Vitamin K deficiency

Vitamin K deficiency
10.6.1 Defi ciency in adults
In adult humans, clinical vitamin K defi ciency manifests
as occult bleeding. Abnormal blood coagulation
is more likely to arise from secondary causes such
as malabsorption syndromes or biliary obstruction
than from a dietary inadequacy of vitamin K. However,
subclinical defi ciency, manifested as decreased
urinary γ-carboxyglutamic acid excretion, has been
induced in healthy adults by dietary deprivation of
the vitamin (Ferland et al., 1993).
In a placebo-controlled study involving healthy
young and elderly adults, Binkley et al. (2000) reported
that vitamin K supplementation (1000 μg of
synthetic phylloquinone per day) resulted in a 10-
fold increase in serum phylloquinone concentration.
The mean percentage undercarboxylated osteocalcin
decreased from 7.6% to 3.4% without signifi cant
differences by age or sex. The results showed that the
usual dietary practices in the population studied did
not provide adequate vitamin K for maximal osteocalcin
carboxylation. Further research is needed to
establish whether maximal osteocalcin γ-carboxylation
is important for optimum bone mass density
and whether submaximal osteocalcin γ-carboxylation
should be used as a marker of vitamin K nutritional
status.
10.6.2 Defi ciency in infants
Plasma concentrations of the Gla-containing bloodclotting
factors (factors II, VII, IX and X) in normal
newborns range between 30 and 60% of adult values
(Vermeer & Hamulyák, 1991). These relatively low
values are not due to vitamin K defi ciency as raising
cord blood levels of phylloquinone to the endogenous
maternal range by maternal oral supplementation
does not improve coagulation in the fetus or neonate
(Mandelbrot et al., 1988). Also, there is no detectable
difference in coagulation between breast-fed and formula-
fed infants in the fi rst month of life, despite the
marked differences in serum phylloquinone concentrations
(Pietersma-de Bruyn et al., 1990). The likely
explanation for the low neonatal concentrations of
vitamin K-dependent clotting factors is reduced
synthesis of their precursor proteins. In the mouse,
gestational factor IX mRNA levels are <5% of adult
levels up to 2 days before birth, when levels begin to
rise steeply, reaching 43% of adult levels at birth. This
is followed by a gradual increase until adult levels are
reached at about 24 days of age (Yao et al., 1991).
About 30% of full-term infants have low vitamin
K status as indicated by the presence of des-γ-carboxyprothrombin
(also known as PIVKA-II) in their
plasma during the fi rst week of life (Motohara et al.,
1985). Des-γ-carboxyprothrombin represents undercarboxylated
prothrombin and is a sensitive haemostatic
marker of subclinical vitamin K defi ciency. The
low vitamin K status, coupled with the low concentrations
of vitamin K-dependent clotting factor precursor
proteins, makes infants at birth and in early life
susceptible to a syndrome referred to nowadays as
vitamin K defi ciency bleeding (VKDB) of early infancy.
This disease, formerly known as haemorrhagic
disease of the newborn, has a reported incidence of
between 2 and 10 cases per 100 000 births (Shearer,
1995a). Three syndromes have been identifi ed according
to their time of presentation: early, classic and late
VKDB. Early VKDB presents within 24 hours of birth
and is commonly manifested as bleeding within the
gut and around the genitalia. Classic VKDB presents
1 to 7 days after birth and the bleeding is usually
gastrointestinal, dermal, nasal or from circumcision.
Late VKDB, which presents 2 to 12 weeks after birth,
is the most serious syndrome and is frequently associated
with some abnormality of liver function. It has
Vitamin K 269
a 50% incidence of intracranial haemorrhage, resulting
in death or severe and permanent brain damage
(Shearer, 1995b).
Owing to limited placental transfer of maternal
phylloquinone to the fetus, babies are born with low
liver reserves of vitamin K. After birth, it takes several
weeks before the liver stores of menaquinones attain
adult levels. The absence of an intestinal microfl ora
during the fi rst few days of life may be signifi cant in
this regard. The newborn is entirely dependent on
milk for its supply of vitamin K and hence any delay
in the establishment of lactation may be a risk factor
for classic VKDB. The vitamin K content of mature
human milk ranges from 0.85 to 9.2 μg L–1 with a
mean concentration of 2.5 μg L–1, but can be increased
by maternal intakes of pharmacological doses of the
vitamin. By comparison, cow’s milk contains 5 μg L–1
and infant formulas contain 50–100 μg L–1 (Institute
of Medicine, 2001). Two major risk factors for VKDB
are exclusive breast feeding and not giving vitamin K
prophylaxis at birth. Premature babies now routinely
receive intramuscular or (less effectively) oral doses of
vitamin K as a prophylactic measure against VKDB.