Laboratory: Clinical Biochemistry  (SPECIAL CHEMISTRY)
Test Name:
THIOPURINE METHYLTRANSFERASE (TPMT) ENZYME ACTIVITY (PHENOTYPE), ERYTHROCYTES - (B)
Test Code: TPMP
Clinical Information:
Alternate Name(s): TPMT ACTIVITY (RBC)
Description: Determining a patient's TPMT status prior to starting therapy with a Thiopurine drug is important for purposes of calculating the optimal drug dosage.
Individuals with low TPMT activity are at risk for life-threatening severe hematopoietic toxicity, while individuals with high TPMT activity present therapeutic resistance to the thiopurine drugs and may develop hepatotoxicity when taking thiopurine drugs (Azathioprine, 6-Mercaptopurine, or 6-Thioguanine).

Recommendations: The TPMP test should only be done once on each patient – TPMT activity does not change. Repeat testing is not done for in province patients.
Patient preparation instructions: 
1) TPMT phenotyping should not be done once a patient is taking Azathiopurine, Thioguanine or 6-Mercaptopurine. The assay for TPMT phenotyping measures the enzyme activity by producing drug metabolite in the assay, so once a patient is taking thiopurine drugs, they are producing the metabolite in vivo and the result of the assay would be falsely elevated. 

2) TPMT activity must be measured prior to RBC transfusion to avoid false indication. If not possible, TPMT genotyping for only the common variants may be used to screen for patients at high risk of thiopurine drug induced toxicity.

3) TPMT enzyme activity can be inhibited by several drugs and may contribute to falsely low results. Patients should discontinue drugs for at least 48 hours prior to TPMT testing: Naproxen, Ibuprofen, Ketoprofen, Furosemide (Lasix), Sulfasalazine (Azulfidine), Mesalamine (Asacol), Olsalazine (Dipentum), Mefenamic acid (Ponstel), Trimethoprim (Proloprim), Methotrexate, Thiazide diuretics, and Benzoic acid inhibitors.

Collection Devices:
EDTA tubes (whole blood) smaller or larger than 4 mL is acceptable as long as the hemoglobin level is provided.
 

Patients should be tested prior to azathioprine or 6-MP administration.

Specimen Required:
Whole Blood: 2.0 mL
Pediatric Whole Blood: 0.5 mL

Collection Information: 
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube.
Special Processing: Do not centrifuge. Do not freeze.
Specimen Stability: 
Ambient: 5 days
Refrigerated: 8 days
Frozen: Unacceptable 


Out of the province (Dynacare) samples MUST be accompanied by hemoglobin result (report) from the same day collection and sent along with the specimen. Hemoglobin report MUST be attached to the requisition and sent along with the specimen

Referral:
Whole Blood: 2.0 mL
Pediatric Whole Blood: 1.0 mL

EDTA tubes (whole blood) smaller or larger than 4 mL is acceptable as long as the hemoglobin level is provided
Pediatric Volume: 1.0 mL (0.4 mL is required for testing)
Shipping & Storage: Send in original collection tube. Prevent blood from freezing.
Testing Laboratory (MB): HSC
 
Requisition:
Reference Values:
ActivityValue (nmol/g Hb/h)
Low<10
Intermediate10-40
Normal>40

Individuals with low TPMT activity are at high risk of bone marrow toxicity with standard thiopurine dosing.
Method of Analysis: Enzymatic / UPLC-Fluorescence

Availability:
Within 1 Week
See Also:
More Information: