2. Signs of Vitamin K deficiency
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
2
3. Coagulopathy
The predominant clinical sign of
vitamin K deficiency is hemorrhage,
which can lead to a fatal anemia.
The blood shows prolonged clotting
time and hypoprothrombinemia.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
3
4. Coagulopathy
• Because a 50% loss of plasma
prothrombin level is required to
affect prothrombin time,
prolongation of the prothrombin
time is a useful biomarker for
advanced subclinical vitamin K
deficiency.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
4
5. Coagulopathy
• Patients with
dysprothrombinemia (factor
VII, congenital deficiency of
protein C) show
coagulopathies.
• None respond to high doses
of vitamin K!
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
5
6. Undercarboxylated proteins
A more sensitive indicator
of low vitamin K status is
the presence in plasma of
under-γ-carboxylated
vitamin K-dependent
proteins.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
6
7. Undercarboxylated proteins
Protein Induced by
Vitamin K Absence (PIVKA)
Under-γ-Carboxylated
Osteocalcin
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
7
8. Risk factors for vitamin K
deficiency
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8
9. Lipid malabsorption
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9
10. Anticoagulant therapy
• Warfarin, other 4-hydroxycoumarin
anticoagulants and large doses of salicylates
inhibit the redox-cycling of the vitamin.
• High doses of vitamin K are generally
effective in normalizing clotting mechanisms.
• In medical management of thrombotic
disorders, over-anticoagulation with warfarin
is common.
• This is reversed by warfarin dose reduction
coupled with treatment with phylloquinone.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
10
11. Antibiotic therapy
• Sulfonamides and broad
spectrum antibiotic drugs can
virtually sterilize the lumen of
the intestine, thus removing an
important source of vitamin K.
• Patients on antibiotic therapy
can be at risk of vitamin K
deficiency.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
11
12. Antibiotic therapy
Cases of hypoprothrominemia have been
identified in association with the use of
penicillin, semisynthetic penicillins and
cephalosporins.
Cephalosporin-type antibiotics can inhibit the
vitamin K-dependent carboxylase to produce
coumarin-like depressions of the activities
of the vitamin K-dependent clotting factors.
The β-lactam antibiotics are very weak
anticoagulants, the effects of which are
observed only in patients of low vitamin K
status.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
12
13. Neonates
Neonates are at special risk of
vitamin K deficiency!
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
13
14. Placental transport of the vitamin is
poor
Infants
have very
limited
reserves
of
vitamin K.
Their serum
levels are
typically
about half
those of
their
mothers.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
14
15. The neonatal intestine is sterile for the
first few days of life
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
15
16. Hepatic biosynthesis of the clotting factors
is inadequate in the young infant
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
16
17. Human milk is an inadequate source of
vitamin K
The frequency of vitamin
K-responsive hemorrhagic
disease in 1-month-old
infants is 1/4000 overall,
but 1/1700 among
breastfed infants.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
17
18. Neonates
Neonatal intestine
The neonatal intestine is
sterile for the first few
days of life!
Human milk
Human milk is an
inadequate source of
vitamin K!
Placental transport
Placental transport of
the vitamin is poor!
Hepatic biosynthesis
Hepatic biosynthesis of the
clotting factors is inadequate in
the young infant!
Vitamin K
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
18
19. Hemorrhagic disease of the newborn
• Some infants will develop
hemorrhage if continuing intake of
vitamin K is not provided.
• This condition of vitamin K deficiency
bleeding (VKDB), also called hemorrhagic
disease of the newborn, can present in
different ways, depending on the age of
the infant.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
19
20. Hemorrhagic disease of the newborn
Newborns (first 24
hours):
cephalohematoma,
intracranial,
intrathoracic or
intra-abdominal
bleeding.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
20
21. Hemorrhagic disease of the newborn
• Newborns (first week):
generalized ecchymoses of the
skin, bleeding from the
gastrointestinal tract, umbilical
cord stump or circumcision site.
• Infants (1–12 weeks):
intracranial, skin or
gastrointestinal bleeding.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
21
22. Hemorrhagic disease of the newborn
The major risk factors are:
• exclusive breast feeding
• failure to give vitamin K
prophylaxis
• certain maternal drug
therapies
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
22
23. Hemorrhagic disease of the newborn
• Exclusively breastfed infants who have
not received vitamin K or who have
gastrointestinal disorders involving lipid
malabsorption (cystic fibrosis, biliary
atresia, α1-antitrypsin deficiency) can
show signs within several weeks as
intracranial hemorrhage with liver
disease, central nervous system damage,
and high mortality due to bilirubinemia.
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
23
24. Hemorrhagic disease of the newborn
Infants fed formula diets are at lower risk
probably because of the greater amounts
of vitamin K in infant formulas than in
human milk.
This disease has also been reported
for newborns of mothers on
anticonvulsant therapy.
It has become a common practice in many
countries to treat all infants at birth with
parenterally administered vitamin K (1 mg
phylloquinone).
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
24
25. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 12, 2018 25