Vitamin K₁

Serum or plasma, protected from light

1.0 mL

0.5 mL (Note: This volume does not allow for repeat testing.)

EDTA (lavender-top) plasma, preferred. Also acceptable are lithium heparin (green-top) plasma, gel-separated (SST) serum, and standard (red-top) serum. For amber plastic transport tube and amber-top, order Labcorp No. 23598.

Patient should fast for 12 hours.

This test is used for the assessment of vitamin K deficiency. Vitamin K deficiency may be induced by obstructive liver disease, obstructive icterus, malabsorption due to celiac disease, pancreatitis, diarrhea, and antibiotic abuse; may be used to treat blood clotting disorders, bone metabolism disorders, and hemorrhagic disorders of newborns.

Overnight (12-hour) patient fasting is required. Consumption of supplements or food with Vitamin K may elevate plasma concentrations of Vitamin K1 for testing.

Although lipemia does not interfere with the analytical measurement of Vitamin K1 by this test, Vitamin K1 levels are correlated with lipoprotein concentrations. As such, all lipemic samples should be rejected given Vitamin K1 levels are expected to be elevated in lipemic specimens^1,2 and prevent evaluation for Vitamin K1 insufficiency.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)³

0.10 – 2.20 ng/mL

Vitamin K serves as a critical cofactor for the post-translational carboxylation of glutamate residues of a number of proteins.^4-7 Gamma carboxylated glutamate (Gla) residues act as calcium-binding moieties and are essential for the function of these proteins. Profound vitamin K deficiency, caused by inadequate dietary intake or malabsorption, is an acute, life-threatening condition associated with excessive bleeding. Gla-containing coagulation factors II, VII, IX, and X, and proteins C and S, play critical roles in hemostasis.⁸ The Gla-proteins involved in blood coagulation are all synthesized in the liver. Several more recently discovered Gla-proteins that are synthesized in a wide variety of tissues serve roles in metabolic processes beyond coagulation. These proteins include osteocalcin, matrix Gla-protein (MGP), and growth arrest sequence-6 protein (Gas6) that serve key roles in maintaining bone strength, arterial calcification inhibition, and cell growth regulation, respectively. Many individuals with fully gamma-carboxylated coagulation factors have incomplete gamma-carboxylation of extra-hepatic Gla-proteins. It has been postulated that individuals with less than optimal dietary supply of vitamin K synthesize all clotting factors in their active form, whereas the gamma-carboxylation of other Gla-proteins is incomplete. This concept implies that prolonged sub-clinical vitamin K deficiency maybe a risk factor for conditions beyond bleeding, including osteoporosis and atherosclerosis.

Vitamin K is not a single compound, but rather a family of related compounds that all share a methylated naphthoquinone ring structure called menadione, substituted at the 3-position with a variable aliphatic side chain.^7,9-11 Vitamin K1 (also referred to as phylloquinone) is produced in plants and has a side chain that is composed of four isoprenoid residues, the last three of which are unsaturated. Green leafy vegetables such as spinach, broccoli, Brussels sprouts, and kale are especially good sources of vitamin K1. Vitamin K1 provides approximately 90% of the total vitamin K in the western diet.⁷

Oral anticoagulant drugs derived from coumarin block recycling of vitamin K to the form that is required as a cofactor for catalyzing the gamma carboxylation of proteins.¹¹ Despite the worldwide use of vitamin K antagonist drugs, there continues to be some uncertainties about the influence of dietary vitamin K on anticoagulation control.^12-14 The recommended dietary allowance for vitamin K intake is based on the hepatic requirement for clotting factor synthesis. Vitamin K deficiency in early infancy can cause of intra-cranial bleeding.¹² Newborn babies are at particular risk of vitamin K deficiency due to poor placental transfer and low levels of vitamin K in breast milk.⁶ Vitamin K prophylaxis at birth effectively prevents vitamin K deficiency bleeding (VKDB), also referred to as hemorrhagic disease of the newborn.^6,10,15,16

Some studies suggest that vitamin K intake above that required to maintain effective hemostasis may be needed to achieve an optimal extra-hepatic vitamin K status.^6,17 In 2001, the US Food and Nutrition Board concluded that there was insufficient data with which to establish a Recommended Daily Allowance (RDA) for vitamin K, in large part because of a lack of non-hemostatic endpoints that reflected adequacy of intake.¹⁰ The gamma-carboxylation of the Gla proteins in bone is required to bind calcium and to incorporate calcium into hydroxyapatite crystals of bone.¹⁸ The most highly studied of the known bone-related Gla-proteins is osteocalcin (OC).¹⁸ Vitamin K insufficiency is associated with an increase in the concentration of circulating under-carboxylated osteocalcin.¹⁸ Several clinical studies have reported favorable associations between vitamin K intake and bone health.^9,18 Other studies have suggested that vitamin K insufficiency may be associated with low bone mineral density and increased incidence of fractures.¹⁸

Matrix Gla-protein (MGP) is a vitamin K dependent Gla-protein found in bone, as well as in heart, kidney, and lung.¹⁸ MGP plays a role in the organization of bone tissue and serves as a potent inhibitor of arterial calcification. Incomplete carboxylation of MGP has been associated with an increased risk for developing vascular calcification.⁴ In healthy individuals, substantial fractions of osteocalcin and MGP circulate as incompletely carboxylated species, indicating that the majority of these individuals is sub-clinically vitamin K-deficient.⁴ Osteoporotic bone loss and vascular calcification are associated with treatment with oral anticoagulants, ostensibly due to the impairment of Gla-protein gamma carboxylation.⁴