What causes low thiopurine methyltransferase?
Health Conditions Related to Genetic Changes Changes in the TPMT gene cause TPMT deficiency, which is a reduction in the activity of the TPMT enzyme. Without enough of this enzyme, the body cannot “turn off” thiopurine drugs by metabolizing them into inactive compounds.
What does low TPMT activity mean?
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.
What is a TPMT blood test used for?
Why is TPMT Testing Important? Detection of individuals with low thiopurine methyltransferase (TPMT) activity who are at risk for excessive myelosuppression or severe hematopoietic toxicity when taking thiopurine drugs.
What does TPMT do to azathioprine?
Patients with TPMT deficiency treated with standard doses of azathioprine or 6-mercaptopurine are at significantly increased risk of myelosuppression, bleeding, infection, and death associated with increased levels of cytotoxic 6-thioguanine nucleotide levels in the red blood cells.
What is a normal TPMT level?
Normal TPMT activity: 25-65 U/mL – Individuals are predicted to be at low risk of bone marrow toxicity as a consequence of standard thiopurine therapy; no dose adjustment is recommended.
What drugs are thiopurines?
MN There are 3 types of thiopurines that have been used for inflammatory bowel disease (IBD) therapy: azathioprine, 6-mercaptopurine, and thioguanine. The first 2 are approved for the treatment of IBD, and the third has been tested in clinical trials.
What does TPMT mean in medical terms?
Abbreviations. TPMT, thiopurine methyltransferase. TGN, thioguanine nucleotide. IBD, inflammatory bowel disease.
What do high TPMT levels mean?
High TPMT activity: > 44.0 U/mL – Individuals are not predicted to be at risk for bone marrow toxicity (myelosuppression) as a consequence of standard thiopurine dosing, but may be at risk for therapeutic failure due to excessive inactivation of thiopurine drugs.
How much does TPMT test cost?
Costs: US$7142 for CC, US$5877 for TPMT + MM and US$6441 for MM and US$3861 for TPMT.
What is the importance of measuring TPMT in patients taking azathioprine?
At the start of azathioprine or mercaptopurine therapy, measurement of TPMT activity has a role in identifying the 1 in 300 patients who are at risk of severe myelosuppression when treated with standard thiopurine dosages.
Is azathioprine a thiopurine?
MN There are 3 types of thiopurines that have been used for inflammatory bowel disease (IBD) therapy: azathioprine, 6-mercaptopurine, and thioguanine.
What is the blood test for azathioprine?
Before prescribing azathioprine, your doctor will order a blood test for an enzyme called TPMT, also known as thiopurine methyltransferase (thio-pew-reen meth-ile-trans-fe-raise). Enzymes are proteins in your body that can help to break down certain substances or chemicals.
What are the risk factors for thiopurine toxicity?
Another 11 percent have moderately reduced levels of TPMT activity that increase their risk of hematopoietic toxicity with thiopurine drug treatment. TPMT deficiency results from changes in the TPMT gene. This gene provides instructions for making the TPMT enzyme, which plays a critical role in breaking down (metabolizing) thiopurine drugs.
What causes bruising and bleeding in patients with thiopurine toxicity?
A shortage of platelets (thrombocytopenia) can cause easy bruising and bleeding. Many healthcare providers recommend that patients’ TPMT activity levels be tested before thiopurine drugs are prescribed.
What is low-activity TPMT?
The TPMT gene can be classified as either low-activity or high-activity. When the gene is altered in a way that impairs the activity of the TPMT enzyme, it is described as low-activity.