At a Glance
Why Get Tested?
To detect patients who are at risk of developing severe side effects if treated with the class of thiopurine drugs that includes azathioprine, mercaptopurine, and thioguanine
When to Get Tested?
Prior to thiopurine drug treatment
Sample Required?
A blood sample drawn from a vein in your arm
Test Preparation Needed?
None
The Test Sample
What is being tested?
Thiopurines are a class of drugs that suppress the immune system. Examples 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 to patients who have had organ transplants to help delay or prevent organ rejection. This test detects the activity level of the enzyme thiopurine S-methyltransferase (TPMT) in a person’s red blood cells. The activity level of TPMT is associated with the ability to effectively metabolize thiopurines.
Thiopurines must be activated and then inactivated in the body. TPMT is one of the crucial components of deactivation. If there is not a sufficient amount of TPMT present, then toxic active drug compounds can accumulate in the blood. About one person in every 300 is severely deficient in TPMT, and about 10% of the population has lower than normal levels. Individuals with intermediate amounts of TMPT are at an increased risk for drug toxicity. Those with little to no TPMT enzyme can develop suppression of their bone marrow (myelosuppression) and become severely ill if treated with normal doses of thiopurine drugs. This suppression leads to a reduction in the production of red and white blood cells, which in turn can cause infection and abnormal bleeding. Such side effects can be avoided if TPMT is measured before starting treatment.
TPMT activity levels can be affected by variations (mutations) in the genes that code for the production of TPMT. There is a one-time genetic test that can be done on the DNA of an individual. Tests typically detect the most common gene mutations, but do not test for all of them and will not account for TPMT gene variations that have not yet been identified. This test can give a doctor information about her patient’s likely response to thiopurines, but it will not quantify how much TPMT is actually being made by the body. There can be significant person-to-person and ethnic variability in TPMT production, even when people have the same gene variations. When it is ordered, this genetic test is usually performed prior to thiopurine therapy. However, it is not affected by thiopurine therapy and can be performed at any time.
How is the sample collected for testing?
A blood sample is taken by a needle from a vein in your arm.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
The Test
How is it used?
TPMT is measured in patients who are about to start treatment with a thiopurine drug. The test identifies individuals at risk of developing severe side effects, such as lowering of blood cell counts.
When is it ordered?
A doctor may order a blood TPMT test before starting a patient on thiopurine drug treatment.
What does the test result mean?
If a patient 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 blood TPMT activity also puts the patient at increased risk for toxicity. In this case, the doctor may reduce the dose of thiopurine drug given.
If a patient has normal blood TPMT activity, the doctor can treat the patient with a standard dose of a thiopurine drug.
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.
Is there anything else I should know?
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.
Taking a thiopurine drug will affect the results of a TMPT test measuring enzyme activity, so the test should be performed prior to starting therapy.
The quantity of TPMT produced is governed by the two copies of TPMT gene that each person has. There are about a dozen different variations of the TPMT gene, but most people have two copies of a normal “wild type” TPMT gene that produces sufficient TPMT. People who produce an intermediate amount of TPMT may have one normal gene and one gene variation associated with decreased TPMT (heterozygous). Those who produce little to no TPMT typically have two copies of abnormal TPMT genes – either the same variation or two different ones. Of more than a dozen identified TPMT gene variations, three are associated with up to 95% of TPMT deficiencies.
Common Questions
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Related Pages
On This Site
Conditions: Inflammatory Bowel Disease, Autoimmune Disorders, Leukemia
Features: Pharmacogenomics
Elsewhere On The Web
Article Sources
NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Sources Used in Current Review
Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry, AACC Press, Washington, DC. Pp. 479.
Wu, A. (2006). Tietz Clinical Guide to Laboratory Tests, Fourth Edition. Saunders Elsevier, St. Louis, Missouri. Pp. 1420.
(2008 July). Thiopurine Methyltransferase, Red Blood Cell. ARUP Laboratories Technical Bulletin [On-line information]. PDF available for download at http://www.aruplab.com/Testing-Information/resources/TechnicalBulletins/Thiopurine%20Methyltransferase,%20Red%20Blood%20Cell.pdf through http://www.aruplab.com. Accessed on 1/4/09.
Ansari, A.et. al (2008 December 17). Prospective Evaluation of the Pharmacogenetics of Azathioprine in the Treatment of Inflammatory Bowel Disease. [On-line information]. Available online at http://www.medscape.com/viewarticle/584257 through http://www.medscape.com. Accessed on 1/4/09.
Aberra, F. and Lichtenstein, G. (Review Article: Monitoring of Immunomodulators in Inflammatory Bowel Disease. Medscape from Aliment Pharmacol Ther. 2005; 21 (4): 307-319. [On-line information]. Available online at http://www.medscape.com/viewarticle/499922_1 through http://www.medscape.com. Accessed on 1/4/09.
Derijks, L. et. al. (2006 September 26). Thiopurines in Inflammatory Bowel Disease. [On-line information]. Available online at http://www.medscape.com/viewarticle/543562 through http://www.medscape.com. Accessed on 1/4/09.
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER and Bruns DE, eds. 4th ed. St. Louis, Missouri: Elsevier Saunders; 2006, P. 1273.
Sources Used in Previous Reviews
Dr. Jonathon Berg. City Hospital, Birmingham, England.
