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 cannot achieve therapeutic levels as they have therapeutic resistance to thiopurine drugs. Severe hepatotoxicity may develop if an individual with TPMT hyperactivity is treated with higher and higher doses of thiopurine drugs.

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.

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