Phenotype test to assess risk for severe myelosuppression with standard dosing of thiopurine drugs. Testing should be performed prior to initiation of thiopurine therapy. For therapy optimization or toxicity evaluation, order Thiopurine Metabolites by LC-MS/MS (2014484).
Enzymatic/Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Lavender (EDTA), pink (K2EDTA), or green (sodium or lithium heparin).
Transport 5 mL whole blood. (Min: 3 mL)
Gel separator tubes. Specimens collected in sodium fluoride/potassium oxalate (gray). Hemolyzed, frozen, or room temperature specimens.
Ambient: 3 hours; Refrigerated: 6 days; Frozen: Unacceptable
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.
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.
Laboratory Developed Test (LDT)
This assay measures only enzyme activity.
|Component Test Code*||Component Chart Name||LOINC|
- 6 mercaptopurine
- TPMT Enzyme
- TPMT Erythrocytes