Vitamin K deficiency Domina Petric, MD

Signs of Vitamin K deficiency November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Coagulopathy Patients with dysprothrombinemia (factor VII, congenital deficiency of protein C) show coagulopathies. None respond to high doses of vitamin K! November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Undercarboxylated proteins A more sensitive indicator of low vitamin K status is the presence in plasma of under-γ-carboxylated vitamin K-dependent proteins. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Undercarboxylated proteins Protein Induced by Vitamin K Absence (PIVKA) Under-γ-Carboxylated Osteocalcin November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Risk factors for vitamin K deficiency November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Lipid malabsorption Diseases of the gastrointestinal tract, biliary stasis, liver disease, cystic fibrosis, celiac disease and Ascaris infection can interfere with the enteric absorption of vitamin K. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Neonates are at special risk of vitamin K deficiency! November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

The neonatal intestine is sterile for the first few days of life The neonatal intestine does not provide an enteric microbial source of the vitamin. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Hepatic biosynthesis of the clotting factors is inadequate in the young infant The plasma prothrombin concentrations of fetuses and infants are typically one-quarter those of their mothers. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Neonates Human milk Placental transport Neonatal intestine Vitamin K Placental transport of the vitamin is poor! Human milk Vitamin K Neonatal intestine Human milk is an inadequate source of vitamin K! The neonatal intestine is sterile for the first few days of life! Hepatic biosynthesis Hepatic biosynthesis of the clotting factors is inadequate in the young infant! November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Hemorrhagic disease of the newborn Newborns (first 24 hours): cephalohematoma, intracranial, intrathoracic or intra-abdominal bleeding. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Hemorrhagic disease of the newborn The major risk factors are: exclusive breast feeding failure to give vitamin K prophylaxis certain maternal drug therapies November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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. November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

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). November 11, 2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008.

Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. November 11, 2018