普萘洛尔和5-单硝酸异山梨醇酯改善肝硬化患者血小板减少症的随机对照研究

The randomized controlled trial of isosorbide mononitrate plus propranolol compared with propranolol alone in the treatment of thrombocytopenia in patients with cirrhosis

目的探讨普萘洛尔(PR)和5-单硝酸异山梨醇酯(IM)改善肝硬化患者血小板减少症的有效性。方法前瞻性研究63例肝硬化血小板减少症患者和18例健康体检者。将病例组再随机分为3组,即PR+IM组、PR组、IM组,在治疗前、治疗2、4、8周后时,各组均在清晨空腹由同一医生用彩色多普勒超声仪测量门静脉宽度、脾脏厚度、脾脏指数,同时用全自动血细胞分析仪测定血小板计数。结果63例患者除12例因不能耐受中途退出外,其余51例患者中IM组血小板数、门静脉宽度、脾脏厚度、脾脏指数在各时段差异均无统计学意义(P>0.05)。治疗4、8周后PR+IM组和PR组的血小板数均高于治疗前(P<0.05),门静脉宽度、脾脏厚度均低于治疗前(P<0.05)。但在各时段PR+IM组与PR组比较,血小板数、门静脉宽度、脾脏厚度、脾脏指数差异均无统计学意义(P>0.05),在PR+IM组、PR组及IM组各组间及治疗前后各时段脾脏指数差异均无统计学意义(P>0.05)。PR+IM组和PR组及IM组的血小板数、门静脉宽度、脾脏厚度、脾脏指数与对照组相比,差异均有统计学意义(P<0.01)。结论单用IM不能改善肝硬化患者血小板减少症,PR可以显著改善肝硬化患者血小板减少症。与PR组相比,PR+IM联合组并不能进一步改善肝硬化患者的血小板减少症。与对照组相比,PR改善血小板计数的水平是有限的。

Objective To explore the clinical significance of propranolol（PR） and isosorbide mononitrate（IM） in the treatment for thrombocytopenia in patients with cirrhosis. Methods Sixty-three patients with cirrhosis and thrombocytopenia（ fewer than 7 × 10^10/L） as observation group were randomly divided into PR group, IM group and PR ＋ IM group, and 18 normal volunteers as healthy group were enrolled in this prospective study. All the studies were performed in the morning after an overnight fast. Platelet counts were determined by auto blood cell analyzer. Spleen index, the inner diameters of portal veins and the thickness of spleen were measured on ultrasonography by the same doctor before treatment, at 2 weeks, 4 weeks and 8 weeks after treatment. Results Twelve patients with cirrhosis were dismissed due to being intolerant of the drug＇ s side effect. In any time point, platelet counts, spleen index, the inner diameters of portal veins and the thickness of spleen had no significant difference in IM group （ P 〉 0.05）. Platelet counts at 4 weeks and 8 weeks after treatment were significantly higher than those before treatment ifi PR group and PR ＋ IM group （P 〈 0.05 ）. The inner diameters of portal veins and the thickness of spleen at 4 weeks and 8 weeks after treatment were significantly reduced compared with those before treatment in PR group and PR ＋ IM group （P 〈 0.05）. Platelct counts, spleen index, the inner diameters of portal veins and the thickness of spleen had no significant difference between PR group and PR ＋ IM group in any time （P 〉 0.05）. Spleen index had no significant difference among in IM group, PR group and PR ＋ IM group in any time （P 〉 0.05 ）. Compared with the healthy group, platelet counts, spleen index, the inner diameters of portal veins and the thickness of spleen had significant difference in IM group, PR group and PR ＋ IM group in all time point （P 〈 0.01 ）. Conclusion IM alone can not ameliorate thrombocytopenia, but PR alone can ameliorate significantly thrombocytopenia in patients with cirrhosis. IM plus PR could not increase the effect of ameliorating thrombocytopenia in patients with cirrhosis compared with PR alone.