The tests for thiopurine methyltransferase (TPMT) enzyme activity or its underlying genetics are measured in people who are about to start treatment with a thiopurine drug. One or the other of these tests is used to identify individuals at risk of developing severe side effects from thiopurine therapy.
People who have low enzyme activity have an increased risk of side effects, and those who are severely deficient are likely to experience serious side effects such as suppression of the bone marrow. When the bone marrow is suppressed, it is unable to produce sufficient numbers of red blood cells, white blood cells, and platelets. This may result in a significant drop in blood cell counts, leading to complications such as anemia, serious infections, and/or excessive bleeding. These complications may be life-threatening.
A doctor will typically order a TPMT enzyme activity test or genetic test before starting a person on thiopurine drug treatment. Occasionally, a TPMT genotype test may be ordered when a person treated with a thiopurine drug experiences side effects, such as a decreased WBC count.
If someone has little to no detectable TPMT activity, they are at risk of developing severe side effects to thiopurine drugs. Usually the doctor will find an alternative drug treatment. Sometimes the doctor may prescribe a very small dose of the thiopurine.
Low to intermediate TPMT activity also puts individuals at increased risk for toxicity. In this case, the doctor may reduce the dose of thiopurine drug given.
If someone has normal TPMT activity, the doctor can treat the person with a standard dose of a thiopurine drug.
Genotype test for TPMT
A genetic test to detect genetic variations in the TPMTgene will help determine TPMT activity and risk for side effects from low TPMT activity.
Individuals with two "wild type" copies of the TPMT gene produce sufficient TPMT and have little risk of thiopurine toxicity. Most people fall into this category and can be treated with a standard dose.
People who have one normal gene and one gene variation associated with decreased TPMT (heterozygous) may produce an intermediate amount of TPMT. Approximately 30-60% of people who are heterozygous have severe side effects from standard doses of thiopurines. They will likely require reduced doses of the drug but may need to be given an alternative drug.
People with two copies of a variant TPMT gene (homozygous) and who produce little to no TPMT have 100% likelihood of developing severe bone marrow toxicity (myelosuppression) when treated with conventional doses of thiopurines. They will likely be given an alternative drug.
The genetic test usually detects the most common variants associated with TPMT deficiency. It is possible for a person to have a rare variant not detected by this test, who may subsequently experience serious side effects from treatment with a thiopurine drug.
TPMT enzyme activity is measured in red blood cells, so if you have recently received a transfusion of blood, the results of this test may be inaccurate.
Besides your genetic makeup, there may be other reasons for increased risk of bone marrow toxicity (myelosuppression) from treatment with thiopurine drugs. Interactions between certain drugs can also inhibit TPMT enzyme activity. These drugs include naproxen, ibuprofen, ketoprofen, furosemide, sulfasalazine, mesalamine, olsalazine, mefenamic acid, thiazide diuretics, and benzoic acid inhibitors. TPMT inhibitors may contribute to falsely low results; people should not take these drugs for at least 48 hours prior to TPMT testing.
While the TPMT genotype test may predict risk of myelosuppression, the test should not replace complete blood count (CBC) monitoring to detect myelosuppression during treatment with thiopurine drugs. CBC monitoring is a common test and is sometimes ordered as a routine part of monitoring drug treatments, including those that affect bone marrow.
A few people may have high levels of TPMT activity. It is thought that this decreases the effectiveness of thiopurine therapy, but there is not yet consensus on how this information should be used to guide treatment.
This article was last reviewed on May 28, 2013. | This article was last modified on May 29, 2013.
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