丙型病毒性肝炎肝损害患者血小板减少机制的探讨

A study on the mechanism of thrombocytopenia in patients with liver damage from hepatitis C virus:analysis of 278 cases of bone marrow image

目的通过对丙型病毒性肝炎(hepatitis C,HCV)肝损害患者骨髓象的分析,探讨骨髓巨核细胞发育成熟对血小板减少的影响。方法将2010年2月至2015年10月解放军第三〇二医院收治的278例无脾功能亢进或已行脾切除、且排除其他肝炎病毒重叠感染、自身免疫性肝炎及脂肪肝的丙型病毒性肝炎患者作为研究对象(其中丙型慢性肝炎患者120例、丙型肝炎肝硬化患者80例、丙型肝衰竭肝炎患者23例、HCV肝炎血小板正常患者55例),采用骨髓图象分析系统对患者异常形态的巨核细胞进行分析,并检测所有患者空腹静脉血的丙型肝炎病毒定量(hepatitis C virus RNA,HCV RNA)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、血小板计数(platelet,PLT)、网织血小板(reticulated platelet,RP)、平均血小板体积(mean platelet volum,MPV)、血小板分布宽度(platelet distribution width,PDW)等指标,采用SPSS 19.0统计软件对各项指标进行统计学分析。结果随着丙型肝炎患者肝损害的加重,HCV RNA含量、APRI评分及PDW、RP均明显高于对照组(HCV肝炎血小板正常组),差异有统计学意义(P<0.05),PLT均明显低于对照组,差异有统计学意义(P<0.05);HCV RNA含量、APRI评分与病程、血小板功能指标呈正相关,与血小板计数指标呈负相关;巨核细胞发生了幼稚巨核细胞增多(>7个)、体积偏小、可见幼稚产板巨核细胞、产板巨核细胞减低或消失(0~2个)、巨核细胞破坏明显、裸核增多(>20个)、空泡变性(细胞质出现大小不一空泡或空泡呈环状排列于浆缘)、产血小板数量少的巨核细胞、巨核细胞周围血小板少于3~5颗、出现多分叶核巨细胞及变性巨核细胞等一系列发育异常及形态学的改变。结论丙型肝炎病毒含量与血小板数、质量及骨髓巨核系统发育成熟具有相关性,可能是引起血小板减少的因素之一。

Objective To study the bone marrow megakaryocyte maturation on platelet count and function in hepatitis C（HCV）patients at different stages of liver damage. Methods Hepatitis C patients were recruited from February 2010 to October 2015 at the 302 Military Hospital in Beijing,China.Of all hepatitis C patients recruited,278 cases suffered either hypersplenism or splenectomy,and excluded superinfection with other hepatitis viruses,autoimmune hepatitis or fatty liver;120cases are chronic hepatitis C,80 hepatitis C cirrhosis,23 patients with liver failure,55 control cases showed normal platelets.Laboratory test include：bone marrow cytology and quantitative hepatitis C virus（HCV RNA）,aspartate aminotransferase（AST）,platelet count（PLT）,reticulated platelets（RP）,mean platelet volume（MPV）,platelet distribution width（PDW）and etc.SPSS 19.0software was used for data analysis. Results With the progression of hepatitis C,HCV RNA,APRI scores,PDW and RP were significantly higher while PLT lower in progressive hepatitis C patients that in control patients with normal platelets（P〈0.05）HCV RNA and ARPI scores showed positive correlation with disease duration and platelet function but negative correlation with platelet counts.Abnormal morphologic changes of megakaryocytes in bone marrow include：increased promegakaryocyte（7）,immature placental megakaryocytes appeared,decreased or disappeared placental megakaryocytes,damaged naked nuclear megakaryocytes increased（20）,vacuolar degeneration,fewer（3-5）platelets around megakaryocyte,multi-leaf and degenerated nuclei. Conclusions Hepatitis C progression with abnormal megakaryocytes is correlated with platelet counts and function.