Thiopurine Methyltransferase Activity (Sendout)

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General Information

Lab Name
Thiopurine Methyltransferase Activity (Sendout)
Lab Code
RTPMTA
Epic Ordering
Thiopurine Methyltransferase Activity (Sendout)
External Test Id
TPMT3
Description

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

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.

Synonyms
Azathioprine toxicity, Hematopoietic toxicity, Imuran toxicity, Mercaptopurine (6-MP) toxicity, Myelosuppression, Purinethol toxicity, RTMTG, Thioguanine (6-TG) toxicity, Thiopurine resistance, TPMT (Thiopurine Methyltransferase), TPMT enzyme, TPMT Phenotype, TPMT3
Components

Interpretation

Method

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

Reference Range
See individual components
Ref. Range Notes

Reference Values:

6-Methylmercaptopurine: 3.00-6.66 nmol/mL/hour
6-Methylmercaptopurine riboside: 5.04-9.57 nmol/mL/hour
6-Methylthioguanine riboside: 2.70-5.84 nmol/mL/hour

Interpretation:

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 have therapeutic resistance to thiopurine drugs, and therefore they 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.

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.

Interferences and Limitations

Cautions:

Falsely low results may occur as a result of inappropriate specimen handling and hemolysis.

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

TPMT activity is measured in red blood cells. If a patient has had a blood transfusion within 30 to 60 days of testing, the patient's true enzyme activity may not be accurately reflected.

Ordering & Collection

Specimen Type
Blood
Collection

Collect 6 mL blood in LAVENDER TOP (EDTA) tube

Also accepted: Green top tubes (sodium or lithium heparin), navy blue top (metal free sodium heparin), or green PST (unspun)

Handling Instructions

Outside Laboratories: Refrigerate whole blood. Expedite transport to UW-MT to ensure that samples arrive within stability, allowing for additional transport time to Mayo.

Stability: Refrigerated (preferred): 6 days; Ambient: 6 days; Frozen: Unacceptable.

Reject Due To: Gross hemolysis.

Quantity
requested: 6 mL EDTA whole blood
minimum: 3 mL EDTA whole blood

Processing

Processing

Refrigerate whole blood in original collection container.

Sendouts:

  • Order Mayo Test: TPMT3.
  • Interfaced: Yes.
  • Specimens must arrive at Mayo within 6 days of collection.

Stability: Refrigerated (preferred): 6 days; Ambient: 6 days; Frozen: Unacceptable.

Reject Due To: Gross hemolysis.

Performance

LIS Dept Code
Sendouts Mayo Lab (RF) (MARF)
Performing Location(s)
Sendout Mayo Clinic Laboratories
800-533-1710

200 First Street Southwest
Rochester, MN 55901

Frequency
Performed: Monday, Wednesday, Friday. Report Available: 3-6 days.
Available STAT?
No

Billing & Coding

CPT codes
84433
LOINC
91139-6
Interfaced Order Code
UOW4683