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To detect a thiopurine methyltransferase (TPMT) deficiency and determine your risk of developing severe side effects if treated with the class of immune-suppressing thiopurine drugs that includes azathioprine, mercaptopurine, and thioguanine
Typically, prior to thiopurine drug treatment; this is a specialized test and is not routinely ordered.
A blood sample drawn from a vein in your arm or a swab from inside your cheek (i.e., buccal swab)
For measuring TPMT enzyme activity (TPMT phenotyping), the test must be performed prior to taking a thiopurine drug since it may affect results; for the genetic test (TPMT genotyping), no specific test preparation is needed.
Thiopurine methyltransferase (TPMT) is an enzyme that breaks down (metabolizes) a class of drugs called thiopurines. These drugs are used to suppress the immune system and are prescribed to treat various immune-related conditions or blood disorders (e.g., leukemia). The activity level of the TPMT enzyme, or the genetics underlying the enzyme's activity, is tested before thiopurine drug therapy to make sure that individuals treated with the drugs can metabolize them.
Examples of thiopurines include azathioprine, mercaptopurine, and thioguanine. These medications are used to treat diseases such as acute lymphoblastic leukemia, inflammatory bowel disease, and autoimmune disorders. They may also be prescribed for organ transplant recipients to help delay or prevent organ rejection. If someone's TPMT activity is too low, the person may not effectively metabolize thiopurines, which can lead to severe side effects.
About one person in every 300 is severely deficient in TPMT, and about 10% of the population in the U.S. has lower than normal levels of TPMT. Individuals in both categories are at an increased risk for thiopurine drug toxicity, which can affect the activity of the bone marrow (myelosuppression) and lead to very reduced levels of blood cells, such as red blood cells, white blood cells and platelets (hematopoetic toxicity). This can lead to complications such as anemia, serious infections, and/or excessive bleeding.
These side effects can cause an individual to become severely ill and may even be life-threatening. These side effects can be avoided if TPMT testing is done before starting thiopurine treatment.
There are two ways to determine whether an individual is at risk of side effects from thiopurine therapy:
This genetic test provides information about a person's likely response to thiopurines, but it will not measure how much TPMT enzyme is actually being made by the body. There can be significant person-to-person and ethnic variability in TPMT production, even in people with the same gene variations.
A third, different kind of test may be used after thiopurine treatment begins. A test that measures thiopurine breakdown products (thiopurine metabolites) may be used to monitor therapy and adjust doses. For more on this, see Common Questions below.
For both genetic and enzyme activity testing, a blood sample is taken by needle from a vein in the arm. Alternatively, for the genetic test alone, a swab of cells from the inside cheek (buccal swab) may be collected.
For the method that measures TPMT enzyme activity, taking a thiopurine drug could lead to falsely low results, so the test should be performed prior to starting therapy. For the genetic test (TPMT genotyping), no specific test preparation is needed.
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, such as suppression of the bone marrow that leads to reduced numbers of red blood cells, white blood cells and platelets.
Thiopurines such as azathioprine, mercaptopurine, and thioguanine are drugs that are prescribed for diseases such as acute lymphoblastic leukemia (ALL), inflammatory bowel disease, and autoimmune disorders. They may also be prescribed for organ transplant recipients to help prevent organ rejection.
A healthcare practitioner 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.
Phenotype test for TPMT
Genotype test for TPMT
Though the TPMT test is used to predict risk of bone marrow toxicity, complete blood counts (CBCs) should also be done at regular intervals to detect bone marrow toxicity during treatment with thiopurine drugs. The CBC is a common blood test that measures the number of red blood cells, white blood cells and platelets. It is often used to monitor drug treatments that are known to affect the bone marrow.
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.
A few people may have high levels of TPMT activity. It is thought that this decreases the effectiveness of thiopurine therapy, and these people may be treated with an alternative drug.
A healthcare practitioner may order a blood test for thiopurine metabolites to monitor drug therapy. Measuring the metabolites is another way to ensure that toxic levels do not build up in the blood. Prior to administering the first dose, a healthcare practitioner may test a person's TPMT enzyme activity or genotype to help determine risk of side effects as described in other sections of this article. The healthcare practitioner can adjust the prescribed dose according to those results. After therapy begins, the level of metabolites can be measured and monitored, with subsequent doses adjusted as necessary to avoid toxicity.
The opinions of medical organizations vary on which TPMT test to recommend. You should consult with your healthcare practitioner about which one best fits your individual situation. For example:
Sources Used in Current Review
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Sources Used in Previous Reviews
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