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HelpTEST ID TPMT3 Thiopurine Methyltransferase Activity Profile, Erythrocytes
Reporting Name
TPMT Activity Profile, RBCSpecimen Type
Whole bloodSpecimen Required
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.
Specimen Minimum Volume
3 mL
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole blood | Refrigerated (preferred) | 6 days |
| Ambient | 6 days |
Special Instructions
Testing Algorithm
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
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Reject Due To
| Gross hemolysis | Reject |
Reference Values
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
Day(s) Performed
Monday, Wednesday, Friday
Report Available
4 to 7 daysSpecimen Retention Time
Residual whole blood: 14 days; Processed specimen: 2 monthsPerforming Laboratory
Mayo Clinic Laboratories in Rochester
CPT Code Information
84433
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 1 of the following forms with the specimen:
Useful For
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.
Clinical Information
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.