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目的探讨硫唑嘌呤导致血液系统危象的规律和发生机制。方法8例曾经口服硫唑嘌呤后出现血液系统危象者为病例组,分析其副作用发生的临床特征。选择16例同病种、同期服用过硫唑嘌呤,而没有出现血液系统损害的患者为对照组。盲法检测这两组病人红细胞巯嘌呤甲基转移酶(TPMT)的活性。采用Wilcoxon秩和检验的方法,分析两组间TPMT活性的差异。结果8例均表现为严重的白细胞及血小板减少和严重脱发。时间为使用硫唑嘌呤的第22~31日,中位数26d。血白细胞谷值(0.3~0.6)×109/L,血小板谷值(3.0~9.0)×109/L;有6例检查骨髓象均显示骨髓增生低下。全部病人在停用硫唑嘌呤后11~18d后血象完全恢复正常。病例组的TPMT活性为0.16～2.91U/ml红细胞(RBC),对照组的TPMT活性为3.82～21.68U/mlRBC,Z=3.919,P=0.0001,差异有统计学意义。结论小剂量硫唑嘌呤导致血液系统危象主要与TPMT的活性有关,TPMT活性明显低下者,可以在用药第3～4周时发生严重副作用。
Objective To investigate the regularity and mechanism of azathioprine-induced hematological crisis. Methods Eight cases of blood system crisis after azathioprine was taken as the case group, and the clinical features of the side effects were analyzed. Sixteen patients with the same disease and azathioprine taken over the same period without any blood system damage were selected as the control group. Blind testing of erythrocyte thiopurine methyltransferase (TPMT) activity in these two groups of patients. Wilcoxon rank sum test was used to analyze differences in TPMT activity between the two groups. Results 8 cases showed severe leukopenia and thrombocytopenia and severe hair loss. Time for the use of azathioprine 22 to 31 days, the median 26d. The white blood cell (0.3 ~ 0.6) × 109 / L and the platelet valley (3.0 ~ 9.0) × 109 / L were detected in 6 cases. All patients after the abolition of azathioprine 11 ~ 18d after the blood returned to normal. The TPMT activity in case group was 0.16-2.91U / ml, the TPMT activity in control group was 3.82-21.68U / ml RBC, Z = 3.919, P = 0.0001, the difference was statistically significant. Conclusions The risk of hematological crisis caused by low dose of azathioprine is mainly related to the activity of TPMT. The patients with significantly lower TPMT activity may have serious side effects during the 3rd to 4th weeks of treatment.