Test Catalog

Test Id : TPMT3

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Thiopurine Methyltransferase Activity Profile, Erythrocytes

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Detection of individuals with low thiopurine methyltransferase (TPMT) activity who are at risk for excessive myelosuppression or severe hematopoietic toxicity when taking thiopurine drugs

 

Detection of individuals with hyperactive TPMT activity who have therapeutic resistance to thiopurine drugs and may develop hepatotoxicity if treated with these drugs

Highlights

Individuals who are either homozygous or heterozygous for thiopurine methyltransferase (TPMT) deficiency are at risk of developing life-threatening myelosuppression or severe hematopoietic toxicity when placed on standard doses of azathioprine (Imuran), 6-mercaptopurine (Purinethol), or 6-thioguanine (Thioguanine Tabloid).

 

Individuals who have TPMT hyperactivity cannot achieve therapeutic levels with thiopurine drugs, and they may develop hepatotoxicity due to treatment with thiopurine drugs.

 

Determining a patient's TPMT status prior to starting therapy with a thiopurine drug is, therefore, important for purposes of calculating the optimal drug dosage.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Method Name
A short description of the method used to perform the test

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

TPMT Activity Profile, RBC

Aliases
Lists additional common names for a test, as an aid in searching

Azathioprine toxicity

Imuran toxicity

Mercaptopurine (6-MP) toxicity

Purinethol toxicity

Thioguanine (6-TG) toxicity

Thiopurine resistance

Myelosuppression

Hematopoietic toxicity

TPMT (Thiopurine Methyltransferase)

TPMT Phenotype

Liver toxicity

TPMT enzyme

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Specimen Type
Describes the specimen type validated for testing

Whole blood

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: Thiopurine methyltransferase (TPMT) enzyme activity can be inhibited by several drugs and may contribute to falsely low results. Patients should abstain from the following drugs for at least 48 hours prior to TPMT testing: naproxen (Aleve), ibuprofen (Advil, Motrin), ketoprofen (Orudis), furosemide (Lasix), sulfasalazine (Azulfidine), mesalamine (Asacol), olsalazine (Dipentum), mefenamic acid (Ponstel), trimethoprim (Proloprim), methotrexate, thiazide diuretics, and benzoic acid inhibitors.

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Green top (sodium or lithium heparin), dark blue top (metal free sodium heparin), or plasma gel tubes

Specimen Volume: 5 mL

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send Gastroenterology and Hepatology Test Request (T728) with the specimen

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

3 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Whole blood Ambient 6 days
Refrigerated (preferred) 6 days

Useful For
Suggests clinical disorders or settings where the test may be helpful

Detection of individuals with low thiopurine methyltransferase (TPMT) activity who are at risk for excessive myelosuppression or severe hematopoietic toxicity when taking thiopurine drugs

 

Detection of individuals with hyperactive TPMT activity who have therapeutic resistance to thiopurine drugs and may develop hepatotoxicity if treated with these drugs

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Thiopurine methyltransferase (TPMT) deficiency is a condition in which patients treated with standard doses of azathioprine (AZA, Imuran), 6-mercaptopurine (6-MP, Purinethol), or 6-thioguanine (6-TG, Thioguanine Tabloid) may develop life-threatening myelosuppression or severe hematopoietic toxicity. The metabolic conversion of AZA, 6-MP, or 6-TG to purine nucleotides and the subsequent incorporation of these nucleotides into DNA play an important role in both the therapeutic efficacy and toxicity of these drugs. A competitive catabolic route for the metabolism of thiopurines is catalyzed by the TPMT enzyme, which inactivates them by thiomethylation. A balance must be established between these competing metabolic pathways so that sufficient amounts of drug are converted to the nucleotide to act as an antimetabolite and antimetabolite levels do not become so high as to cause potentially lethal bone marrow suppression.

 

TPMT deficiency is an autosomal recessive condition with an incidence of approximately 1 in 300 individuals homozygous for deleterious variants in the TPMT gene; about 10% of the population are heterozygous carriers of TPMT variants. Adverse effects of AZA, 6-MP, or 6-TG administration can be observed in individuals who are either homozygous or heterozygous for TPMT deficiency.

 

TPMT hyperactivity is also a known phenotype. Individuals who are hypermetabolizers have therapeutic resistance to thiopurine drugs and therefore, cannot achieve therapeutic levels. If an individual with TPMT hyperactivity is treated with higher and higher doses of thiopurine drugs, they may develop severe hepatotoxicity. Therefore, treatment with alternative medications is recommended for hypermetabolizers.

 

As such, knowing a patient's TPMT status prior to treatment with AZA, 6-MP, or 6-TG is important for purposes of calculating safe drug dosages for therapy.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

6-Methylmercaptopurine (normal): 3.00-6.66 nmol/mL/hour

6-Methylmercaptopurine riboside (normal): 5.04-9.57 nmol/mL/hour

6-Methylthioguanine riboside (normal): 2.70-5.84 nmol/mL/hour

Interpretation
Provides information to assist in interpretation of the test results

This assay is used to detect individuals with low and intermediate thiopurine methyltransferase (TPMT) activity who may be at risk for myelosuppression when exposed to standard doses of thiopurines, including azathioprine (Imuran), 6-mercaptopurine (Purinethol), or 6-thioguanine (Thioguanine Tabloid). TPMT is the primary metabolic route for inactivation of thiopurine drugs in the bone marrow. When TPMT activity is low, it is predicted that proportionately more 6-mercaptopurine can be converted into the cytotoxic 6-thioguanine nucleotides that accumulate in the bone marrow causing excessive toxicity.

 

This test can also detect TMPT hyperactivity. Individuals who are hypermetabolizers cannot achieve therapeutic levels as they have therapeutic resistance to thiopurine drugs. Severe hepatotoxicity may develop if an individual with TPMT hyperactivity is treated with higher and higher doses of thiopurine drugs.

 

The activity of TPMT is measured by 3 different substrates. Reports include the quantitative activity level of TPMT for each of 3 different substrates and an interpretation of these results. When abnormal results are detected, a detailed interpretation is given, including an overview of results and suggestion as to whether patient has TPMT deficiency or hyperactivity, as well as discussion of treatment considerations.

 

TPMT phenotype testing does not replace the need for clinical monitoring of patients treated with thiopurine drugs. Genotype for TPMT cannot be inferred from TPMT activity (phenotype). Phenotype testing should not be requested for patients currently treated with thiopurine drugs.

 

TPMT activity is measured in red blood cells. If a patient has had a blood transfusion within 60 days of testing, the patient's true enzyme activity may not be accurately reflected.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Falsely low results may occur due to inappropriate specimen handling or hemolysis.

 

Patients with acute lymphoblastic leukemia may have lower thiopurine methyltransferase activities before treatment and higher activities following treatment.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Relling MV, Gardner EE, Sandborn WJ, et al. Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther. 2011;89(3):387-391

2. Lennard L. Implementation of TPMT testing. Br J Clin Pharmacol. 2014;77(4):704-714

3. Schedel J, Godde A, Schutz E, et al. Impact of thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations in patients with chronic inflammatory diseases. Ann N Y Acad Sci. 2006;1069:477-491

4. Zhou S. Clinical pharmacogenomics of thiopurine S-methyltransferase. Curr Clin Pharmacol. 2006;1(1):119-128

5. Asadov C, Aliyeva G, Mustafayeva K. Thiopurine S-methyltransferase as a pharmacogenetic biomarker: Significance of testing and review of major methods. Cardiovasc Hematol Agents Med Chem. 2017;15(1):23-30

Method Description
Describes how the test is performed and provides a method-specific reference

Red blood cell lysate is incubated in a multi-substrate cocktail. The enzymatically generated thiomethylated products are measured by liquid chromatography tandem mass spectrometry to produce an activity profile for thiopurine methyltransferase.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Wednesday, Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

4 to 7 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Residual whole blood: 14 days; Processed specimen: 2 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees :
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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

84433

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
TPMT3 TPMT Activity Profile, RBC 91139-6
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
48038 Interpretation 59462-2
48034 6-Methylmercaptopurine 91141-2
48035 6-Methylmercaptopurine riboside 91142-0
48036 6-Methylthioguanine riboside 91143-8
48037 Reviewed By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports