| Objective:Patients with liver diseases often have multi-system dysfunction,including changes in the blood system.Similarly,blood system diseases can also involve the liver and produce corresponding clinical manifestations.Cytopenia is the most common abnormal hematological index in patients with liver diseases,which is closely related to clinical prognosis.Only a small number of patients have primary hematological diseases involving the liver.In the past,hypersplenism was considered to be the main factor for liver diseases complicated by cytopenia.Recent studies have revealed that there are obvious abnormal bone marrow hematopoietic system functions in patients with liver cirrhosis[1],which may be the main reason why conventional drugs are not effective in liver diseases complicated by cytopenia.The occurrence of cytopenias is closely related to the clinical stage of liver diseases.The analysis of bone marrow-related examination indicators in patients with liver diseases complicated by cytopenia is of great significance to clarify the basic situation of the bone marrow hematopoietic system in patients at various stages.The purpose of this study was to explore the distribution characteristics of peripheral blood routine,blood smears,and bone marrow cell-related indicators in patients with different cytopenias,as well as the correlation between the indicators,so as to provide a reference for the subsequent development of hematopoietic cell therapy based on the bone marrow hematopoietic system.Method:This study was a retrospective study,including 371 patients with liver diseases complicated by cytopenia who were hospitalized in the Department of Hepatobiliary and Pancreatic Medicine,First Hospital of Jilin University from January 2016 to January 2022 and underwent bone marrow cytology examination.The general clinical data（age,gender）,peripheral blood smears,bone marrow cytology,bone marrow biopsy results and laboratory test results（blood routine,coagulation routine,liver function,blood biochemistry,blood lipids,CRP,PCT）,imaging examination results and complications（ascites,pleural effusion,gastrointestinal hemorrhage,hepatic encephalopathy）of the patients were collected,calculating the neutrophil-lymphocyte ratio（NLR）,end-stage liver disease model（Model for End-stage Liver Disease,MELD）score to record whether patients have liver cirrhosis.The patients were divided into groups according to cytopenia:one-line reduction group（including thrombocytopenia,leukopenia,anemia）,two-line reduction group（including thrombocytopenia with anemia,thrombocytopenia with leukopenia,anemia with leukopenia）and three-line reduction group,using SPSS 26.0 software,R 4.1.3 to analyze the data,using Graphpad Prism9 software to draw.Result:1.Baseline distribution of peripheral blood and bone marrow-related indicators（1）Baseline blood film characteristicsAmong the 371 patients,the proportion of eosinophils was increased in 7 patients,accounting for 1.9%;the proportion of basophils was increased in 23 patients,accounting for 6.2%;the proportion of monocytes was increased in 99 patients,accounting for 1.9%.The proportion of lymphocytes was increased in 70 patients,accounting for 18.9%;atypical lymphocytes were seen in 84 patients,accounting for22.6%;only 1 patient had plasma cells,accounting for 0.4%;22 patients had pathological hematopoiesis,accounting for 5.9%,of which 11 patients showed myeloid pathological hematopoiesis,9 patients showed myeloid and erythroid pathological hematopoiesis,1 patient showed myeloid and megakaryoid pathological hematopoiesis,and 1 patient showed erythroid pathological hematopoiesis.Among the 371 patients,68 blood smears showed that the morphology and proportion of each cell were generally normal,accounting for 18.3%,and the rest had abnormal cell proportions or abnormal morphology.Among them,191 patients showed mature red blood cells of different sizes,accounting for 51.5%;78 patients showed the enlarged central light-stained area of mature red blood cells,accounting for 21.0%;45 patients showed mature red blood cells arranged in a coin-like arrangement,accounting for 12.1%;Oval red blood cells were found in 34 patients,accounting for 9.2%;teardrop red blood cells were found in 37 patients,accounting for 10.0%;target red blood cells were found in 30 patients,accounting for 8.1%;spherocytes were found in 18 patients,accounting for 4.9%.Vacuole degeneration was seen in granulocytes in 14 patients,accounting for 3.8%;toxic granules were seen in 71 patients,accounting for 19.1%.（2）The grading of the cytological proliferation degree of the bone marrow at baseline and the proportion distribution of each lineage of the bone marrowBone marrow hyperplasia grade of 371 patients:0 patient with extremely active hyperplasia,29 patients（7.8%）with markedly active hyperplasia,315 patients（84.9%）with active hyperplasia,26 patients（7.0%）with reduced hyperplasia,1 patient（0.3%）with extremely decreased hyperplasia.The distribution ratio of each lineage in the bone marrow:the granulocyte to erythrocyte ratio was lower than the lower limit of the reference range in 242 patients（65.2%）,within the reference range in 89 patients（24.0%）,and higher than the upper limit of the reference range in 40 patients（10.8%）;the proportion of granulocyte lineage was lower than the lower limit of the reference range in 53 patients（14.3%）,within the reference range in 235 patients（63.3%）,and higher than the upper limit of the reference range in 83 patients（22.4%）;the proportion of erythrocyte lineage was lower than the lower limit of the reference range in 35 patients（9.4%）,within the reference range in 265 patients（71.4%）,and higher than the upper limit of the reference range in 71 patients（19.1%）;the proportion of megakaryocytes lineage was lower than the lower limit of the reference range in 23 patients（6.2%）,within the reference range in 104 patients（28%）,and higher than the upper limit of the reference range in was 244 patients（65.8%）.2.Comparison of indexes between different groups of liver disease complicated with cytopenia（1）Comparison of blood smear indexes among the three groupsThe blood smear indexes of the first-line reduction group,the two-line reduction group,and the three-line reduction group were compared,and the results showed that the differences in the proportion of neutrophils and lymphatic system in the ear blood smears among the three groups were statistically significant（P<0.05）.There was no significant difference in the proportion of mononuclear lines（P>0.05）.The proportion of neutrophils in the two-lineage and three-lineage groups was significantly lower than that in the one-lineage group,and the proportion of lymphoid cells was significantly higher than that in the first-lineage group.（2）Comparison of bone marrow cytology results among the three groupsThe bone marrow cytology results of the first-line reduction group,the two-line reduction group,and the three-line reduction group were compared,there were statistically significant differences in granulocyte-to-erythrocyte ratio,granulocyte-to-lymphocyte ratio,granulocyte-lineage ratio,erythrocyte-lineage ratio,and number of megakaryocytes among the three groups（P<0.05）.There was no statistically significant difference in the proportion of Lymphocytes,monocyte and plasma cells（P>0.05）.The ratio of granulocyte to erythrocyte in the first-line reduction group was significantly higher than that in the third-line reduction group,the proportion of granulocytes and the number of megakaryocytes were significantly higher than those in the two-line reduction group and the three-line reduction group,and the ratio of erythrocytes was significantly lower than that in the three-line reduction group.（3）Comparison of bone marrow biopsy results among the three groupsThe bone marrow biopsy indexes of the first-line reduction group,the two-line reduction group,and the three-line reduction group were compared,and the results showed that the difference in the number of megakaryocytes among the three groups was statistically significant,and the number of megakaryocytes in the first-line reduction group was higher than that in the three-line reduction group.There were no significant differences in hematopoietic area,fat area,trabecular bone,number of megakaryocytes,reticular fiber staining and bone marrow hyperplasia among the three groups（P>0.05）.3.Correlation analysis of bone marrow cytology indexes with laboratory indexes and blood smear indexes（1）Correlation analysis of granulocyte-to-erythrocyte ratio in bone marrow cytology with blood routine and blood smear indexesGranulocyte-to-erythrocyte ratio were positively correlated with WBC（r=0.145,P=0.005）,NE（r=0.126,P=0.015）,NLR（r=0.128,P=0.014）,HBG（r=0.284,P<0.001）,PLT（r=0.147,P<0.004）RBC（r=0.272,P<0.001）,TT（r=0.105,P=0.044）,MELD score（r=0.111,P=0.032）,and was negatively correlated with ALB（r=-0.232,P<0.001）,and the overall correlation was weak.（2）Correlation analysis of bone marrow cytology granulocyte ratio with blood routine and blood smear indexesThe proportion of granulocyte lineage in bone marrow cytology were positively correlated with WBC（r=0.193,P<0.001）,NE（r=0.211,P<0.001）,NLR（r=0.234,P<0.001）,HBG（r=0.202,P<0.001）0.001),PLT（r=0.192,P<0.001）,RBC（r=0.220,P<0.001）,MELD score（r=0.121,P=0.002）,and was negatively correlated with ALB（r=-0.143,P=0.006）,and the overall correlation was weak.Conclusion:1.In patients with liver diseases complicated by cytopenia,the cytological proliferation degree of bone marrow is mainly classified as active proliferation,and the granulocyte-to-erythrocyte ratio is lower than the normal range.Some patients have pathological hematopoiesis,mainly granulocyte pathological hematopoiesis.2.Compared with the first-line and two-line reduction groups,the bone marrow cytology erythrocyte ratio of the third-line increased,the granulocyte ratio decreased,and the number of megakaryocytes decreased.3.The correlation between bone marrow cytology indexes and clinical indexes is weak,and bone marrow cytology can more directly reflect the hematopoiesis of bone marrow in patients with liver diseases. |
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