TPMT Phenotype/Enzyme Activity




Test Mnemonic

PPRENZ

CPT Codes

  • 84433 - QTY (1)

LOINC ®

21563-2

Aliases

  • Thiopurine Methyltransferase, RBC

Performing Laboratory

ARUP

FDA Category

Laboratory Developed Test


Specimen Requirements

Volume Type Container Collect Temperature Transport Temperature Special Instructions
5 mLWhole bloodEDTA (Lavender) RefrigeratedCollect 2 separate EDTA tubes. Refrigerate ASAP.

Alternate Specimen Requirements

Volume Type Container Collect Temperature Transport Temperature Special Instructions
5 mLWhole bloodSodium or Lithium heparin (Green) RefrigeratedCollect 2 separate tubes. Do not use gel separator tubes. Refrigerate ASAP.

Minimum Specimen Requirements

Volume Type Container Collect Temperature Transport Temperature Special Instructions
3 mL     

Stability

Environmental Condition Description
Ambient3 hours
Refrigerated6 days
FrozenUnacceptable

Days Performed

Mon, Wed, Fri

Turnaround Time

4 - 6 days

Methodology

Name Description
Enzymatic 
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) 

Reference Range

TPMT Activity
Sex Age From Age To Type Range Range Unit
       Normal TPMT activity: 24.0-44.0 U/mL - Individuals are predicted to be at low risk of bone marrow toxicity (myelosuppression) as a consequence of standard thiopurine therapy; no dose adjustment is recommended 
       Intermediate TPMT activity: 17.0-23.9 U/mL - Individuals are predicted to be at intermediate risk of bone marrow toxicity (myelosuppression), as a consequence of standard thiopurine therapy; a dose reduction and therapeutic drug management is recommended 
       Low TPMT activity: < 17.0 U/mL - Individuals are predicted to be at high risk of bone marrow toxicity (myelosuppression) as a consequence of standard thiopurine dosing. It is recommended to avoid the use of thiopurine drugs 
       High TPMT activity: > 44.0 U/mL - Individuals are not predicted to be at risk for bone marrow toxicity (myelosuppression) as a consequence of standard thiopurine dosing, but may be at risk for therapeutic failure due to excessive inactivation of thiopurine drugs. Individuals may require higher than the normal standard dose. Therapeutic drug management is recommended 

Special Info

This assay measures only enzyme activity. Gel separator tubes and specimens collected in sodium fluoride/potassium oxalate tubes (gray) are unacceptable. Hemolyzed, frozen, or room temperature specimens are not acceptable. This test is New York DOH approved.

Clinical Info

Phenotype test to assess risk for severe myelosuppression with standard dosing of thiopurine drugs. Use for individuals being considered for thiopurine therapy. Must be performed before thiopurine therapy is initiated. Can also detect rapid metabolizer phenotype. The TPMT, RBC assay is used as a screen to detect individuals with low and intermediate TPMT activity who may be at risk for myelosuppression when exposed to standard doses of thiopurines, including azathioprine (Imuran) and 6-mercaptopurine (Purinethol). 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. The activity of TPMT is measured by the nanomoles of 6-methylmercaptopurine (inactive metabolite) produced per 1 mL of packed red blood cells, (U/mL). 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. Current TPMT phenotype may not reflect future TPMT phenotype, particularly in patients who received blood transfusion within 30-60 days of testing. TPMT enzyme activity can be inhibited by several drugs such as: naproxen (Aleve), ibuprofen (Advil, Motrin), ketoprofen (Orudis), furosemide (Lasix), sulfasalazine (Azulfidine), mesalamine (Asacol), olsalazine (Dipentum), mefenamic acid (Ponstel), thiazide diuretics, and benzoic acid inhibitors. TPMT inhibitors may contribute to falsely low results; patients should abstain from these drugs for at least 48 hours prior to TPMT testing. Falsely low results may also occur as a result of inappropriate specimen handling and hemolysis.