RBC 6-TGN and hematological parameters in patients with Crohn's disease treated by azathioprine

Objective: The immunosuppressive properties of azathioprine (AZA) are mediated by intracellular metabolism of 6-MP into its active metabolites 6-thiguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP). The aims of this study were to correlate red blood cell (RBC) 6-TGN and hematological parameters and their change in adult patients with Crohn's disease (CD) treated by AZA and to determine independent factors enabling determination of RBC 6-TGN. Methods: RBC 6-TGN concentration was determined with high performance liquid chromography (HLPC) performed on 74 heparinized blood samples from 32 patients. Changes of hematological parameters were measured for each RBC 6-TGN concentration. RBC 6-TGN concentration above 235 pmol/8x10(8) RBC was proposed as the therapeutic level in patients treated by AZA. Correlations between the various parameters were assessed as appropriate. Logistic regression analysis was used to determinate independent variables. P < 0.05 was considered significant. Results: There was a positive correlation between RBC 6-TGN and decreased red cell count (Delta RBC) (r = 0.314; P = 0.006), platelet count (Delta Platelets) (r = 0.314; P = 0.007), White cell count (Delta WC) (r=0.241; P = 0.04) and neutrophil count (Delta PMN) (r = 0.292; P = 0.02). RBC 6-TGN in the therapeutic zone was positively correlated with mean corpuscular volume (MCV) (r = 0.527; P = 0.01), mean corpuscular hemoglobin concentration (MCHC) (r = 0.437; P = 0.04), increase in MCV (Delta MCV) (r = 0.512; P = 0.012), decrease in White cell count (Delta WC) (r = 0451; P = 003) and in neutrophil count (Delta PMN) (r = 0.463; P = 0.03). Multivariate analysis showed that low activity of CD (P < 0.02), young age at onset of treatment by AZA (P < 0.03) and a low red cell distribution width (RDW) (P = 0.003) were independent factors for RBC 6-TGN situated in therapeutic zone. RBC 6-TGN could be determined by logistic regression from AZA dose (mg/kg/d) and MCV increase. Conclusion: This study confirms that hematological parameters or their change can be used to determine whether RBC 6-TGN concentration has reached the therapeutic level. Logistic regression analysis showed that decreased RDW and increased MCV were independent factors for RBC 6-TGN level.