Thiopurine Methyltransferase
Label Mnemonic: TPMTRBC
Epic Lab Code: LAB4153
Downtime Form: A-1a Miscellaneous Request
Commercial Mail-out Laboratory
5231 RCP
356-8593
Specimen(s):
Whole Blood
Collection Medium:
Pink top tube 6 mL (K2-EDTA)
Minimum:
Preferred Minimum: 5 mL whole blood
Absolute Minimum: 3 mL whole blood
Rejection Criteria:
Specimens collected in sodium fluoride/potassium oxalate (gray). Hemolyzed, frozen, or room temperature specimens.
Turn Around Time:
3-4 days upon receipt at reference laboratory.
Reference Range:
Normal TPMT activity: 25-65 U/mL - Individuals are predicted to be at low risk of bone marrow toxicity as a consequence of standard thiopurine therapy; no dose adjustment is recommended.

Abnormal TPMT activity: < 25 U/mL - Individuals are predicted to be at high risk of bone marrow toxicity as a consequence of standard thiopurine dosing; a dose reduction and therapeutic monitoring is recommended.

High TPMT activity: > 65 U/mL - Individuals are not predicted to be at low risk for bone marrow toxicity 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 standard dose; therapeutic monitoring is recommended.
Interpretive Data:
The TPMT, RBC assay is used as a screen to detect individuals with low (abnormal) TPMT activity that may be at risk for excessive myelosuppression when exposed to standard doses of thiopurines such as 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 is converted into the cytotoxic 6- thioguanine nucleotides, which will accumulate in the bone marrow and cause 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, as results will be falsely low. 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.

NOTE: This assay only measures enzyme activity.
Methodology:
Enzymatic/Quantitative Liquid Chromatography-Tandem Mass Spectrometry
CPT Code:
82657