The chief manifestation of vitamin K deficiency is an increased bleeding tendency (see discussion of hypoprothrombinemia in section on oral anticoagulants, above). Ecchymoses, epistaxis, hematuria, GI bleeding, and postoperative hemorrhage are common; intracranial hemorrhage may occur. Hemoptysis is uncommon. The discovery of a vitamin K-dependent protein in bone suggests that the fetal bone abnormalities associated with the administration of oral anticoagulants during the first trimester of pregnancy ("fetal warfarin syndrome") may be related to a deficiency of the vitamin.
Evidence indicates a role for vitamin K in adult skeletal maintenance and osteoporosis. Low concentrations of the vitamin are associated with deficits in bone mineral density and fractures; vitamin K supplementation increases the carboxylation state of osteocalcin and also improves bone mineral density, but the relationship of these two effects is unclear. Bone mineral density in adults is not changed by therapeutic use of oral anticoagulants, but new bone formation may be impaired.
ABSORPTION, FATE, AND EXCRETION
The mechanism of intestinal absorption of compounds with vitamin K activity varies with their solubility. In the presence of bile salts, phylloquinone and the menaquinones are adequately absorbed from the intestine, almost entirely by way of the lymph. Phylloquinone is absorbed by an energy-dependent, saturable process in proximal portions of the small intestine; menaquinones are absorbed by diffusion in the distal portions of the small intestine and in the colon. Following absorption, phylloquinone is incorporated into chylomicrons in close association with triglycerides and lipoproteins. The extremely low phylloquinone levels in newborns may be partly related to very low plasma lipoprotein concentrations at birth and may lead to an underestimation of vitamin K tissue stores. Absorbed phylloquinone and menaquinones are concentrated in the liver, but the concentration of phylloquinone declines rapidly. Menaquinones, produced in the lower bowel, are less biologically active than phylloquinone due to their long side chain. Very little vitamin K accumulates in other tissues.
Apparently, there is only modest storage of vitamin K in the body. Under circumstances in which lack of bile interferes with absorption of vitamin K, hypoprothrombinemia develops slowly over a period of several weeks.
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