LA NEWSLETTER
ABHORIZONS
FOR CLIENTS
New Procedures
Calcium-Sensing Receptor (CASR) Gene Sequencing Analysis
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 504513
CPT 81405
Synonyms CASR gene
Use CASR encodes the calcium sensing receptor (CaSR) which, when acti-
vated (1) inhibits secretion of parathyroid hormone (PTH), (2) stimulates
calcitonin release from the thyroid, and (3) stimulates urinary calcium
excretion. CASR mutations can result in calcium dysregulation:
• Heterozygous inactivating mutations cause familial hypocalciuric
hypercalcemia (FHH)
• Homozygous inactivating mutations cause neonatal severe hyper-
parathyroidism (NSHPT)
• Heterozygous activating mutations cause autosomal dominant hypo-
calcemia (ADH) or Bartter syndrome type V
Detection rates range from 18-70% for hypercalcemia and approximate-
ly 40% for hypocalcemia, as there are additional genes that affect calcium
regulation.
Identification of CASR mutations can be used to:
• Determine the cause of hypercalcemia in patients considering
parathyroid surgery (CASR mutations are not usually associated with PTH-
producing tumors)
• Confirm the diagnosis of NSHPT, leading to urgent parathyroidec-
tomy
• Identify individuals with ADH who are at risk for developing kidney
stones with vitamin D supplements
• Influence treatment options with calcimimetic or calcilytic therapies
Limitations Mutations that are not in exons 2 through 7 are not analyzed
and will not be detected. Polymorphisms at PCR primer target sites may
lead to false-negative results. This method will not detect changes in CASR
gene copy number or in other genes that affect calcium homeostasis.
This test was developed and its performance characteristics determined
by LabCorp. It has not been cleared or approved by the US Food and
Drug Administration (FDA).
Methodology Polymerase chain reaction (PCR) and Sanger sequencing of
targeted CASR exons, gel electrophoresis
Specimen Whole blood
Volume 3.0 mL
Minimum Volume 1.0 mL
Container Lavender-top (EDTA) tube or yellow-top (ACD) tube
Storage Instructions Room temperature
Causes for Rejection Serum or plasma specimens; frozen samples; hemo-
lyzed samples
Special Instructions This assay is currently not available in New York.
Testing is performed at Esoterix Endocrinology Laboratory.
References
Cole DE, Yun FH, Wong BY, et al. Calcium-sensing receptor mutations and denaturing
high performance liquid chromatography. J Mol Endocrinol. 2009 Apr;42(4):331-339.
PubMed 19179454
Hannan FM, Nesbit MA, Zhang C, et al. Identification of 70 calcium-sensing receptor
mutations in hyper- and hypo-calcaemic patients: evidence for clustering of extracellular
domain mutations at calcium-binding sites. Hum Mol Genet. 2012 Jun 15;21(12):2768-
2778. PubMed 22422767
Lienhardt A, Bai M, Lagarde JP, et al. Activating mutations of the calcium-sensing recep-
tor: management of hypocalcemia. J Clin Endocrinol Metab. 2001 Nov;86(11):5313-5323.
Volume XVII, No. 11 — November-December 2017
PubMed 11701698
Nissen PH, Christensen SE, Heickendorff L, Brixen K, Mosekilde L. Molecular genetic anal-
ysis of the calcium sensing receptor gene in patients clinically suspected to have familial
hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish
population. J Clin Endocrinol Metab. 2007 Nov;92(11):4373-4379. PubMed 17698911
Pidasheva S, D’Souza-Li L, Canaff L, Cole DE, Hendy GN. CASRdb: calcium-sensing recep-
tor locus-specific database for mutations causing familial (benign) hypocalciuric hypercal-
cemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia.
Hum Mutat. 2004 Aug;24(2):107-111. PubMed 15241791
Pollak MR, Chou YH, Marx SJ, et al. Familial hypocalciuric hypercalcemia and neonatal
severe hyperparathyroidism: effects of mutant gene dosage on phenotype. J Clin Invest.
1994 Mar;93(3):1108-1112. PubMed 8132750
Vahe C, Benomar K, Espiard S, et al. Diseases associated with calcium-sensing receptor.
Orphanet J Rare Dis. 2017 Jan 25;12(1):19. PubMed 28122587
IDH1/IDH2 Mutation Analysis . . . . . . . . . . . . . . . . . . . . . 481484
CPT 81403(x2); 88381
Synonyms IDH1; IDH2; Isocitrate dehydrogenase 1 and 2; NADP+
Use Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are the most
frequently mutated metabolic genes in human cancer. They encode
cytosolic and mitochondrial enzymes that catalyze the conversion of
isocitrate to a-ketoglutarate (aKG), a key component in metabolic and
cellular pathways including the Krebs cycle. IDH1 and IDH2 mutations are
found in multiple types of human cancer including, but not limited to,
acute myeloid leukemia and gliomas. Identification of IDH mutations can
aid in their diagnosis, provide prognostic information, and suggest treat-
ment with IDH inhibitors. This assay will detect mutations affecting amino
acids 100, 105, and 132 of IDH1, and amino acids 140 and 172 of IDH2.
Limitations In vitro studies indicate that this assay has a sensitivity to
detect approximately 5% mutated IDH1/2 in a background of non-
mutant DNA. Mutations present at a level below the detection sensitivity
or outside the analyzed region of the IDH1 and IDH2 genes will not be
detected by this assay.
This test was developed, and its performance characteristics determined,
by LabCorp. It has not been cleared or approved by the US Food and
Drug Administration (FDA).
Methodology SNaPshot Multiplex PCR (primer extension-based method)
Specimen Whole blood, bone marrow, formalin-fixed, paraffin-embedded
(FFPE) tissue block or slides
Volume 3 to 7 mL whole blood, 1 to 2 mL bone marrow, four pre-cut
unstained slides at 5 micron with one matching H&E reference slide, or
formalin-fixed, paraffin-embedded tissue (FFPE) block
Minimum Volume 3 mL whole blood, 1 mL bone marrow, two unstained
slides at 5um and one matching H&E slide, or three unstained slides
These new/revised publications are now available:
• Lipids in Atherosclerotic Cardiovascular Disease (ASCVD) Risk Assessment
and Management LABupdate (L17806)
• Rheumatoid Arthritis Brochure (L15239)
• ReproSURE™ Patient Information Brochure (L17031)
Please ask your LabCorp service representative for these titles.
 Volume XVII, No. 11 LabHorizons November-December 2017
at 5um. Tumor surface area >=4mm2 tumor area and >/= 50% tumor
content are preferred
Container Lavender-top (EDTA) tube, green-top (heparin) tube, yellow-
top (ACD) tube, FFPE tissue block and slide container
Storage Instructions Refrigerate. Maintain FFPE blocks/slides at room
temperature.
Causes for Rejection Specimen does not meet all of the above criteria
for sample type, container, minimum volume, collection and storage;
unsuitable specimens include but are not limited to: frozen whole blood
or marrow; a leaking tube; clotted blood or marrow; a grossly hemolyzed
specimen or otherwise visibly degraded; specimen suspected of being
contaminated by another specimen; specimen contains suspicious for-
eign material; no tumor tissue in FFPE block or slides; broken or stained
slides
Special Instructions Please provide a copy of the pathology report.
IDH1/2 testing will be delayed if the pathology report is not received.
Please direct any questions regarding this test to to customer service at
800-345-4363.
Note: This test is not available for New York clients.
References
Clark O, Yen K, Mellinghoff IK. Molecular Pathways: Isocitrate dehydrogenase mutations
in cancer. Clin Cancer Res. 2017 Apr 15;22(8):1837-1842. PubMed 26819452
Dang L, Yen K, Attar EC. IDH mutations in cancer and progress toward development of
targeted therapeutics. Ann Oncol. 2016 Apr;27(4):599-608. PubMed 27005468
Medeiros BC, Fathi AT, DiNardo CD, Pollyea DA, Chan SM, Swords R. Isocitrate dehydro-
genase mutations in myeloid malignancies. Leukemia. 2017 Feb;31(2):272-281. PubMed
27721426
Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer
Res. 2013 Feb 15;19(4):764-772. PubMed 23209033
Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009
Feb 19;360(8):765-773. PubMed 19228619
Lipoprotein-Associated Phospholipase A2 Activity . . . 123283
CPT 83698
Synonyms PLAC®
Test Includes Quantitation of Lp-PLA2 activity in serum or plasma
Use The PLAC® test for Lp-PLA2 Activity is an enzyme assay for the in vitro
quantitative determination of Lp-PLA2 (lipoprotein-associated phospholi-
pase A2) activity in EDTA plasma and serum. Lp-PLA2 activity is to be used
in conjunction with clinical evaluation and patient risk assessment as an
aid in predicting risk of coronary heart disease (CHD) in patients with no
prior history of cardiovascular events.
Methodology Spectrophotometric, enzymatic assay
Reference Interval Reduced Risk: <225 nmol/min/mL; Increased Risk:
≥225 nmol/min/mL
Additional Information Lp-PLA2 is a calcium-independent phospho-
lipase A2 enzyme that is associated with both low-density lipoprotein
(LDL) and, to a lesser extent, high-density lipoprotein (HDL) in human
plasma and serum1 and is distinct from other such phospholipases such
as cPLA2 and sPLA2.2,3 Lp-PLA2 is produced by macrophages and other in-
flammatory cells and is expressed in greater concentrations in advanced
atherosclerotic lesions than early-stage lesions.4,5
Several lines of evidence suggest that oxidation of LDL plays a critical
step in the development and progression of atherosclerosis.6,7 Lp-PLA2
participates in the breakdown of oxidized LDL in the vascular wall by hy-
drolyzing the oxidized phospholipid, producing lysophosphatidylcholine
and oxidized free fatty acids, both of which are potent pro-inflammatory
products that contribute to the formation of atherosclerotic plaques.8-10
Lp-PLA2 has demonstrated modest intra- and inter-individual variation,
commensurate with other cardiovascular lipid markers and substantially
less variability than high sensitivity C-reactive protein (hs-CRP). In addi-
tion, Lp-PLA2 is not elevated in systemic inflammatory conditions, and
may be a more specific marker of vascular inflammation. The relatively
small biological variation of Lp-PLA2 and its vascular specificity are of
value in the detection and monitoring of cardiovascular risk.11-13
Specimen Serum (preferred) or plasma
Volume 0.5 mL
Minimum Volume 0.2 mL
Container Red-top tube, gel-barrier tube, or lavender-top (EDTA) tube
Patient Preparation Fasting is not required.
2
Collection Separate serum or plasma from cells as soon as possible
(within two hours).
Storage Instructions Refrigerate, stable for 14 days. Stable at room
temperature for 24 hours and frozen up to 18 months. Ship refrigerated
on cool packs.
Causes for Rejection Hemolyzed samples; excessive turbidity; clots in
samples
Footnotes
1. Zalewski A, Macphee C. Role of lipoprotein-associated phospholipase A2 in athero-
sclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler Thromb Vasc
Biol. 2005 May;25(5):923-931. PubMed 15731492
2. Kudo I, Murakami M. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat.
2002 Aug;68-69:3-58. PubMed 12432908
3. Burke JE, Dennis EA. Phospholipase A2 structure/function, mechanism, and signaling. J
Lipid Res. 2009 Apr;50:s237-242. PubMed 19011112
4. Hakkinen T, Luoma JS, Hiltunen MO, et al. Lipoprotein-associated phospholipase A(2),
platelet-activating factor acetylhydrolase, is expressed by macrophages in human and
rabbit atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 1999 Dec;19(12):2909-2917.
PubMed 10591668
5. Kolodgie FD, Burke AP, Skorija KS, et al. Lipoprotein-associated phospholipase A2 pro-
tein expression in the natural progression of human coronary atherosclerosis. Arterioscler
Thromb Vasc Biol. 2006 Nov;26(11):2523-2529. PubMed 16960105
6. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet. 1994
Sep;344(8925):793-795. PubMed 7916078
7. Chisolm GM, Steinberg D. The oxidative modification hypothesis of atherogenesis: an
overview. Free Radic Biol Med. 2000 Jun 15;28(12):1815-1826. PubMed 10946223
8. Macphee CH, Moores KE, Boyd HF, et al. Lipoprotein-associated phospholipase A2,
platelet-activating factor acetylhydrolase, generates two bioactive products during
the oxidation of low-density lipoprotein: use of a novel inhibitor. Biochem J. 1999 Mar
1;338(Pt 2):479-487. PubMed 10024526
9. Macphee CH. Lipoprotein-associated phospholipase A2: a potential new risk factor for
coronary artery disease and a therapeutic target. Curr Opin Pharmacol. 2001 Apr;1(2):121-
125. PubMed 11714085
10. Suckling KE, Macphee CH. Lipoprotein-associated phospholipase A2: a target
directed at the atherosclerotic plaque. Expert Opin Ther Targets. 2002 Jun;6(3):309-314.
PubMed 12223071
11. Wolfert RL, Kim NW, Selby RG, Sarno MJ, Warnick GR, Sudhir K. Biological variability
and specificity of lipoprotein-associated phospholipase A2 (Lp-PLA), a novel marker of
cardiovascular risk (abstract). Circulation. 2004;110(Supplement 3):309.
12. Lerman A, McConnell JP. Lipoprotein-associated phospholipase A2: a risk marker or a
risk factor? Am J Cardiol. 2008 Jun 16;101(12A):11F-22F. PubMed 18549867
13. Thompson A, Gao P, Orfei L, et al. Lipoprotein-associated phospholipase A(2) and risk
of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies.
Lancet. 2010 May 1;375(9725):1536-1544. PubMed 20435228
Multiple Myeloma Cascade With Reflex to sIFE and sFLC . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123200
CPT 84155; 84165
Test Includes A Serum Protein Electrophoresis (SPEP) test is first run. If the
SPEP is:
1. Positive (ie, M-Protein present), a serum Immunofixation (sIFE)
test is automatically ordered and run (at additional charge). This reflexed
test serves to identify the M-protein’s heavy and light chain components
(eg, “IgG Kappa”). This finding will be reported and no further reflex test-
ing will occur.
2. Negative (ie, no M-Protein seen), a serum Free Light Chain (sFLC)
test is automatically ordered and run (at additional charge). Then:
• If the sFLC is Positive (ie, abnormal K/L ratio), a serum Immunofixa-
tion (sIFE) test is automatically ordered and run (at additional charge).
This reflexed test serves to identify the M- protein’s heavy and light
chain components (eg, “IgG Kappa”). This finding will be reported and no
further reflex testing will occur.
• If the sFLC is Negative (ie, no abnormal K/L ratio), no further reflex
testing will occcur. A recommendation comment will be added to the
report to “Consider ordering urine Immunofixation (uIFE) to rule out
Amyloidosis (AL).”
Use To maximize the clinical sensitivity of Serum Protein Electrophoresis
(SPEP) when screening for plasma cell dyscrasias.
Methodology SPEP: Protein electrophoresis on agarose media; IFE:
Electrophoresis followed by immunodiffusion against monospecific
antisera to immunoglobulin and individual heavy and light chains; Ig
Quant: turbidimetric quantitation of IgG, IgA, and IgM; sFLC: immuno-
logic quantitation
 Volume XVII, No. 11 LabHorizons November-December 2017

Additional Information The analytical sensitivity of the commonly used Table 1 below in accordance with the approved therapeutic product
serum tests for Multiple Myeloma (MM) screening is: SPEP < sIFE < sFLC labeling.
with SPEP being the least sensitive and sFLC being the most sensitive
Table 1: List of Variants for Therapeutic Use
detector of M-proteins.1
According to the International Myeloma Working Group (IMWG) guide- Gene Variant Targeted Therapy
lines, addition of sFLC and IFE to SPEP can prevent false negatives and BRAF BRAF V600E Tafinlar® (dabrafenib) in combination
increases the detection of multiple myeloma to >99%.2 with MEKINIST® (trametinib)
Specimen Serum ROS1 ROS1 fusions XALKORI® (crizotinib)
Volume 5 mL
EGFR L858R, Exon 19 deletions IRESSA® (gefitinib)
Minimum Volume 3 mL
Container Red-top tube or gel-barrier tube Limitations The test is not indicated to be used for standalone diagnostic
Storage Instructions Refrigerate at 2°C to 8°C. purposes, screening, monitoring, risk assessment, or prognosis. Results
Stability other than those listed in Table 1 are indicated for use only in patients
Temperature Period
who have already been considered for all appropriate therapies. Safe
and effective use has not been established for selecting therapies using
Room temperature 3 days this device for the variants in Table 1 in tissue types other than NSCLC.
Refrigerated 14 days Analytical performance using NSCLC specimens has been established for
Frozen 14 days
the variants listed in Table 2.

Freeze/thaw cycles Stable x3 Table 2: List of Variants With Established Analytical Performance Only
Causes for Rejection Hemolysis; plasma instead of serum Gene Variant ID/type Nucleotide change
Footnotes KRAS COSM512 C.34_35delGGinsTT
1. Katzmann, JA. Screening panels for monoclonal gammopathies: time to change. Clin
Biochem Rev. 2009 Aug;30(3):105-111. PubMed 19841692 KRAS COSM516 c.34G>T
2. Dispenzieri A, Kyle R, Merlini G, et al. International Myeloma Working Group guidelines MET COSM707 c.3029C>T
for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia.
2009 Feb;23(2):215-224. PubMed 19020545 PIK3CA COSM754 c.1035T>A

Methodology The Oncomine® Dx Target Test-Lung is a qualitative

MLH1/MSH2/MSH6/PMS2/EPCAM Somatic Tumor MMR diagnostic test that uses targeted high-throughput, parallel-sequencing
technology to detect single-nucleotide variants (SNVs) and deletions in
Sequencing and Deletion/Duplication Test . . . . . . . . . 481472 23 genes from DNA and fusions in ROS1 from RNA isolated from formalin-
CPT Call client services. fixed, paraffin-embedded (FFPE) tumor tissue samples from patients with
Synonyms EPCAM; Hereditary Nonpolyposis Colorectal Cancer; HNPCC; non-small cell lung cancer (NSCLC) using the Ion PGM™ Dx Instrument
IMCAN Tumor; MLH1; MMR Somatic; MSH2; MSH6; PMS2 System.
Use Tumors with mismatch repair (MMR) deficiency as determined by MSI Specimen Formalin-fixed, paraffin-embedded (FFPE) tissue blocks or
or IHC are suspected for HNPCC, Lynch or Lynch-like syndrome. This test slides from NSCLC
will assess the tumor for a pathogenic genetic variant which, if found, Volume
may be evaluated in blood to determine germline/hereditary status.
Specimen Type Tumor Size mm2 Slides Requirement
Limitations This test was developed, and its performance characteristics
determined, by Impact Genetics. It has not been cleared or approved by Resection or Surgical ≥1, but <10 9 USS & 1 H&E
the US Food and Drug Administration (FDA). Biopsies
≥10 2 USS & 1 H&E
Methodology Next generation sequencing (NGS); Multiplex Ligation-
Core Needle Biopsies ≥1 9 USS & 1 H&E
Dependent Probe Amplification (MLPA); Sanger sequencing
Specimen Formalin fixed paraffin-embedded (FFPE) tissue; whole blood Minimum Volume Tumor surface area greater than or equal to 4mm2
Volume Formalin fixed paraffin embedded (FFPE) block (preferred) or tumor area; tumor content greater or equal to 10%. Resection or Surgical
19 serial unstained unbaked slides (5-10 microns thick) with 1 adjacent Biopsies: 1 H&E and 2 unstained slides (5 um). Core Needle Biopsies: 1
unstained unbaked slide (4 microns thick); Whole Blood: 8.5 mL H&E and 9 unstained slides (5 um)
Minimum Volume Whole blood: 4 mL Container FFPE block or slides
Container Lavender-top (EDTA) tube, yellow-top (ACD) tube, blocks or Collection Indicate date and time of collection on test request form.
slides Storage Instructions Room temperature
Collection Whole blood samples must be received at Impact Genetics Causes for Rejection Tumor block or slides containing no tumor; tumor
within five days of collection. area <1mm2; tumor content in the region of interest <10%; broken or
Storage Instructions Room temperature. Whole blood is stable at room stained slides
temperature for five days. Fixed tissue is stable indefinitely. Special Instructions Please provide a copy of the pathology report or re-
Causes for Rejection Coagulated blood lated ICD10 code on the requistion. Test will be delayed if the pathology
Special Instructions Testing referred to Impact Genetics, Ontario, Canada. report and clinical indication are not received. Please direct any questions
Pathology report with MSI or IHC required. Please direct any questions regarding this test to customer service at 800-345-4363.
regarding this test to 877-624-9769. References
References Oncomine® Dx Target Test User Guide, Rev C.0, 2017.
Haraldsdottir S, Hampel H, Tomsic J, et al. Colon and endometrial cancers with mismatch
repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterol-
ogy. 2014 Dec;147(6):1308-1316. PubMed 25194673 PD-L1 IHC (Nivolumab) Squamous Cell Carcinoma of the Head
and Neck . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481615
Oncomine® Dx Target Test-Lung . . . . . . . . . . . . . . . . . . . 481475 CPT 88360
CPT 81445; 88381 Synonyms OPDIVO®; Programmed Death Ligand 1
Synonyms NGS FDA Methodology Immunohistochemistry (IHC)
Use The Oncomine® Dx Target Test-Lung is indicated to aid in selecting Specimen Tissue
NSCLC patients for treatment with the targeted therapies listed in the Volume One formalin-fixed paraffin embedded (FFPE) tissue block or five

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 Volume XVII, No. 11 LabHorizons November-December 2017

unstained positively charged slides sectioned from FFPE tissue block at 4
to 5 microns.
Minimum Volume Three unstained tissue slides
Container Tissue block or slide
Collection Tissue should be fixed in 10% neutral buffered formalin for no
more than 72 hours. Embed in paraffin.
Storage Instructions Room temperature
Causes for Rejection Insufficient tissue; tumor other than non squamous
cell carcinoma of the head and neck
Special Instructions Please provide a copy of the pathology report.
Note: This test number is used for tracking oncology IHC specimens to
the laboratory. Bill codes will be added when testing is complete, based
on the processes performed in the laboratory.
PD-L1 IHC (Nivolumab) Urothelial Carcinoma . . . . . . . 481500
CPT 88360
Synonyms OPDIVO®; Programmed Death Ligand 1
Methodology Immunohistochemistry (IHC)
Specimen Tissue
Volume One formalin-fixed paraffin embedded (FFPE) tissue block or five
unstained positively charged slides sectioned from FFPE tissue block at 4
to 5 microns.
Minimum Volume Three unstained tissue slides
Container Tissue block or slide
Collection Tissue should be fixed in 10% neutral buffered formalin for no
more than 72 hours. Embed in paraffin.
Storage Instructions Room temperature
Causes for Rejection Insufficient tissue; tumor other than urothelial
carcinoma
Special Instructions Please provide a copy of the pathology report.
Note: This test number is used for tracking oncology IHC specimens to
the laboratory. Bill codes will be added when testing is complete, based
on the processes performed in the laboratory.

Service Announcement
Biotin Interference Affects Some Assays
LabCorp would like to make clinicians aware that some assays can be affected by high levels of biotin in a patient’s serum/plasma. Thinking it is a
contributor to keratin, some people have begun taking large doses of biotin to improve their hair, nails, and skin. Some clinicians prescribe high-
dose biotin in the treatment of multiple sclerosis or dermatologic conditions.

Over-the-counter formulations are available in a variety of names, including vitamin B7, vitamin H, and coenzyme R. These formulations can
contain nearly 1,000 times as much of the Institute of Medicine-recommended daily dose of 30 mcg.

Many modern immunoassays contain biotin along with streptavidin. The FDA is aware of people taking high levels of biotin that would interfere
with lab tests, and samples from patients taking high levels of biotin can produce falsely high or falsely low results, depending on the assay
mechanism. As such, it is important for physicians to remind patients to refrain from taking high levels of biotin for at least 72 hours prior to im-
munoassay test collection.

Below are some recommendations from the FDA’s Safety Communication on Biotin:

RECOMMENDATIONS:

“For Health Care Providers:

• Talk to your patients about any biotin supplements they may be taking, including supplements marketed for hair, skin, and nail growth.
• Be aware that many lab tests, including but not limited to cardiovascular diagnostic tests and hormone tests, that use biotin technology are
potentially affected, and incorrect test results may be generated if there is biotin in the patient’s specimen.
• Communicate to the lab conducting the testing if your patient is taking biotin.
• If a lab test result doesn’t match the clinical presentation of your patient, consider biotin interference as a possible source of error.
• Know that biotin is found in multivitamins, including prenatal multivitamins, biotin supplements, and dietary supplements for hair, skin, and
nail growth in levels that may interfere with lab tests.
• Report to the lab test manufacturer and the FDA if you become aware of a patient experiencing an adverse event following potentially incor-
rect laboratory test results due to biotin interference.”

References:
http://endocrinenews.endocrine.org/january-2016-thyroid-month-beware-of-biotin/. Accessed Dec. 20, 2016.
http://www.captodayonline.com/beauty-fads-ugly-downsidetest-interference/. Accessed Dec. 20, 2016.
https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm586641.htm. Accessed Dec. 4, 2017.

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 Volume XVII, No. 11 LabHorizons November-December 2017

Assays Potentially Affected by Biotin Interference

Test Name Test No. Test Name Test No.
α-Fetoprotein (AFP), Tumor Marker 002253 C-Peptide, Eight Specimens 015804
α-Fetoprotein (AFP), Tumor Marker (Serial Monitor) 480012 C-Peptide, 24-Hour Urine 003236
Amenorrhea Profile 031138 C-Telopeptide (Endocrine Sciences) 500089
Anti-dsDNA (Double-stranded) Antibodies 096339 Dehydroepiandrosterone (DHEA) Sulfate 004020
Adrenocorticotropic Hormone (ACTH), Plasma 004440 Dehydroepiandrosterone (DHEA) Sulfate, Two Specimens 144691
Adrenocorticotropic Hormone (ACTH), Plasma, Two Specimens 225250 Dehydroepiandrosterone (DHEA) Sulfate, Three Specimens 146315
Adrenocorticotropic Hormone (ACTH), Plasma, Three Specimens 038927 Dehydroepiandrosterone (DHEA) Sulfate, Four Specimens 146316
Adrenocorticotropic Hormone (ACTH), Plasma, Four Specimens 225268 Dehydroepiandrosterone (DHEA) Sulfate, Five Specimens 146317
Adrenocorticotropic Hormone (ACTH), Plasma, Five Specimens 038919 Dehydroepiandrosterone (DHEA) Sulfate, Six Specimens 146318
Adrenocorticotropic Hormone (ACTH), Plasma, Six Specimens 225276 Dehydroepiandrosterone (DHEA) Sulfate, Seven Specimens 146319
Adrenocorticotropic Hormone (ACTH), Plasma, Seven Specimens 038901 Dehydroepiandrosterone (DHEA) Sulfate, Eight Specimens 146321
Adrenocorticotropic Hormone (ACTH), Plasma, Eight Specimens 267708 Digoxin 007385
Anemia Profile B 042077 Digoxin, Random 007566
B-Type Natriuretic Peptide 140889 Estradiol 004515
Cancer Antigen (CA) 125 002303 Ferritin 004598
Cancer Antigen (CA) 125 in the Presence of Human Antimouse 144733 Ferritin (Serial Monitor) 480111
Antibodies (HAMA)
Folate (Folic Acid) 002014
Cancer Antigen (CA) 125 (Serial Monitor) 480061 Folate, RBC and Serum 285700
Cancer Antigen (CA) 15-3 143404 Follicle-stimulating Hormone (FSH) 004309
Cancer Antigen (CA) 15-3 (Serial Monitor) 483404 Follicle-stimulating Hormone (FSH) and Luteinizing Hormone (LH) 028480
Carbohydrate Antigen (CA) 19-9 002261 Follicle-stimulating Hormone (FSH), Two Specimens 208785
Carbohydrate Antigen (CA) 19-9 (Serial Monitor) 480053 Follicle-stimulating Hormone (FSH), Three Specimens 038935
Carcinoembryonic Antigen (CEA) 002139 Follicle-stimulating Hormone (FSH), Four Specimens 211292
Carcinoembryonic Antigen (CEA) (Serial Monitor) 480095 Follicle-stimulating Hormone (FSH), Five Specimens 038943
Colorectal Cancer Monitor Profile 485011 Follicle-stimulating Hormone (FSH), Six Specimens 211284
Cortisol 004051 Follicle-stimulating Hormone (FSH), Seven Specimens 208801
Cortisol, ACTH Stimulation 140761 Follicle-stimulating Hormone (FSH), Eight Specimens 208819
Cortisol, AM 104018 Free Androgen Index (FAI) 146688
Cortisol, AM & PM 104000 Galectin-3 With NT-proBNP 142005
Cortisol, PM 104026 Gastrin 004390
Cortisol, Two Specimens 024265 Gastrin, Two Specimens 208827
Cortisol, Three Specimens 028498 Gastrin, Three Specimens 038745
Cortisol, Four Specimens 026948 Gastrin, Four Specimens 039438
Cortisol, Five Specimens 039222 Gastrin, Five Specimens 038752
Cortisol, Six Specimens 024091 Gastrin, Six Specimens 204644
Cortisol, Seven Specimens 039214 Gastrin, Seven Specimens 034934
Cortisol, Eight Specimens 210823 Gastrin, Eight Specimens 211268
Creatine Kinase (CK), MB 120816 Glutamic Acid Decarboxylase (GAD) Autoantibody 143008
Creatine Kinase (CK), MB and Total 002311 Growth Hormone 004275
C-Peptide 010108 Growth Hormone, Two Specimens 026898
C-Peptide (Serial Monitor) 480108 Growth Hormone, Three Specimens 038844
C-Peptide, Two Specimens 143302 Growth Hormone, Four Specimens 045997
C-Peptide, Three Specimens 143333 Growth Hormone, Five Specimens 038836
C-Peptide, Four Specimens 143324 Growth Hormone, Six Specimens 004267
C-Peptide, Five Specimens 015798 Growth Hormone, Seven Specimens 038869
C-Peptide, Six Specimens 319609 Growth Hormone, Eight Specimens 208835
C-Peptide, Seven Specimens 015801 Hemoglobinopathy Profile With Reflex to α-Thalassemia 451363

5
 Volume XVII, No. 11 LabHorizons November-December 2017

Assays Potentially Affected by Biotin Interference (continued)

Test Name Test No. Test Name Test No.
Hepatitis A Antibody, IgM 006734 Insulin, Eight Specimens 014319
Hepatitis A Virus (HAV) Antibody, Total 006726 Liver Cancer Monitor Profile 485060
Hepatitis B Core Antibody, IgG, IgM, Differentiation 098418 Luteinizing Hormone (LH) 004283
Hepatitis B Core Antibody, IgM 016881 Luteinizing Hormone (LH), Two Specimens 026971
Hepatitis B Core Antibody, Total 006718 Luteinizing Hormone (LH), Three Specimens 039230
Hepatitis B Surface Antigen 006510 Luteinizing Hormone (LH), Four Specimens 026955
Hepatitis B Virus (HBV) Evaluation Profile 037215 Luteinizing Hormone (LH), Five Specimens 039248
Hepatitis Be Antigen 006619 Luteinizing Hormone (LH), Six Specimens 211227
Hepatitis C Virus (HCV) Antibody 140659 Luteinizing Hormone (LH), Seven Specimens 095448
Hepatitis C Virus (HCV) Antibody Verification 144090 Luteinizing Hormone (LH), Eight Specimens 211276
Hepatitis C Virus (HCV) Antibody With Reflex for HCV Antibody 144065 Myoglobin 010405
Verification
Neuroblastoma Monitor Profile 485052
Hepatitis C Virus (HCV) Antibody With Reflex to Qualitative NAA 144045
NT-proBNP 143000
Hepatitis C Virus (HCV) Antibody With Reflex to Quantitative Real-time 144050
Obstetric Panel With Fourth-generation HIV 231950
PCR
Ovarian Cancer Monitor 081610
Hepatitis Panel, Acute 322744
Ovarian Cancer Monitor Profile III 485110
Hepatitis Profile I (Diagnostic) 058560
Ovarian Malignancy Risk (ROMA®) 140045
Hepatitis Profile II (Diagnostic Follow-up) 046938
Ovarian Function Profile II 244004
Hepatitis Profile III (Patient Management) 045849
Pancreatic Cancer Monitor Profile 485086
Hepatitis Profile IV (Hepatitis A and B Immune Status) 058537
Parathyroid Hormone (PTH), Intact 015610
Hepatitis Profile VI (Hepatitis B Profile) 058545
Parathyroid Hormone (PTH) Plus Calcium 054601
Hepatitis Profile VII (Hepatitis A and B Profile) 058552
Prenatal Profile I With Hepatitis B Surface Antigen 202945
Hepatitis Profile VIII (Hepatitis B and C Profile) 255505
Procalcitonin 164750
Hepatitis Profile X (HBV Prevaccination Profile) 235473
Progesterone 004317
Hepatitis Profile XII (HBV Follow-up Profile) 091108
Prostate-specific Antigen (PSA) 010322
Hepatitis Profile XIII (HBV Prenatal Profile) 265397
Prostate-specific Antigen (PSA) (Serial Monitor) 480145
Hirsutism Profile 048462
Prostate-specific Antigen (PSA), Free:Total Ratio 480947
Human Chorionic Gonadotropin (hCG), β-Subunit, Qualitative 004556
Prostate-specific Antigen (PSA), Free:Total Ratio Reflex 480772
Human Chorionic Gonadotropin (hCG), β-Subunit, Quantitative 004416
Prostate-specific Antigen (PSA), Free:Total Ratio (Serial Monitor) 480780
Human Chorionic Gonadotropin (hCG), β-Subunit, Quantitative (Serial 480038
Monitor) Prostate-specific Antigen (PSA), Free:Total Ratio Reflex (Serial Monitor) 480640
Human Epididymis Protein 4 081700 Prostate-specific Antigen (PSA), Ultrasensitive 140731
Human Epididymis Protein 4 (Serial Monitor) 481700 Prostate-specific Antigen (PSA), Ultrasensitive (Serial Monitor) 140723
Human Immunodeficiency Virus 1/O/2 (HIV-1/O/2) Antigen/Antibody 083935
Sex Hormone-binding Globulin 082016
(Fourth Generation) Preliminary Test With Cascade Reflex to
Supplementary Testing T3 Uptake 001156
Inhibin A, Ultrasensitive 146803 Testicular Function Profile I 035741
Inhibin B 146795 Testicular Function Profile II 035113
Insulin 004333 Testicular Function Profile III 058925
Insulin and C-Peptide 213660 Testosterone Free, Profile I 140226
Insulin-like Growth Factor 1 (IGF-1) 010363 Testosterone Free, Profile II 070130
Insulin-like Growth Factor-1 (IGF-1) With Z Score 010540 Testosterone, Total 004226
Insulin-like Growth Factor-binding Protein 3 (IGFBP-3) 140152 Thyroglobulin Antibody 006685
Insulin, Two Specimens 146902 Thyroglobulin Antibody and Thyroglobulin, IMA or LC/MS-MS 042045
Insulin, Three Specimens 146993 Thyroglobulin Antibody and Thyroglobulin, IMA or RIA 042060
Insulin, Four Specimens 147074 Thyroid Antibodies 006684
Insulin, Five Specimens 147165 Thyroid Cascade Profile 330015
Insulin, Six Specimens 147256 Thyroid Peroxidase (TPO) Antibodies 006676
Insulin, Seven Specimens 147397 Thyroid Profile 000455

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 Volume XVII, No. 11 LabHorizons November-December 2017

Assays Potentially Affected by Biotin Interference (continued)

Test Name Test No. Test Name Test No.
Thyroid Profile II, Comprehensive 027011 Thyroxine (T4), Thyroxine-binding Globulin (TBG), and T4−TBG Index 004457
Thyroid Profile With TSH 000620 Thyroxine (T4) and Thyroid-stimulating Hormone (TSH) 024026
Thyroid-stimulating Hormone (TSH) 004259 Triiodothyronine (T3) 002188
Thyroid-stimulating Hormone (TSH) and Free T4 224576 Triiodothyronine (T3), Free 010389
Thyroid-stimulating Hormone (TSH) in Pregnancy 004593 Troponin I 120832
Thyrotropin Receptor Antibody, Serum 010314 Uterine Cancer Monitor Profile 485136
Thyroxine (T4) 001149 Vitamin B12 001503
Thyroxine (T4), Free, Direct 001974 Vitamin B12 and Folates 000810

Updates to the Directory of Services and Interpretive Guide (DoS)

Test Name Test No. Field/Change (Only fields that change are included here.)
α1-Antitrypsin, Fecal, Quantitative 123010 Causes for Rejection Nonfecal sample received (eg, serum, plasma, urine); sample taken from diaper unless
portion taken has not been in contact with diaper material; preserved stool received (eg, 10% Formalin, Mer-
thiolate Formalin, Sodium Acetate Formalin, or Polyvinyl Alcohol)
Alternaria alternata 602455 Synonyms Alternaria tenuis
Bordetella pertussis, Nasopharyngeal Culture 180224 Additional Information Nucleic Acid Amplification (NAA/PCR) procedures provide more rapid results and
have been increasingly used in the diagnosis of B pertussis infection. Studies have shown that the best yield is
obtained when PCR and culture are used to diagnose this infection.
C-Telopeptide (Endocrine Sciences) 500089 Methodology Electrochemiluminescence immunoassay (ECLIA)
Collection It is recommended to draw blood as fasting, morning samples. Samples should not be taken from
patients receiving therapy with high biotin doses (i.e. >5 mg/day) until at least 8 hours following the last biotin
administration.
Separate serum from cells within 45 minutes of collection. Transfer specimen to a plastic transport tube before
freezing. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit
separate frozen specimens for each test requested.
Calcitonin (Thyrocalcitonin) 004895 Stability
Temperature Period
Room temperature Unstable
Refrigerated Unstable
Frozen 90 days
Freeze/thaw cycles Stable x3

Calprotectin, Fecal 123255 Causes for Rejection Serum or plasma received; stool contaminated with urine; specimen older than 10 days of
collection before tested; samples taken from diapers unless portion taken has not been in contact with diaper
material; preserved stool received
Calreticulin (CALR) Mutation Analysis 489450 Use The calcium-binding endoplasmic reticulin chaperone protein, calreticulin (CALR), is somatically mutated
in approximately 70% of patients with JAK2-negative essential thrombocythemia (ET) and 60% to 88% of
patients with JAK2-negative primary myelofibrosis (PMF). Only a minority of patients (approximately 8%) with
myelodysplasia have mutations in CALR gene. CALR mutations are rarely detected in patients with de novo
acute myeloid leukemia, chronic myelogenous leukemia, lymphoid leukemia, or solid tumors. CALR mutations
are not detected in polycythemia and generally appear to be mutually exclusive with JAK2 mutations and MPL
mutations.
The majority of mutational changes involve a variety of insertion or deletion mutations in exon 9 of the
calreticulin gene: approximately 53% of all CALR mutations are a 52 bp deletion (type-1) while the second
most prevalent mutation (approximately 32%) contains a 5 bp insertion (type-2). Other mutations (non-type 1
or type 2) are seen in a small minority of cases. CALR mutations in PMF tend to be associated with a favorable
prognosis compared to JAK2V617F mutations, whereas primary myelofibrosis negative for CALR, JAK2V617F and
MPL mutations (so-called triple negative) is associated with a poor prognosis and shorter survival.
The detection of a CALR gene mutation aids in the specific diagnosis of a myeloproliferative neoplasm, and
helps distinguish this clonal disease from a benign reactive process.

Note: Please consult the online Directory of Services and Interpretive Guide at https://www.labcorp.com/tests for the most current test information.

7
 Volume XVII, No. 11 LabHorizons November-December 2017

Test Name Test No. Field/Change (Only fields that change are included here.)
Chlamydia/Gonococcus, NAA 183194 Container Gen-Probe® Aptima® swab or Aptima® urine specimen transport; ThinPrep® or SurePath™ liquid
cytology vials
Chlamydia/Gonococcus, NAA With Confirmation 183616
Chlamydia trachomatis, NAA 188078
Cyclic AMP, Plasma 004984 Stability
Temperature Period
Frozen 9 days
Freeze/thaw cycles Stable x3

Haptoglobin 001628 Use Decreased to absent levels occur more with intravascular than extravascular hemolysis: haptoglobin binds
hemoglobin, and carries it to the reticuloendothelial system. Thus, haptoglobin is useful in work-up for hemo-
lytic states. It is low in the megaloblastic anemias, which have a hemolytic component. It is decreased in infec-
tious mononucleosis. Decreases can occur with hematoma or tissue hemorrhage. Haptoglobin can be low with
liver disease. Congenital absence occurs (small fraction of certain ethnic populations have ahaptoglobinemia,
absence of detectable haptoglobin). Frequently elevated as an acute phase reactant, in inflammatory disorders
(eg, collagen diseases, infections, tissue destruction, and with advanced malignant neoplasms).1
Helicobacter pylori Urea Breath Test 180836 Specimen Breath samples pre- and post-ingestion of fruit-flavored powder solution, containing 13C-urea diag-
nostic component from adult patients.
Volume One pre- and one post-ingestion breath sample from adult patients.
Hemoglobin (Hb) A1c 001453 Minimum Volume Pediatric EDTA whole blood tubes may be used. Please place original labeled capillary tube
in a labeled transport tube for shipment to the laboratory.
Hemoglobin (Hb) A1c With eAG 102525
Lactoferrin, Fecal, Quantitative 123016 Causes for Rejection Nonfecal sample received (eg, serum, plasma, urine); stool contaminated with urine;
preserved stool received (eg, 10% formalin, sodium acetate formalin, or polyvinyl alcohol)
Neisseria gonorrhoeae, NAA 188086 Container Gen-Probe® Aptima® swab or Aptima® urine specimen transport; ThinPrep® or SurePath™ liquid
cytology vials
Organic Acid Analysis, Urine 716720 Stability

Temperature Period
Frozen 12 months

Pancreatic Elastase, Fecal 123234 Causes for Rejection Serum or plasma received; stool contaminated with urine; watery or unformed (loose)
stool submitted; preserved stool received
Penicillium chrysogenum 602502 Synonyms Penicillium Notatum
Rapid Plasma Reagin (RPR), Qualitative Test 006072 Use This test can be used to follow treatment response in patients being treated for syphilis infection. This assay
should not be used to screen for syphilis infection. To screen for syphilis infection, a reflex cascade that includes
both RPR and a treponema-specfic assay should be utilized, such as Treponema pallidum (Syphilis) Screening
Cascade (082345) or Rapid Plasma Reagin (RPR) Test With Reflex to Quantitative RPR and Confirmatory Trepo-
nema pallidum Antibodies (012005).
Vancomycin, Serum, Trough 070328 Use Monitor therapeutic drug level
Methodology Immunoassay
Specimen Serum or plasma
Volume 1 mL
Minimum Volume 0.3 mL
Container Red-top tube or green-top (heparin) tube. Do not use a gel-barrier tube. The use of gel-barrier
tubes is not recommended due to slow absorption of the drug by the gel. Depending on the specimen volume
and storage time, the decrease in drug level due to absorption may be clinically significant.
Collection Transfer separated serum or plasma to a plastic transport tube. Trough concentrations should be
monitored. The trough sample is drawn immediately prior to the next dose.
Storage Instructions Refrigerate
Causes for Rejection Gel-barrier tube; hemolysis; lipemia; gross bacterial contamination
References
AMA Division of Drugs and Toxicology, Drug Evaluations Subscription, Chicago, IL: American Medical Associa-
tion, Spring 1990.
Brunton L, Lazo J, Parker K. Goodman & Gillman’s The Pharmacological Basis of Therapeutics. 11th ed. New York,
NY: McGraw-Hill, 2006.
Burtis CA, Ashwood CR, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. St Louis, MO:
Elsevier Saunders, 2006.
Dart RC, Caravati EM, McGuigan MA, et al. Medical Toxicology. Philadelphia, PA: Lippincott Williams & Wilkins,
2006.
Mosby’s Drug Consult. 17th ed. St Louis, MO: Elsevier Saunders, 2007.
Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic Monitoring of Vancomycin in Adult Patients: A consen-
sus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America,
and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009 Jan 1;(66)(1)82-98. PubMed
19106348

Note: Please consult the online Directory of Services and Interpretive Guide at https://www.labcorp.com/tests for the most current test information.

8
 Volume XVII, No. 11 LabHorizons November-December 2017
Test Name
Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor, Plasma
VistaSeqSM Brain/CNS/PNS Cancer Panel
VistaSeqSM High Risk Colorectal Cancer Panel
Vitamin B6, Plasma
Note: Please consult the online Directory of Services and Interpretive Guide at https://www.labcorp.com/tests for the most current test information.
Test No. Field/Change (Only fields that change are included here.)
117021 Limitations Results of this test are labeled for research purposes only by the assay’s manufacturer. The per-
formance characteristics of this assay have not been established by the manufacturer. The result should not
117006
be used for treatment or for diagnostic purposes without confirmation of the diagnosis by another medically
established diagnostic product or procedure. The performance characteristics were determined by LabCorp.
481386 Methodology The entire coding region of a panel of genes related to hereditary cancer is examined by next
generation sequencing analysis. Additionally, portions of the flanking noncoding regions are also examined.
Comprehensive deletion/ duplication testing is performed using microarray CGH for 16 genes, and by mul-
tiplex ligation-dependent probe amplification (MLPA) for the PMS2 gene. Genes tested in this panel include
ALK, APC, MEN1, MLH1, MSH2, MSH6, NBN, NF1, NF2, PHOX2B, PTCH1, PMS2, RB1, SMARCB1, SUFU, TP53, and VHL.
Clinically significant findings are confirmed by Sanger sequencing or qPCR. Results are reported using ACMG
guidelines and nomenclature recommended by the Human Genome Variation Society (HGVS).
481352 Methodology The entire coding region of a panel of genes related to hereditary cancer is examined by next
generation sequencing analysis. Additionally, portions of the flanking noncoding regions are also examined.
Comprehensive deletion/duplication testing is performed using microarray CGH for 6 genes, and by multiplex
ligation-dependent probe amplification (MLPA) for the PMS2 gene. Genes tested in this panel include APC,
EPCAM, MLH1, MSH2, MSH6, MUTYH and PMS2. Clinically significant findings are confirmed by Sanger sequenc-
ing or qPCR. Results are reported using ACMG guidelines and nomenclature recommended by the Human
Genome Variation Society (HGVS).
004655 Limitations This test was developed, and its performance characteristics determined, by LabCorp. It has not
been cleared or approved by the US Food and Drug Administration (FDA).
Methodology Liquid chromatography-tandem mass spectrometry (LC/MS-MS)
Additional Information Vitamin B6 occurs as an alcohol (pyridoxine), an aldehyde (pyridoxal), and an amine
(pyridoxamine). These forms are phosphorylated in the 5’-position to produce the physiologically active
coenzymes that are critical to their biological function. Eukaryotes cannot synthesize vitamin B6 molecules
from smaller compounds and as a result require dietary B6 for the synthesis of 5’-phosphate vitamins. Pyridoxal
5’Phosphate (PLP), the most clinically significant coenzyme form of vitamin B6, is the form most commonly
measured in plasma.1-3
PLP serves as a coenzyme for more than 100 enzymes that catalyze key steps in the metabolism of amino
acids, neurotransmitters, nucleic acids, heme, and lipids.1,4,5 Vitamin B6 is a critical cofactor for enzymes
involved in energy homeostasis through glycogen degradation and gluconeogenesis.5 Inverse associa-
tions have been shown between plasma PLP and chronic or acute disease, including rheumatoid arthritis,
cardiovascular disease, deep vein thrombosis, and cancer.4-16 A number of epidemiologic studies have shown
reduced concentrations of circulating PLP in association the acute phase marker C-reaction protein13-17 and
with inflammatory markers.18-19 Diminished vitamin B6 levels are frequently observed without any indication of
a lower dietary intake or excessive catabolism of the vitamin, or congenital defects in its metabolism.4 Research
is ongoing to determine if these lower vitamin B6 levels are caused by the mobilization of this coenzyme to the
site of inflammation for use by the PLP-dependent enzymes4 or due increased catabolism of vitamin B6 during
inflammation.5
PLP serves as a coenzyme for δ-aminolevulinate synthase, which catalyzes the first step in heme biosynthe-
sis.1,5 B6 deficiency can produce a hypochromic form of anemia characterized by the presence of ring sidero-
blasts (iron positive granules deposited about the nucleus of red cell precursors). Occasionally the anemia may
have megaloblastic characteristics. Inherited abnormalities of apoenzymes that bind with pyridoxal phosphate
are responsible for newborn conditions characterized by mental retardation, skeletal deformities, thrombotic
conditions, osteoporosis, and visual defects. Some inherited abnormalities of vitamin B6 metabolism and trans-
port are associated with aminoacidurias including homocystinuria, hypermethioninemia, cystathioninuria.21
A number of studies have demonstration an inverse association between plasma PLP levels and the risk of
developing colorectal cancer.20 A recent meta- analysis indicated that the risk of developing this type of cancer
decreased by 49% for every 100-pmol/mL increase in blood PLP level.20
Vitamin B6 deficiency can occur in individuals with a variety of genetic conditions including antiquitin defi-
ciency,21 pyridox(am)ine-5’-phosphate oxidase (PNPO) deficiency22 and hyperprolinemia type II (pyrroline-5-
carboxylate dehydrogenase deficiency.23 Vitamin B6 levels can be decreased in malabsorption conditions
including inflammatory disease of the small bowel and as a consequence of jejunoileal bypass.4,5 Several drugs,
including oral contraceptive agents, levodopa, isoniazid, cycloserine, and pyrazinoic acid may cause B6 deple-
tion.1 B6 levels may be decreased with pregnancy, lactation and alcoholism.1 Infants can develop deficiency
when fed formula rendered B6 depleted by excessive heating.
Markedly elevated plasma PLP levels are observed in cases of hypophosphatasia (HPP), an inborn error of
metabolism caused by a loss-of-function mutation(s) within the gene for the cell surface enzyme, tissue non-
specific isoenzyme of alkaline phosphatase (TNSALP).24-28 This disorder is characterized by low serum alkaline
phosphatase activity and increased plasma levels of TNSALP substrates including inorganic pyrophosphate,
phosphatidylethanolamine and PLP. Clinical features can include childhood rickets, adult osteomalacia and
dental abnormalities. These symptoms are thought to occur as a result of the accumulation of inorganic
pyrophosphate which inhibits hydroxyapatite crystal formation and growth, leading to defective skeletal and
dental mineralization. PLP, carried in the plasma on albumin, must be de-phosphorylated by TNSALP for pyri-
doxal to cross cell membranes. Once inside the cell, the pyridoxal is regenerated as PLP to allow it to function
as a coenzyme. The diminished TNSALP of individuals with HPP leads to an accumulation of the PLP substrate
in plasma. HPP patients do not typically experience B6 related symptoms. However, the extent of PLP elevation
has been related to the disease severity.28
Storage Instructions Refrigerate or freeze and protect from light.
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 Volume XVII, No. 11 LabHorizons November-December 2017

Test Name Test No. Field/Change (Only fields that change are included here.)
Vitamin B6, Plasma (continued) 004655 Specimen Plasma (EDTA), protected from light
Volume 0.5 mL
Minimum Volume 0.25 mL
Container Lavender-top (EDTA) tube; amber plastic transport tube with amber-top. (If amber tubes are unavail-
able, cover standard transport tube completely, top and bottom, with aluminum foil. Identify specimen with
patient’s name directly on the container and on the outside of the aluminum foil. Secure with tape.) For amber
plastic transport tube and amber-top, order LabCorp item No. 23594.
Collection Collect blood by venipuncture into a lavender-top tube containing EDTA and mixed immediately by
gentle inversion at least six times to ensure adequate mixing. The specimen must be separated and protected
from light in an amber transport tube with amber stopper. Specimens should be stored refrigerated or frozen
immediately and maintained at temperature during shipping and at the testing facility. To avoid delays in turn-
around time when requesting multiple tests on frozen samples, please submit separate frozen specimens
for each test requested.
Storage Instructions Refrigerate or freeze and protect from light.
Stability
Temperature Period
Room temperature 3 days
Refrigerated 15 days
Frozen 15 days
Freeze/thaw cycles Stable x6

Causes for Rejection Anticoagulants other than EDTA; specimen not protected from light
Footnotes
1. Food and Nutrition Board, Institute of Medicine. Vitamin B6. In: Dietary reference intakes for thiamin, ribofla-
vin, niacin, vitamin B6, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: National Academy
Press; 1998: 150-195. PubMed 23193625
2. Lamers Y. Indicators and methods for folate, vitamin B-12, and vitamin B-6 status assessment in humans.
Curr Opin Clin Nutr Metab Care. 2011 Sep;14(5):445-454. PubMed 21832901
3. Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5’-phosphate in the US population: the Na-
tional Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr. 2008 May;87(5):1446-1454. PubMed
18469270
4. Paul L, Ueland PM, Selhub J. Mechanistic perspective on the relationship between pyridoxal 5’-phosphate
and inflammation. Nutr Rev. 2013 Apr;71(4):239-244. PubMed 23550784
5. Ulvik A, Midttun O, Pedersen ER, Eussen SJ, Nygård O, Ueland PM. Evidence for increased catabolism of
vitamin B-6 during systemic inflammation. Am J Clin Nutr. 2014 Jul;100(1):250-255. PubMed 24808485
6. Roubenoff R, Roubenoff RA, Selhub J, et al. Abnormal vitamin B6 status in rheumatoid cachexia. Association
with spontaneous tumor necrosis factor alpha production and markers of inflammation. Arthritis Rheum. 1995
Jan; 38(1):105-109. PubMed 7818558
7. Dalery K, Lussier-Cacan S, Selhub J, Davignon J, Latour Y, Genest J Jr. Homocysteine and coronary artery dis-
ease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate, and folate. Am J Cardiol.
1995 Jun 1;75(16):1107-1111. PubMed 7762494
8. Saibeni S, Cattaneo M, Vecchi M, et al. Low vitamin B6 plasma levels, a risk factor for thrombosis in inflam-
matory bowel disease; role of inflammation and correlation with acute phase reactants low vitamin B6 levels
and IBD. Am J Gastroenterol. 2003 Jan; 98(1):112-117. PubMed 12526945
9. Cattaneo M, Lombardi R, Lecchi A, Bucciarelli P, Mannucci PM. Low plasma levels of vitamin B6 are indepen-
dently associated with a heightened risk of deep-vein thrombosis. Circulation. 2001 Nov 13;104(20):2442-2446.
PubMed 11705822
10. Le Marchand L, White KK, Nomura AM, et al. Plasma levels of B vitamins and colorectal cancer risk: the
multiethnic cohort study. Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2195-2201. PubMed 19661077
11. Wei EK, Giovannucci E, Selhub J, Fuchs CS, Hankinson SE, Ma J. Plasma vitamin B6 and the risk of colorectal
cancer and adenoma in women. J Natl Cancer Inst. 2005 May 4;97(9):684-692. PubMed 15870439
12. Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of
coronary heart disease among women. JAMA. 1998 Feb 4;279(5):359-364. PubMed 9459468
13. Shen J, Lai CQ, Mattei J, Ordovas JM, Tucker KL. Association of vitamin B-6 status with inflammation, oxida-
tive stress, and chronic inflammatory conditions: the Boston Puerto Rican Health Study. Am J Clin Nutr. 2010
Feb; 91(2):337-342. PubMed 19955400
14. Chiang EP, Bagley PJ, Selhub J, Nadeau M, Roubenoff R. Abnormal vitamin B(6) status is associated with
severity of symptoms in patients with rheumatoid arthritis. Am J Med. 2003 Mar;114(4):283-287. PubMed
12681455
15. Chiang EP, Smith DE, Selhub J, Dallal G, Wang YC, Roubenoff R. Inflammation causes tissue-specific deple-
tion of vitamin B6. Arthritis Res Ther. 2005;7(6):R1254-1262. PubMed 16277678
16. Friso S, Jacques PF, Wilson PW, Rosenberg IH, Selhub J. Low circulating vitamin B(6) is associated with
elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circula-
tion. 2001 Jun 12;103(23):2788-2791. PubMed 11401933
17. Ulvik A, Midttun O, Pedersen ER, Nygård O, Ueland PM. Association of plasma B-6 vitamers with systemic
markers of inflammation before and after pyridoxine treatment in patients with stable angina pectoris. Am J
Clin Nutr. 2012 May;95(5):1072-1078. PubMed 22492365
18. Sakakeeny L, Roubenoff R, Obin M, et al. Plasma pyridoxal-5-phosphate is inversely associated with
systemic markers of inflammation in a population of US adults. J Nutr. 2012 Jul;142(7):1280-1285. PubMed
22623384

Note: Please consult the online Directory of Services and Interpretive Guide at https://www.labcorp.com/tests for the most current test information.

10
 Volume XVII, No. 11 LabHorizons November-December 2017

Test Name Test No. Field/Change (Only fields that change are included here.)
Vitamin B6, Plasma (continued) 004655 19. Folsom AR, Desvarieux M, Nieto JF, Boland LL, Ballantyne CM, Chambless LE. B vitamin status and inflam-
matory markers. Atherosclerosis. 2003 Jul;169(1):169-174. PubMed 12860264
20. Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective stud-
ies. JAMA. 2010 Mar 17;303(11):1077-1083. PubMed 20233826
21. Mills PB, Struys E, Jakobs C, et al. Mutations in antiquitin in individuals with pyridoxine-dependent sei-
zures. Nat Med. 2006 Mar;12(3):307-309. PubMed 16491085
22. Mills PB, Surtees RA, Champion MP, et al. Neonatal epileptic encephalopathy caused by mutations in the
PNPO gene encoding pyridox(am)line 5#-phosphate oxidase. Hum Mol Genet. 2005 Apr 15;14(8):1077-1086.
PubMed 15772097
23. Walker V, Mills GA, Peters SA, Merton WL. Fits, pyridoxine, and hyperprolinaemia type II. Arch Dis Child. 2000
Mar;82(3):236-237. PubMed 10685929
24. Mornet E. Hypophosphatasia. Orphanet J Rare Dis. 2007 Oct 4;2:40. PubMed 17916236
25. Whyte MP, Mahuren JD, Vrabel LA, Coburn SP. Markedly increased circulating pyridoxal-5’-phosphate levels
in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism. J Clin Invest. 1985 Aug;76(2):752-
756. PubMed 4031070
26. Iqbal SJ, Brain A, Reynolds TM, Penny M, Holland S. Relationship between serum alkaline phosphatase
and and pyridoxal-5’-phosphate levels in hypophosphatasia. Clin Sci (Lond). 1998 Feb;94(2):203-206. PubMed
9536930
27. Berkseth KE, Tebben PJ, Drake MT, Hefferan TE, Jewison DE, Wermers RA. Clinical spectrum of hypophos-
phatasia diagnosed in adults. Bone. 2013 May;54(1):21-27. PubMed 23352924
28. Khandwala HM, Mumm S, Whyte MP. Low serum alkaline phosphatase activity and pathologic frac-
ture; case report and brief review of hypophosphatasia diagnosed in adulthood. Endocr Pract. 2006 Nov-
Dec;12(6):676-681. PubMed 17229666
References
Cabo R, Kozik K, Milanowski M, Hernes S, et al. A simple high-performance liquid chromatography (HPLC)
method for the measurement of pyridoxal-5-phosphate and 4-pyridoxic acid in human plasma. Clin Chim Acta.
2014 Jun 10; 433:150-156. PubMed 24657184
U.S. Centers for Disease Control and Prevention. Second national report on biochemical indicators of diet and
nutrition in the U.S. population 2012. Atlanta (GA): National Center for Environmental Health; April 2012. Avail-
able from: http://www.cdc.gov/nutritionreport.
Vitamin B12 001503 Reference Interval 232−1245 pg/mL

Note: Please consult the online Directory of Services and Interpretive Guide at https://www.labcorp.com/tests for the most current test information.

11
 Volume XVII, No. 11 LabHorizons November-December 2017

Deleted Procedures
Deleted Tests Test No. LabCorp Offers Test No.
Argatroban 117099 Please contact your LabCorp representative for testing options.

Influenza A, Real-time RT-PCR, H1N1 (Novel) 186205 Influenza A and B, Real-time RT-PCR 186221

Influenza A and B, Real-time RT-PCR With Reflex to Influenza A, H1N1

186270 Influenza A and B, Real-time RT-PCR 186221
(Novel)

Methyl Ethyl Ketone (MEK), Occupational Exposure, Urine 790770 Please contact your LabCorp representative for testing options.

Methyl Ethyl Ketone (MEK), Occupational Exposure, Whole Blood 790590 Please contact your LabCorp representative for testing options.

Methyl Isobutyl Ketone (MIK), Occupational Exposure, Whole Blood 790628 Please contact your LabCorp representative for testing options.

Methyl n-Butyl Ketone (MnBK), Occupational Exposure, Whole Blood 790618 Please contact your LabCorp representative for testing options.

n-Heptane, Occupational Exposure, Whole Blood 790630 Please contact your LabCorp representative for testing options.

n-Hexane, Occupational Exposure, Serum or Plasma 808008 Please contact your LabCorp representative for testing options.

Viral Culture, Rapid, Influenza A and Influenza B Virus 186023

Viral Culture, Rapid, Influenza A and Influenza B Virus With Reflex to
186239
Influenza A, H1N1 (Novel)
Influenza A and B, Real-time RT-PCR 186221

The CPT codes listed are in accordance with the current edition of Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided for the
convenience of our clients; however, correct coding often varies from one carrier to another. Consequently, the codes presented here are intended as general guidelines and should not
be used without confirming with the applicable payer that their use is appropriate in each case.

LOINC® Map. The Logical Observation Identifiers Names and Codes (LOINC®) corresponding to the individual LabCorp published assays is updated on a regular basis at www.labcorp.com.

©2017 Laboratory Corporation of America® Holdings All Rights Reserved. L17929-1217-1