Vitamin K deficiency symptoms


Signs of Vitamin K Deficiency


The predominant clinical sign of vitamin K deficiency is hemorrhage (Table 8.13), which can lead to a fatal anemia. The blood shows prolonged clotting time and hypoprothrombinemia. Because a 50% loss of plasma prothrombin level is required to affect prothrombin time, prolongation of the latter is a useful biomarker for advanced subclinical vitamin D deficiency. Several congenital disorders of vitamin K-dependent proteins have been identified in human patients: at least a dozen forms of congenital dysprothrombinemia, at least three variants of factor VII, and a congenital deficiency of protein C. Patients with these disorders show coagulopathies; none responds to high doses of vitamin K.

Vitamin K deficiency

Undercarboxylated Proteins

A more sensitive indicator of low vitamin K status is the presence in plasma of under-γ-carboxylated vitamin K-dependent proteins. The first was originally thought to be a distinct protein produced only in vitamin K deficiency; it was referred to as the protein induced by vitamin K absence (PIVKA). Subsequently, it became clear that PIVKA was actually inactive prothrombin lacking residues required for its Ca2binding. It is thus useful as a marker for subclinical vitamin K deficiency. Another marker is under-γ-carboxylated osteocalcin, which is released from bone into the circulation. Studies have shown that increases in the serum concentrations of these factors are more sensitive to minidose warfarin therapy than are decreases in prothrombin or osteocalcin. Except for patients on anticoagulant therapy, undercarboxylation of blood-clotting factors is rare. The undercarboxylation of osteocalcin, however, is frequent among postmenopausal women.

Importance of Hindgut Microbial Biosynthesis

Vitamin K deficiency is rare among humans and most other animal species, the important exception being the rapidly growing chick raised in a wire-floored cage. This is due to the wide occurrence of vitamin K in plant and animal foods, and to the significant microbial synthesis of the vitamin that occurs in the intestines of most animals. In fact, for many species, including humans, the intestinal synthesis of vitamin K appears to meet normal needs. Species with short gastrointestinal tracts and very short intestinal transit times (e.g., about 8 hours in the chick), less than the generation  times of many bacteria, do not have well-colonized guts. Being thus unable to harbor vitamin K-producing bacteria, they depend on their diet as the source of their vitamin K.

Risk Factors for Vitamin K Deficiency

The most frequent causes of vitamin K deficiency, thus, are factors that interfere with the microfloral production or absorption of the vitamin:

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.

Anticoagulant therapy. Certain types of drugs can impair vitamin K function. These include warfarin and other 4-hydroxycoumarin anticoagulants, and large doses of salicylates, which inhibit the redox cycling of the vitamin. In each case, 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.

Antiobiotic therapy. Sulfonamides and broad-spectrum antibiotic drugs can virtually sterilize the lumen of the intestine, thus removing an important source of vitamin K for most animals. Therefore, it has been thought that patients on antibiotic therapy can be at risk of vitamin K deficiency.47 Indeed, cases of hypoprothrominemia have been identified in association with the use of penicillin, semisynthetic penicillins, and cephalosporins. In fact, the prevalence of such cases appeared to increase in the 1980s with the introduction of the β-lactam antibiotics.48 Although these drugs are administered intravenously, it is possible that they may affect enteric bacterial metabolism via biliary release. Studies have shown that not all patients treated with β-lactam antibiotics show altered fecal menaquinones, although they show significant increases in circulating  vitamin K-2,3-epoxide levels when treated with vitamin K. This observation led to the demonstration that the 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. Unlike the coumarins, however, the β-lactam antibiotics are very weak anticoagulants, the effects of which are observed only in patients of low vitamin K status.


Neonates are at special risk of vitamin K deficiency for several reasons:

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. The neonatal intestine is sterile for the first few days of life. The neonatal intestine thus does not provide an enteric microbial source of the vitamin. l Hepatic biosynthesis of the clotting factors is inadequate in the young infant. The plasma prothrombin concentrations of fetuses and infants are typically onequarter those of their mothers. Human milk is an inadequate source of vitamin K. The frequency of vitamin K-responsive hemorrhagic disease in 1-month-old infants is 1/4,000 overall, but 1/1,700 among breastfed infants. For these reasons, some infants49 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:

 newborns (first 24 hours) – cephalohematoma; intracranial, intrathoracic or intra-abdominal bleeding

newborns (first week) – generalized ecchymoses of the skin; bleeding from the gastrointestinal tract, umbilical cord stump or circumcision site l infants (1–12 weeks) – intracranial, skin or gastrointestinal bleeding. The major risk factors for VKDB are exclusive breastfeeding, failure to give vitamin K prophylaxis, and certain maternal drug therapies. 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. That infants fed formula diets are at lower risk probably relates to the greater amounts of vitamin K in infant formulas than human milk. Hemorrhagic disease has also been reported for newborns of mothers on anticonvulsant therapy.

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