Test Id : TPMT3
Thiopurine Methyltransferase Activity Profile, Erythrocytes
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.
For more information see:
-Ulcerative Colitis and Crohn Disease Therapeutic Drug Monitoring Algorithm
-TPMT Testing in the Treatment of Inflammatory Bowel Disease Algorithm
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.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
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.
For more information see:
-Ulcerative Colitis and Crohn Disease Therapeutic Drug Monitoring Algorithm
-TPMT Testing in the Treatment of Inflammatory Bowel Disease Algorithm
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 non-centrifuged plasma gel tubes
Specimen Volume: 5 mL
Collection Instructions: Send whole blood specimen. Do not centrifuge.
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)
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 | Refrigerated (preferred) | 6 days | |
| Ambient | 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.
For more information see:
-Ulcerative Colitis and Crohn Disease Therapeutic Drug Monitoring Algorithm
-TPMT Testing in the Treatment of Inflammatory Bowel Disease Algorithm
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.
Thiopurine methyltransferase deficiency is inherited as a codominant trait, and variable TPMT activity is associated with TPMT genetic variants. The distribution of TPMT activity in red blood cells is trimodal in the population of people with European ancestry, with approximately 0.3% having deficient (undetectable) TPMT activity, 11% low (intermediate) activity, and 89% normal TPMT activity.. Adverse effects of AZA, 6-MP, or 6-TG administration can be observed in individuals with severe or intermediate TPMT deficiency.
Thiopurine methyltransferase 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/h
6-Methylmercaptopurine riboside (normal): 5.04-9.57 nmol/mL/h
6-Methylthioguanine riboside (normal): 2.70-5.84 nmol/mL/h
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 a suggestion as to whether patient has TPMT deficiency or hyperactivity, as well as discussion of treatment considerations.
Thiopurine methyltransferase 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.
Thiopurine methyltransferase 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.
Several drugs can inhibit thiopurine methyltransferase (TPMT) enzyme activity and may cause falsely low results, including 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.
Patients with acute lymphoblastic leukemia may have lower TPMT activities before treatment and higher activities following treatment.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. TPMT nomenclature committee (TPMT Alleles): Table of TPMT Alleles. Linkoping University; Updated November 2022. Accessed July 15, 2025. Available at https://liu.se/en/research/tpmt-nomenclature-committee
2. 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
3. Lennard L. Implementation of TPMT testing. Br J Clin Pharmacol. 2014;77(4):704-714
4. 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
5. Zhou S. Clinical pharmacogenomics of thiopurine S-methyltransferase. Curr Clin Pharmacol. 2006;1(1):119-128
6. 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
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
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.
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 |