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Vitamin K1

CPT: 84597
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Synonyms

  • Phylloquinone

Expected Turnaround Time

4 - 6 days


Related Documents


Specimen Requirements


Specimen

Serum or plasma, protected from light


Volume

1.0 mL


Minimum Volume

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


Container

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.


Collection

The blood is to be collected by venipuncture into a Vacutainer® blood collection tube and mixed immediately by gentle inversion at least six times to ensure adequate mixing. Allow serum samples to clot for at least 10 minutes. Separate plasma/serum from red cells by centrifugation.

Protect from light. Transfer plasma/serum specimen to labeled amber plastic transport tube with amber stopper. For amber plastic transport tube and amber stopper, order Labcorp No. 23598.


Storage Instructions

Specimens should be light-protected, and shipped at room temperature or refrigerated (preferred).


Stability Requirements

Temperature

Period

Room temperature

7 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3


Patient Preparation

Patient should fast for 12 hours.


Causes for Rejection

Receipt of mild or grossly lipemic specimen; receipt of grossly hemolyzed specimen; receipt of specimen not protected from light; receipt of specimen outside of stability; receipt of citrate plasma


Test Details


Use

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.


Limitations

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 specimens1,2 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.


Methodology

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


Reference Interval

0.10 – 2.20 ng/mL


Additional Information

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


Footnotes

1. Cham BE, Smith JL, Colquhoun DM. Interdependence of serum concentrations of vitamin K1, vitamin E, lipids, apolipoprotein A1, and apolipoprotein B: importance in assessing vitamin status. Clin Chim Acta. 1999 Sep;287(1-2):45–57.10509895
2. Azharuddin MK, O’Reilly DSJ, Gray A, Talwar D. HPLC Method for Plasma Vitamin K1: Effect of Plasma Triglyceride and Acute-Phase Response on Circulating Concentrations. Clin Chem. 2007 Sep;53(9):1706-1713.17712007
3. Analytical Validation Report for Vitamin K1 in Plasma and Serum by LC-MS/MS. VR-CET-RD-2020-21 Version 1; effective: Feb. 8, 2021.
4. Cranenburg EC, Schurgers LJ, Vermeer C. Vitamin K: the coagulation vitamin that became omnipotent. Thromb Haemost. 2007 Jul;98(1):120-125.17598002
5. Schurgers LJ, Teunissen KJ, Hamulyák K, Knapen MHJ, Vik H, Vermeer C. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007 Apr 15;109(8):3279-3283.17158229
6. Van Winckel M, De Bruyne R, Van De Velde S, Van Biervliet S. Vitamin K, an update for the paediatrician. Eur J Pediatr. 2009 Feb;168(2):127-134.18982351
7. Vermeer C. Vitamin K: the effect on health beyond coagulation - an overview. Food Nutr Res. 2012;56.22489224
8. Mann KG. Biochemistry and physiology of blood coagulation. Thromb Haemost. 1999 Aug;82(2):165-174.10605701
9. Walther B, Karl JP, Booth SL, Boyaval P. Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr. 2013 Jul 1;4(4):463-467.23858094
10. Shearer MJ, Fu X, Booth SL. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr. 2012 Mar 1;3(2):182-195.22516726
11. Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost. 2008 Oct;100(4):530-547.18841274
12. Theuwissen E, Teunissen KJ, Spronk HMH, et al. Effect of low-dose supplements of menaquinone-7 (vitamin K2) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. J Thromb Haemost. 2013 Jun;11(6):1085-1092.
13. Sconce E, Avery P, Wynne H, Kamali F. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood. 2007 Mar 15;109(6):2419-2423.17110451
14. Stafford DW, Roberts HR, Vermeer C. Vitamin K supplementation during oral anticoagulation: concerns. Blood. 2007 Apr 15;109(8):3607; author reply 3607-3608.17409344
15. Araki S, Shirahata A. Vitamin K Deficiency Bleeding in Infancy. Nutrients. 2020 Mar 16;12(3):780.32187975
16. Sankar MJ, Chandrasekaran A, Kumar P, Thukral A, Agarwal R, Paul VK.. Vitamin K prophylaxis for prevention of vitamin K deficiency bleeding: a systematic review. J Perinatol. 2016 May;36 Suppl 1(Suppl 1):S29-35.27109090
17. Theuwissen E, Magdeleyns EJ, Braam LA, et al. Vitamin K status in healthy volunteers. Food Funct. 2014 Feb;5(2):229-234.24296867
18. Bügel S. Vitamin K and bone health in adult humans. Vitam Horm. 2008;78:393-416.18374202

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
121200 Vitamin K1 9622-2 121201 Vitamin K1 ng/mL 9622-2

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