Vitamin K deficiency results
from extremely inadequate intake, fat malabsorption, or use of coumarin
anticoagulants. Deficiency is particularly common among breastfed
infants. It impairs clotting.
Diagnosis is suspected based on routine
coagulation study findings and confirmed by response to vitamin K.
Treatment consists of vitamin K given orally or, when fat malabsorption
is the cause or when risk of bleeding is high, parenterally.
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,
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
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).
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.
(See also Overview of Vitamins.)
Etiology
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, malabsorption disorders, cystic fibrosis, 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
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
-
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
-
Phytonadione
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
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.
Key Points
-
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.
Posts
0 Comments