The detection of patients who are at risk of developing severe side effects if treated with the thiopurine drugs, azathioprine, mercaptopurine and thioguanine
Prior to thiopurine drug treatment
A single blood sample taken from a vein in your arm
There are no special preparations needed to collect the blood.
Before taking a sample for TPMT activity, patients may be advised that DNA confirmation may be performed. The only known implication for the genetic variation in TPMT expression is intolerance to thiopurine drugs.
Thiopurine drugs suppress the immune system and are used to treat autoimmune and inflammatory diseases and to prevent patients rejecting organ transplants. They are also used in the treatment of leukaemia and skin disorders such as eczema. The most commonly used thiopurine drug is called azathioprine.
Approximately 0.3% of the population lack thiopurine s-methyltransferase (TPMT), an enzyme which helps remove thiopurine drugs such as azathioprine from the body. In addition approximately 11% of the population have measurable but reduced levels of TPMT (so called intermediate group). Individuals with no TPMT activity can become severely ill if treated with normal doses of thiopurine drugs. These patients develop bone marrow suppression with a reduction in blood cells, which causes anaemia, infection and abnormal bleeding. Patients from the intermediate group of TPMT deficiency may in some cases have less marked effects. Such side effects can be avoided if TPMT is measured before starting treatment.
How is it used?
TPMT is measured in patients who are about to start treatment with thiopurine drugs such as azathioprine. TPMT activity varies in the population and this means that different people require different doses of thiopurine drugs to get the desired therapeutic effects. Guidance in the UK recommends that patients commencing thiopurine drugs have their TPMT status checked before treatment begins. The test identifies individuals at risk of developing severe side effects such as lowering of blood cell counts and a lowered immune response.
When is it requested?
What does the test result mean?
If a patient has no detectable TPMT activity then they are at risk of developing severe side effects to thiopurine drugs. Usually the doctor will find an alternative drug treatment. A low TPMT activity is still compatible with thiopurine drug treatment but a lower dose is indicated.
If a patient has normal TPMT activity then the doctor can treat the patient with a standard dose of a thiopurine drug.
Is there anything else I should know?
The 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. The underlying basis to the variation is genetic differences in the population and when patients with no TPMT activity are identified their DNA (for TPMT genotyping) is usually studied as well to confirm this status.
Globally the other genetic variation that can result azathioprine toxicity is in NUDT15 gene. This test has recently become available for people with acute lymphoblastic leukaemia about to receive azathioprine but hopefully will become more widely available in the future.
What does TPMT normally do in the body?
No one really knows the answer to this. The enzyme is found in many cells but the interest in TPMT is purely in looking at patients who are to receive thiopurine drugs as this enzyme breaks down these drugs to inactive metabolites. Around 1 in 300 people have no TPMT activity and a further 11% have low activity.