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Vitamin K deficiency
Domina Petric, MD
Signs of Vitamin K deficiency
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
2
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
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
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
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
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
Risk factors for vitamin K
deficiency
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
8
Lipid malabsorption
April 12, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
9
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 12, 2018 25

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Vitamin K deficiency

  • 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