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Vitamin K Deficiency

Updated : June 5, 2024





Background

Vitamin K deficiency is characterized by inadequate levels of vitamin K in the body. Vitamin K is a fat-soluble vitamin that plays a crucial role in blood clotting and bone health. It exists in two primary forms: vitamin K1 (phylloquinone), which is derived from plant sources, and vitamin K2 (menaquinone), which is produced by bacteria in the gut and can also be found in certain animal-based foods.

Vitamin K is essential for producing several clotting factors in the liver, which are necessary for the normal clotting of blood. Without sufficient vitamin K levels, blood clotting may be impaired, leading to an increased risk of excessive bleeding or prolonged bleeding times. In addition to its role in blood clotting, vitamin K also helps regulate calcium metabolism in the body, contributing to bone health. It activates proteins that assist in calcium binding, promoting the mineralization of bones and teeth.

Vitamin K deficiency can occur for various reasons, including inadequate dietary intake, malabsorption issues, certain medical conditions, or prolonged use of medications that interfere with vitamin K metabolism. Newborn babies are particularly susceptible to vitamin K deficiency because they are born with low levels of the vitamin and have limited stores.

Epidemiology

Before the routine administration of vitamin K injections to newborns, the incidence of vitamin K deficiency bleeding (VKDB) in this population was estimated to be around 0.25% to 1.7%. However, with the widespread practice of vitamin K prophylaxis at birth, the incidence of VKDB has been significantly reduced.

The prevalence of vitamin K deficiency can be higher in certain patient groups with underlying medical conditions or taking specific medications. For example, individuals with malabsorption conditions, such as cystic fibrosis or inflammatory bowel disease, may have an increased risk. Similarly, patients on long-term antibiotic therapy, anticoagulant medications, or anticonvulsants may be more prone to developing deficiencies.

Anatomy

Pathophysiology

Vitamin K is essential for the synthesis of several coagulation factors, including factors II (prothrombin), VII, IX, and X, as well as proteins C, S, and Z. These factors are produced in their inactive forms and require vitamin K-dependent carboxylation to become biologically active. Carboxylation adds a carbon dioxide molecule to specific glutamic acid residues, allowing the proteins to bind calcium ions and participate in clot formation.

In vitamin K deficiency, insufficient activation of these clotting factors impairs the normal clotting process, leading to an increased risk of bleeding and abnormal bleeding times. Vitamin K also plays a role in bone health by modulating calcium metabolism. It activates a protein called osteocalcin, which is involved in the mineralization of bones and teeth.

Osteocalcin requires carboxylation by vitamin K to bind calcium effectively. In vitamin K deficiency, reduced carboxylation of osteocalcin results in impaired bone mineralization, potentially leading to decreased bone density and an increased risk of osteoporosis. It is also involved in synthesizing anticoagulant proteins, including protein C and protein S. These proteins regulate blood clotting by inhibiting excessive clot formation.

Vitamin K deficiency can impair the synthesis of these proteins, leading to an imbalance in the body’s clotting system and an increased propensity for clot formation. In addition to its well-known role in the liver, emerging research suggests that vitamin K has extrahepatic effects on various tissues and organs. Vitamin K-dependent proteins, such as matrix Gla protein (MGP), have been found to prevent calcification in blood vessels and soft tissues. Vitamin K deficiency may contribute to arterial calcification and increase the risk of cardiovascular diseases.

Etiology

The etiology of vitamin K deficiency can be attributed to various factors that disrupt the normal intake, absorption, metabolism, or utilization of vitamin K. Here are the primary etiological factors:

Inadequate Dietary Intake: A diet lacking in vitamin K-rich foods is one of the primary causes of deficiency. Vitamin K1 is found in green leafy vegetables (such as spinach, kale, and broccoli), vegetable oils (such as soybean and canola oil), and certain fruits. Vitamin K2 is present in fermented foods, organ meats, and some animal products. Individuals with poor nutrition, restricted diets, or limited access to nutrient-rich foods are at higher risk.

Malabsorption Disorders: Conditions that affect the absorption of fat-soluble vitamins can lead to vitamin K deficiency. Examples include cystic fibrosis, celiac disease, inflammatory bowel disease, chronic pancreatitis, and bile duct obstruction. These conditions impair the absorption of dietary fats and fat-soluble vitamins, including vitamin K.

Antibiotics and Medications: Prolonged use of certain medications can interfere with vitamin K metabolism or reduce its absorption. Broad-spectrum antibiotics can disrupt the gut microbiota, which are responsible for synthesizing vitamin K2. Anticoagulant medications, such as warfarin, inhibit the action of vitamin K-dependent clotting factors. Other medications, including anticonvulsants (e.g., phenytoin) and some cholesterol-lowering drugs, may also interfere with vitamin K metabolism.

Liver Disease: The liver is responsible for the production and activation of vitamin K-dependent clotting factors. Liver diseases, such as cirrhosis or liver failure, can impair the synthesis and release of these factors, leading to vitamin K deficiency.

Disruption of Gut Microbiota: Alterations in the gut microbiota composition, such as those caused by antibiotic use, gastrointestinal infections, or certain medical conditions, can affect the production of vitamin K2 by gut bacteria. Changes in the gut flora can lead to reduced vitamin K synthesis and contribute to deficiency.

Other Factors: Certain genetic conditions or inherited disorders, such as vitamin K epoxide reductase deficiency (VKORC1 gene mutation) or mutations in the gamma-glutamyl carboxylase gene, can result in impaired vitamin K metabolism and utilization.

Genetics

Prognostic Factors

Clinical History

Clinical History

The patient may report a history of bleeding symptoms or abnormal bleeding tendencies. These symptoms can include easy bruising, and the patient may notice an increased tendency to develop bruises even with minor injuries or trauma. Bleeding from cuts, wounds, or surgical procedures may take longer than usual to stop.

Frequent or recurrent nosebleeds may be reported. The patient may experience bleeding gums while brushing teeth or during dental procedures. Women may report abnormally heavy or prolonged menstrual periods. The patient may recall excessive or abnormal bleeding in the past, such as excessive bleeding after dental extractions or oral surgeries.

Persistent bleeding after minor cuts or injuries. Gastrointestinal bleeding may present as blood in the stool or black, tarry stools, or blood in the urine may be reported. A family history of bleeding disorders or excessive bleeding tendencies may be explored, as some inherited conditions can affect vitamin K metabolism or clotting factors.

Physical Examination

Physical Examination

Physical findings on examination in a patient with vitamin K deficiency can vary depending on the severity and duration of the deficiency. The patient may have widespread or excessive bruising on the skin. These bruises may occur spontaneously or with minimal trauma. They can vary in size, color (ranging from red to purple to yellowish green), and distribution.

Tiny, pinpoint-sized red or purple spots (petechiae) may be visible on the skin or mucous membranes, such as the conjunctiva (the white part of the eyes). Petechiae result from the leakage of blood from capillaries into the surrounding tissues. Bleeding gums may be observed during oral examination or dental procedures.

The gums may appear swollen, inflamed and bleed easily, even with gentle brushing or flossing. In severe cases of vitamin K deficiency, the patient may exhibit signs of anemia, including fatigue, weakness, shortness of breath, and palpitations.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The primary intervention for vitamin K deficiency is vitamin K supplementation. This can be achieved through oral or parenteral (intravenous or intramuscular) administration, depending on the severity and urgency of the deficiency. Oral vitamin K1 (phytonadione) supplements are typically prescribed for mild to moderate deficiencies.

The dosage and duration of treatment will depend on the individual’s needs and the healthcare provider’s recommendation. Parenteral vitamin K is preferred in severe cases or situations requiring rapid deficiency correction. This route ensures faster absorption and effectiveness. It is commonly used in newborns with vitamin K deficiency bleeding or individuals with malabsorption issues.

If the deficiency is related to medications that interfere with vitamin K metabolism, such as anticoagulants or anticonvulsants, the healthcare provider may consider adjusting the dosage or prescribing alternative medications if feasible and safe. Regular follow-up visits and monitoring of clotting parameters (e.g., PT, INR) are important to assess the response to treatment and ensure adequate correction of the deficiency.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

menadione 

The recommended dose is 0.03 mcg/kg/day intravenously



menadione 

Take 10 mg orally four times a day



 

menadione 

The recommended dose is 1 to 5 mcg/kg/day intravenously



 

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References

Vitamin K Deficiency

Updated : June 5, 2024




Vitamin K deficiency is characterized by inadequate levels of vitamin K in the body. Vitamin K is a fat-soluble vitamin that plays a crucial role in blood clotting and bone health. It exists in two primary forms: vitamin K1 (phylloquinone), which is derived from plant sources, and vitamin K2 (menaquinone), which is produced by bacteria in the gut and can also be found in certain animal-based foods.

Vitamin K is essential for producing several clotting factors in the liver, which are necessary for the normal clotting of blood. Without sufficient vitamin K levels, blood clotting may be impaired, leading to an increased risk of excessive bleeding or prolonged bleeding times. In addition to its role in blood clotting, vitamin K also helps regulate calcium metabolism in the body, contributing to bone health. It activates proteins that assist in calcium binding, promoting the mineralization of bones and teeth.

Vitamin K deficiency can occur for various reasons, including inadequate dietary intake, malabsorption issues, certain medical conditions, or prolonged use of medications that interfere with vitamin K metabolism. Newborn babies are particularly susceptible to vitamin K deficiency because they are born with low levels of the vitamin and have limited stores.

Before the routine administration of vitamin K injections to newborns, the incidence of vitamin K deficiency bleeding (VKDB) in this population was estimated to be around 0.25% to 1.7%. However, with the widespread practice of vitamin K prophylaxis at birth, the incidence of VKDB has been significantly reduced.

The prevalence of vitamin K deficiency can be higher in certain patient groups with underlying medical conditions or taking specific medications. For example, individuals with malabsorption conditions, such as cystic fibrosis or inflammatory bowel disease, may have an increased risk. Similarly, patients on long-term antibiotic therapy, anticoagulant medications, or anticonvulsants may be more prone to developing deficiencies.

Vitamin K is essential for the synthesis of several coagulation factors, including factors II (prothrombin), VII, IX, and X, as well as proteins C, S, and Z. These factors are produced in their inactive forms and require vitamin K-dependent carboxylation to become biologically active. Carboxylation adds a carbon dioxide molecule to specific glutamic acid residues, allowing the proteins to bind calcium ions and participate in clot formation.

In vitamin K deficiency, insufficient activation of these clotting factors impairs the normal clotting process, leading to an increased risk of bleeding and abnormal bleeding times. Vitamin K also plays a role in bone health by modulating calcium metabolism. It activates a protein called osteocalcin, which is involved in the mineralization of bones and teeth.

Osteocalcin requires carboxylation by vitamin K to bind calcium effectively. In vitamin K deficiency, reduced carboxylation of osteocalcin results in impaired bone mineralization, potentially leading to decreased bone density and an increased risk of osteoporosis. It is also involved in synthesizing anticoagulant proteins, including protein C and protein S. These proteins regulate blood clotting by inhibiting excessive clot formation.

Vitamin K deficiency can impair the synthesis of these proteins, leading to an imbalance in the body’s clotting system and an increased propensity for clot formation. In addition to its well-known role in the liver, emerging research suggests that vitamin K has extrahepatic effects on various tissues and organs. Vitamin K-dependent proteins, such as matrix Gla protein (MGP), have been found to prevent calcification in blood vessels and soft tissues. Vitamin K deficiency may contribute to arterial calcification and increase the risk of cardiovascular diseases.

The etiology of vitamin K deficiency can be attributed to various factors that disrupt the normal intake, absorption, metabolism, or utilization of vitamin K. Here are the primary etiological factors:

Inadequate Dietary Intake: A diet lacking in vitamin K-rich foods is one of the primary causes of deficiency. Vitamin K1 is found in green leafy vegetables (such as spinach, kale, and broccoli), vegetable oils (such as soybean and canola oil), and certain fruits. Vitamin K2 is present in fermented foods, organ meats, and some animal products. Individuals with poor nutrition, restricted diets, or limited access to nutrient-rich foods are at higher risk.

Malabsorption Disorders: Conditions that affect the absorption of fat-soluble vitamins can lead to vitamin K deficiency. Examples include cystic fibrosis, celiac disease, inflammatory bowel disease, chronic pancreatitis, and bile duct obstruction. These conditions impair the absorption of dietary fats and fat-soluble vitamins, including vitamin K.

Antibiotics and Medications: Prolonged use of certain medications can interfere with vitamin K metabolism or reduce its absorption. Broad-spectrum antibiotics can disrupt the gut microbiota, which are responsible for synthesizing vitamin K2. Anticoagulant medications, such as warfarin, inhibit the action of vitamin K-dependent clotting factors. Other medications, including anticonvulsants (e.g., phenytoin) and some cholesterol-lowering drugs, may also interfere with vitamin K metabolism.

Liver Disease: The liver is responsible for the production and activation of vitamin K-dependent clotting factors. Liver diseases, such as cirrhosis or liver failure, can impair the synthesis and release of these factors, leading to vitamin K deficiency.

Disruption of Gut Microbiota: Alterations in the gut microbiota composition, such as those caused by antibiotic use, gastrointestinal infections, or certain medical conditions, can affect the production of vitamin K2 by gut bacteria. Changes in the gut flora can lead to reduced vitamin K synthesis and contribute to deficiency.

Other Factors: Certain genetic conditions or inherited disorders, such as vitamin K epoxide reductase deficiency (VKORC1 gene mutation) or mutations in the gamma-glutamyl carboxylase gene, can result in impaired vitamin K metabolism and utilization.

Clinical History

The patient may report a history of bleeding symptoms or abnormal bleeding tendencies. These symptoms can include easy bruising, and the patient may notice an increased tendency to develop bruises even with minor injuries or trauma. Bleeding from cuts, wounds, or surgical procedures may take longer than usual to stop.

Frequent or recurrent nosebleeds may be reported. The patient may experience bleeding gums while brushing teeth or during dental procedures. Women may report abnormally heavy or prolonged menstrual periods. The patient may recall excessive or abnormal bleeding in the past, such as excessive bleeding after dental extractions or oral surgeries.

Persistent bleeding after minor cuts or injuries. Gastrointestinal bleeding may present as blood in the stool or black, tarry stools, or blood in the urine may be reported. A family history of bleeding disorders or excessive bleeding tendencies may be explored, as some inherited conditions can affect vitamin K metabolism or clotting factors.

Physical Examination

Physical findings on examination in a patient with vitamin K deficiency can vary depending on the severity and duration of the deficiency. The patient may have widespread or excessive bruising on the skin. These bruises may occur spontaneously or with minimal trauma. They can vary in size, color (ranging from red to purple to yellowish green), and distribution.

Tiny, pinpoint-sized red or purple spots (petechiae) may be visible on the skin or mucous membranes, such as the conjunctiva (the white part of the eyes). Petechiae result from the leakage of blood from capillaries into the surrounding tissues. Bleeding gums may be observed during oral examination or dental procedures.

The gums may appear swollen, inflamed and bleed easily, even with gentle brushing or flossing. In severe cases of vitamin K deficiency, the patient may exhibit signs of anemia, including fatigue, weakness, shortness of breath, and palpitations.

The primary intervention for vitamin K deficiency is vitamin K supplementation. This can be achieved through oral or parenteral (intravenous or intramuscular) administration, depending on the severity and urgency of the deficiency. Oral vitamin K1 (phytonadione) supplements are typically prescribed for mild to moderate deficiencies.

The dosage and duration of treatment will depend on the individual’s needs and the healthcare provider’s recommendation. Parenteral vitamin K is preferred in severe cases or situations requiring rapid deficiency correction. This route ensures faster absorption and effectiveness. It is commonly used in newborns with vitamin K deficiency bleeding or individuals with malabsorption issues.

If the deficiency is related to medications that interfere with vitamin K metabolism, such as anticoagulants or anticonvulsants, the healthcare provider may consider adjusting the dosage or prescribing alternative medications if feasible and safe. Regular follow-up visits and monitoring of clotting parameters (e.g., PT, INR) are important to assess the response to treatment and ensure adequate correction of the deficiency.

menadione 

The recommended dose is 0.03 mcg/kg/day intravenously



menadione 

Take 10 mg orally four times a day



menadione 

The recommended dose is 1 to 5 mcg/kg/day intravenously