Erythrocyte Mean Corpuscular Volume (MCV) Correlation with Thiopurine Methyl Transferase (TPMT) Activity in Inflammatory Bowel Disease (IBD) Patients Receiving Azathioprine (AZA)/6-Mercaptopurine (6MP)

Background: Azathioprine/6-mercaptopurine therapy leads to variable degree of change in the mean red cell corpuscular volume (MCV). This variability may be related to thiopurine methyl transferase (TPMT) activity of individual patients.

Aim: To study the correlation between TPMT activity and MCV, and the possible use of MCV as surrogate marker for TPMT activity.

Methods: Patients stable on AZA/6-MP for at least 3-months were selected. The MCV pre and post a stable dose period (at least 3-months) was compared. TPMT activity was determined using both radio-assay and mass spectrometer techniques. Comparisons were made in patient groups with normal, deficient, carrier, and high TPMT enzyme activity states. Patients with vitamin and iron deficiency were excluded.

Results: 117-patients were included in the study (Crohn's disease, n=84, ulcerative colitis, n=26, and indeterminate colitis n=7). Overall pre-treatment mean MCV was 88.3 (74–100) and after a stable dose period reached to 91.8 (81–107). 76%-patients had TPMT activity in normal range, 8% in carrier range and 16% had higher than normal activity ranges. The mean pre-treatment MCV in normal, carriers, and high activity groups was 81.6 (74–89), 89 (83–95), 88.3 (74–100), respectively. The MCV after a stable dose period increased significantly in normal, carrier and high activity groups to 86.8 (81–101), 95 (82.7–107), and 87.2 (83–92) respectively. This increase in MCV however, did not differ significantly between the groups

Conclusions: Therapy with azathioprine/6-MP leads to higher MCV. However, in IBD patients, this change does not seem to be directly related with TPMT enzyme activity.