Relationship between red cell mean corpuscular volume and 6-thioguanine nucleotides in patients treated with azathioprine

Azathioprine (AZA) is characterized by high interindividual differences in bioavailability and metabolization. The aim of the present study was to analyze, in patients treated with AZA for various immune system disorders, whether the variation in red blood cell mean corpuscular volume (Delta MCV) could be used as an indirect estimation of the level of the active immune modifier metabolite 6-thioguanine nucleotides (6-TGN), In 43 consecutive patients treated with a stable dose of AZA for at least 6 months who were not initially anemic, the erythrocyte 6-TGN levels with routine hematologic parameters were determined two to four times at 1-month intervals. In most patients MCV significantly increased after 3 months of therapy and stabilized after 6 months. The correlation between the daily dose of AZA and the 6-TGN level was mild (r = 0.51; P < .001). A weak correlation was also found between the dose of AZA and the Delta MCV after at least 6 months of therapy (r = 0.36; P < .05), The correlation between Delta MCV and 6-TGN level, however, was much better (r = 0.74; P < .001), The lack of a significant increase in MCV after 3 to 4 months of AZA therapy reflects low 6-TGN levels, sometimes a result of undertreatment. A determination of the 6-TGN level during the first months after AZA therapy is begun will allow more accurate adaptation of the effective dose. We observed that Delta MCV could be used as an indicator of 6-TGN levels after 6 months of AZA treatment. An increase in MCV of at least 6 fL is expected to reflect a 6-TGN level of about 175 pmol/8 x 10(8) red blood cells (probably being within a therapeutic value).