Vitamin K deficiency decreases levels of prothrombin and other vitamin K–dependent coagulation factors, causing defective coagulation and, potentially, bleeding.
Worldwide, vitamin K deficiency causes infant morbidity and mortality.
Vitamin K deficiency causes hemorrhagic disease of the newborn Blood loss Anemia is a reduction in red cell mass or hemoglobin and is usually defined as hemoglobin or hematocrit > 2 standard deviations below the mean for age. Some authorities also consider a relative... read more , which usually occurs 1 to 7 days postpartum. In affected neonates, birth trauma can cause intracranial hemorrhage. A late form of this disease can occur in infants about 2 to 12 weeks old, typically in infants who are breastfed and are not given vitamin K supplements. If the mother has taken phenytoin antiseizure drugs, coumarin anticoagulants, or cephalosporin antibiotics, the risk of hemorrhagic disease is increased.
In healthy adults, dietary vitamin K deficiency is uncommon because vitamin K is widely distributed in green vegetables and the bacteria of the normal gut synthesize menaquinones.
Physiology of Vitamin K Deficiency
Vitamin K1 (phylloquinone) is dietary vitamin K. Sources include green leafy vegetables (especially collards, spinach, and salad greens), soy beans, and vegetable oils. Dietary fat enhances its absorption. Infant formulas contain supplemental vitamin K. After the neonatal period, bacteria in the gastrointestinal tract synthesize vitamin K, which is absorbed and used by the body.
Vitamin K2 refers to a group of compounds (menaquinones) synthesized by bacteria in the intestinal tract; the amount synthesized does not satisfy the vitamin K requirement.
Vitamin K controls the formation of coagulation factors II (prothrombin), VII, IX, and X in the liver (see table Sources, Functions, and Effects of Vitamins Sources, Functions, and Effects of Vitamins Vitamins may be Fat soluble (vitamins A, D, E, and K) Water soluble (B vitamins and vitamin C) The B vitamins include biotin, folate, niacin, pantothenic acid, riboflavin (B2), thiamin (B1)... read more ). Other coagulation factors dependent on vitamin K are protein C, protein S, and protein Z; proteins C and S are anticoagulants. Metabolic pathways conserve vitamin K. Once vitamin K has participated in formation of coagulation factors, the reaction product, vitamin K epoxide, is enzymatically converted to the active form, vitamin K hydroquinone.
The actions of vitamin K–dependent proteins require calcium. The vitamin K–dependent proteins, osteocalcin and matrix gamma-carboxy-glutamyl (Gla) protein, may have important roles in bone and other tissues. Forms of vitamin K are common therapy for osteoporosis in Japan and other countries.
Etiology of Vitamin K Deficiency
Neonates are prone to vitamin K deficiency because of the following:
The placenta transmits lipids and vitamin K relatively poorly.
The neonatal liver is immature with respect to prothrombin synthesis.
Breast milk is low in vitamin K, containing about 2.5 mcg/L (cow’s milk contains 5000 mcg/L).
The neonatal gut is sterile during the first few days of life.
In adults, vitamin K deficiency can result from
Fat malabsorption (eg, due to biliary obstruction Choledocholithiasis and Cholangitis Choledocholithiasis is the presence of stones in bile ducts; the stones can form in the gallbladder or in the ducts themselves. These stones cause biliary colic, biliary obstruction, gallstone... read more , malabsorption disorders Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more , cystic fibrosis Cystic Fibrosis Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more , or resection of the small intestine)
Use of coumarin anticoagulants
Coumarin anticoagulants interfere with the synthesis of vitamin–K dependent coagulation proteins (factors II, VII, IX, and X) in the liver.
Certain antibiotics (particularly some cephalosporins and other broad-spectrum antibiotics), salicylates, megadoses of vitamin E, and hepatic insufficiency increase risk of bleeding in patients with vitamin K deficiency.
Inadequate intake of vitamin K is unlikely to cause symptoms.
Symptoms and Signs of Vitamin K Deficiency
Bleeding is the usual manifestation. Easy bruisability and mucosal bleeding (especially epistaxis, gastrointestinal [GI] hemorrhage, menorrhagia, and hematuria) can occur. Blood may ooze from puncture sites or incisions.
Hemorrhagic disease of the newborn and late hemorrhagic disease in infants may cause cutaneous, GI, intrathoracic, or, in the worst cases, intracranial bleeding. If obstructive jaundice develops, bleeding—if it occurs—usually begins after the 4th or 5th day. It may begin as a slow ooze from a surgical incision, the gums, the nose, or GI mucosa, or it may begin as massive bleeding into the GI tract.
Diagnosis of Vitamin K Deficiency
Usually prolonged prothrombin time (PT) or elevated international normalized ratio (INR) that decreases after phytonadione
Vitamin K deficiency or antagonism (due to coumarin anticoagulants) is suspected when abnormal bleeding occurs in a patient at risk. Blood coagulation studies can preliminarily confirm the diagnosis. PT is prolonged and INR is elevated, but partial thromboplastin time (PTT), thrombin time, platelet count, bleeding time, and levels of fibrinogen, fibrin-split products, and D-dimer are normal.
If phytonadione (United States Pharmacopeia generic name for vitamin K1) 1 mg IV significantly decreases PT within 2 to 6 hours, a liver disorder is not the likely cause, and the diagnosis of vitamin K deficiency is confirmed.
Some centers can detect vitamin K deficiency more directly by measuring the serum vitamin level. The serum level of vitamin K1 ranges from 0.2 to 1.0 ng/mL in healthy people consuming adequate quantities of vitamin K1 (50 to 150 mcg a day). Knowing vitamin K intake can help interpret serum levels; recent intake affects levels in serum but not in tissues.
More sensitive indicators of vitamin K status, such as PIVKA (protein induced in vitamin K absence or antagonism) and undercarboxylated osteocalcin, are under study.
Treatment of Vitamin K Deficiency
Whenever possible, phytonadione should be given orally or subcutaneously. The usual adult dose is 1 to 20 mg. (Rarely, even when phytonadione is correctly diluted and given slowly, IV replacement can result in anaphylaxis or anaphylactoid reactions.) International normalized ratio (INR) usually decreases within 6 to 12 hours. The dose may be repeated in 6 to 8 hours if INR has not decreased satisfactorily.
Phytonadione 1 to 10 mg orally is indicated for nonemergency correction of a prolonged INR in patients taking anticoagulants. Correction usually occurs within 6 to 8 hours. When only partial correction of INR is desirable (eg, when INR should remain slightly elevated because of a prosthetic heart valve), lower doses (eg, 1 to 2.5 mg) of phytonadione can be given.
In infants, bleeding due to vitamin K deficiency can be corrected by giving phytonadione 1 mg subcutaneously or IM once. The dose is repeated if INR remains elevated. Higher doses may be necessary if the mother has been taking oral anticoagulants.
Prevention of Vitamin K Deficiency
Phytonadione 0.5 to 1 mg IM (or 0.3 mg/kg for preterm infants) is recommended for all neonates within 6 hours of birth to reduce the incidence of intracranial hemorrhage due to birth trauma and of classic hemorrhagic disease of the newborn (risk of increased bleeding 1 to 7 days after birth). It is also used prophylactically before surgery.
Some clinicians recommend that pregnant women taking antiseizure drugs receive phytonadione 10 mg orally once a day for the 1 month or 20 mg orally once a day for the 2 weeks before delivery. The low vitamin K1 content in breast milk can be increased by increasing maternal dietary intake of phylloquinone to 5 mg/day.
Vitamin K deficiency causes infant morbidity and mortality worldwide.
The deficiency causes bleeding (eg, easy bruisability, mucosal bleeding).
Suspect the deficiency in at-risk patients with abnormal or excessive bleeding.
Measure PT or INR before and after giving phytonadione; a decrease in prolonged PT or an elevated INR after phytonadione confirms the diagnosis.
Treat with oral or subcutaneous phytonadione.