Approach Considerations
The medical therapy for vitamin K (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.
In adults, VK-1 should be administered subcutaneously or intramuscularly. If the PT does not normalize after VK supplementation, then consideration should be made for the presence of liver disease or DIC.
If there is a high risk for hematoma formation with intramuscular or subcutaneous VK administration, then an oral form of VK can be administered in 5- to 20-mg doses, depending on the severity. The absorption with the oral form is variable because it requires bile salts in the ileum for absorption. This form is used in the setting of asymptomatic VK deficiency.
VK-3, a menadione, is a synthetic, water-soluble compound used to treat VK deficiency associated with maldigestion and malabsorption syndromes; however, it is not used in newborns due to the hemolysis observed with higher doses.
In urgent situations, 10-20 mg of injectable phytonadione (VK-1) can be dissolved in a 5% dextrose or 0.9% normal saline to be administered intravenously at a rate not to exceed 1 mg/mL to prevent a hypersensitive or anaphylactic reaction. When giving VK in the intravenous form, the patient needs to be monitored closely, because cardiopulmonary arrest and/or shock can occur in rare cases. The parenteral administration of VK-1 corrects VK deficiency in 12-24 hours.
There is currently no consensus on dosing for chronic supplementation for patients with cystic fibrosis. However, because of limited stores of vitamin K and its fast turnover in the body, daily supplementation is recommended. Dosages for all ages range from 0.3 to 1 mg/day. [18, 26]
Consultations
Consultations should be considered with a hematologist and a gastroenterologist.
A hematologist can exclude conditions that can mimic vitamin K (VK) deficiency. Bleeding time, PT/aPTT, and serum DCP level (PIVKA level) are ordered to assist the physician in diagnosing the VK deficiency. A hematologist can aid in the interpretation of laboratory results.
A gastroenterologist is consulted when the hematologic or dietary causes of VK deficiency are excluded. They can help diagnose inflammatory bowel disease, malabsorption, and parenchymal liver disease that can cause a VK-deficient state.
Diet
The main sources of VK are plants. The following are rich in vitamin K:
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Oils (eg, olive, canola, cottonseed, safflower, and soybean).
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Green, leafy vegetables and common vegetables (eg, green peas and beans, watercress, asparagus, spinach, and broccoli).
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Oats and whole wheat.
No consensus has been reached on a recommended daily allowance for VK. Current adequate intake (AI) index for VK in the United States is 90 mcg/day for women and 120 mcg/day for men. The AI for pregnant and lactating women are 75 mcg/day and 90 mcg/day, respectively. [19] AI recommendations for VK only fulfill the requirement for coagulation function.
For patients on parenteral nutrition, 150 mcg/day of phylloquinone is provided in a multivitamin preparation. Careful monitoring of the international normalized ratio (INR) is needed in patients who are on anticoagulation and receiving high supplemental dosing of VK, because this can create a warfarin-resistant state. [19]
Prevention
Vitamin K injection at birth is highly effective in preventing vitamin K deficiency bleeding in infants, and since 1961, the American Academy of Pediatrics (AAP, has recommended a prophylactic dose of intramuscular vitamin K be given up to 6 hours after birth. [10] There is no evidence of increased risk for adverse events associated with vitamin K prophylaxis. The risk of developing vitamin K deficiency bleeding is 81 times greater in infants who do not receive a vitamin K injection. [11, 27, 28]
Although a study in the early 1990s found an association between vitamin K injection and childhood cancer, these results were never replicated in subsequent studies. [29, 30] The AAP reviewed the evidence regarding vitamin K and cancer risk in 1993, and again in 2003, and reaffirmed its recommendation for intramuscular injection both times. [10] Nevertheless, in 2013 the CDC investigated a cluster of large cranial bleeds caused by vitamin K deficiency in infants who had not received prophylaxis at birth because of parental concerns of cancer risk or toxic effects of preservatives. [31] Parents of infants who opt out of the vitamin K injection report being unaware that the risk for vitamin K deficiency bleeding lasts up to 6 months. [31, 32]
Universal neonatal vitamin K prophylaxis is further by complicated by state public health laws that can be inconsistent with the AAP guidelines. According to the CDC, 20 states lack statutes related to neonatal vitamin K prophylaxis, and among the 30 states that do, there is significant variability in the framework for administration of prophylaxis. [11]
Similarly, although the World Health Organization has released recommendations for intramuscular vitamin K for newborns, there is no agreement globally of the optimal dose, route, and frequency of administration of vitamin K. Among developed countries, there is a variety of oral and intramuscular (IM) regimens of vitamin K administration at birth being utilized. [33]
