prothrombin time (PT) and international normalized ratio (INR), both of which are prolonged in vitamin K deficiency. Infants with abnormal results or neurologic symptoms should have urgent neuroimaging to detect brain hemorrhage. A complete blood count with platelets and fibrinogen should also be performed to exclude other causes of bleeding. (See "Stroke in the newborn: Classification, manifestations, and diagnosis".)
Prevention — The American Academy of Pediatrics recommends that all newborn infants should receive vitamin K at birth as an intramuscular dose of 0.5 to 1 mg to prevent VKDB [29]. For healthy, exclusively breastfed, term infants, an alternative strategy may be oral vitamin K1 (2 mg orally with the first feed and at one, four, and eight weeks of age). However, oral supplements may be less effective in preventing late-onset VKDB in infants, and no approved oral preparation is available in the United States. (See "Overview of the routine management of the healthy newborn infant".)
Administration of a second "booster" dose of vitamin K to selected infants has been suggested as a possible approach to prevent ICH due to late-onset VKDB. Further studies are needed to determine the efficacy of this approach and selection factors.
Concerns about a possible association between vitamin K prophylaxis and childhood cancers have been carefully evaluated but not substantiated [29].
The adequate intake (AI) for vitamin K, as defined by the Food and Nutrition Board, is not increased for lactating mothers. However, one study suggests that exclusively breastfed infants often have low plasma vitamin K concentrations, and that this can be prevented by supplementation of the mother's diet with 5 mg of vitamin K1 (phylloquinone) throughout the first 12 weeks of life [30,31]. No studies have evaluated whether maternal supplementation with vitamin K prevents VKDB.
Treatment — A presumptive diagnosis of VKDB should be made in an infant presenting with bleeding or neurologic symptoms and either prolonged PT or INR, or a history of not receiving vitamin K prophylaxis at birth. Such infants should be treated immediately with parenteral vitamin K (phytonadione), 1 to 2 mg intravenously or subcutaneously. The vitamin K dose should normalize the coagulation profile within two to three hours [21,26]. For severe bleeding episodes, fresh frozen plasma or prothrombin complex concentration may be administered in addition to vitamin K. (See "Stroke in the newborn: Management and prognosis", section on 'Management of intracerebral hemorrhage'.)
VITAMIN K EXCESS — Vitamin K toxicity is very rare, and a tolerable upper limit for consumption has not been defined (table 4). Menadione, a synthetic water-soluble form of vitamin K, can cause hemolytic anemia, hyperbilirubinemia, jaundice, and kernicterus in infants [32,33]. Menadione has been used in premature or low birth weight newborns but may precipitate kernicterus in high doses [34]. However, this form of vitamin K supplementation is not available.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Vitamin deficiencies".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Warfarin (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Sources and dietary requirements – Dietary vitamin K1 (phylloquinone) is found in green vegetables like spinach and broccoli (table 3). The dietary requirement, expressed as adequate intake (AI), is 90 micrograms daily in females and 120 micrograms daily in males; the AI for children depends on age as outlined in the table (table 4). Gut micro-flora synthesizes vitamin K2 (menaquinones, including menatetrenone), which provides a portion of the dietary requirement of vitamin K. Vitamin K absorption requires intact pancreatic and biliary function and fat absorptive mechanisms. (See 'Sources' above and 'Metabolism' above and 'Requirements' above.)
●Actions
•Vitamin K is essential for activity of several carboxylase enzymes within the hepatic cells and therefore is necessary for the activation of coagulation factors VII, IX, X, and prothrombin. The natural anticoagulant proteins S and C also require vitamin K for their activity. (See 'Actions' above.)
•Coumarin-like anticoagulants are similar in structure to vitamin K (figure 1) and interrupt the vitamin K-dependent carboxylation cycle (figure 2). Vitamin K administration is one of the methods used to reverse the effects of coumarin. Patients with severely impaired liver function do not respond well to vitamin K supplementation, and coumarin-induced coagulopathy is not as easily reversed.
•Vitamin K is a cofactor for some proteins involved in bone mineralization. Clinical trials have examined the use of vitamin K1 (phylloquinone) or vitamin K2 for the treatment of osteoporosis, with conflicting results. (See 'Actions' above and "Overview of the management of osteoporosis in postmenopausal women", section on 'Therapies not recommended'.)
•Vitamin K is responsible for the carboxylation of matrix gamma-carboxyglutamic acid (Gla) protein, which is thought to limit vascular calcification and hence prevent coronary artery disease. Data are inconclusive regarding whether vitamin K deficiency plays a role in coronary artery disease. (See 'Actions' above.)
●Vitamin K deficiency
•Clinical signs and symptoms of vitamin K deficiency include easy bruisability, mucosal bleeding, splinter hemorrhages, melena, hematuria, or any other manifestations of impaired coagulation. Vitamin K deficiency in an otherwise healthy child or adult is rare. Patients at risk for vitamin K deficiency include those on long-term broad-spectrum antibiotics or those with fat malabsorption for a variety of reasons, including disorders of bile or pancreatic secretion, or extensive disease or resection of the intestinal mucosa. (See 'Symptoms' above and 'Predisposing conditions' above.)
•Vitamin K deficiency causes prolonged prothrombin time (PT) and International Normalized Ratio (INR). In more severe vitamin K deficiency, the partial thromboplastin time (PTT) also may be affected. Levels of PIVKA-II (proteins induced in vitamin K absence) are more sensitive than PT in detecting vitamin K deficiency and may be helpful in monitoring patients with diseases predisposing to vitamin K deficiency. (See 'Laboratory evaluation' above.)
●Treatment of Vitamin K deficiency in adults – For most adults with vitamin K deficiency and coagulopathy, we treat with a single 10 mg dose of oral vitamin K. Parenteral administration is preferred in patients who cannot tolerate oral medications and when trying to rapidly reverse coagulopathy. (See 'Treatment of coagulopathy' above.)
●Vitamin K deficiency in newborns – Vitamin K deficiency is common in the newborn because of immature liver function and low transfer of vitamin K through the placenta or breast milk. If vitamin K prophylaxis is not administered at birth, the infant is at risk for vitamin K deficiency bleeding (VKDB), previously known as hemorrhagic disease of the newborn. This disorder is associated with cutaneous, gastrointestinal, and intracranial bleeding in neonates, typically developing within the first week of life. A late form of VKDB can present up to eight months of age, usually in exclusively breastfed infants. To prevent VKDB, standard treatment is with vitamin K1 (0.5 to 1 mg intramuscular) administered at birth. (See 'Vitamin K-deficient bleeding in newborns and young infants' above.)
