D-二聚体/纤维蛋白原比值与急性早幼粒细胞白血病患者出血的相关性研究

Correlation between D-Dimer/Fibrinogen Ratio and Bleeding in Patients with Newly Diagnosed Acute Promyelocytic Leukemia

目的:进一步探索预测初发急性早幼粒细胞白血病(APL)相关出血程度的更优指标。方法:根据WHO出血分级标准,对131例APL患者治疗前的出血事件进行分级并分组(0、1、2级为无出血或轻度出血组,3、4级为严重或致命性出血组),并统计各组患者性别、年龄、血红蛋白(Hb)、白细胞(WBC)和血小板(PLT)、外周血淋巴细胞比例(LYMPH%)及单核细胞比例(MONO%)、骨髓及外周血早幼粒细胞百分比、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)水平、D-二聚体(D-D)、D-二聚体/纤维蛋白原比值(DFR)。结果:131例患者中110例为无出血或轻度出血,21例为严重或致命性出血。单因素分析结果显示,与无出血或轻度出血组相比,合并严重或致命性出血的患者外周血早幼粒细胞比率、WBC、D-D、DFR较高,PT延长,LYMPH%降低。多因素分析结果显示,DFR(OR=1.054,95%CI:1.024-1.084,P<0.001)及外周血早幼粒细胞比率(OR=1.026,95%CI:1.002-1.051,P=0.033)为出现严重或致命性出血的独立危险因素。外周血早幼粒细胞比率、D-D和DFR的ROC曲线下面积(AUC)分别为0.748、0.736、0.809。外周血早幼粒细胞比率与D-D诊断效能无统计学差异(P=0.8708);与D-D相比,DFR具有更高的预测价值(P=0.0302)。DFR的最佳cut-off值为16.50,此时的敏感度为90.5%,特异性为70.0%。结论:DFR在预测初发APL相关出血程度中具有明显的优势,DFR值越大提示出血程度越严重,当DFR>16.50时,严重或致命性出血风险增大。

Objective:To further explore the better indicators for predicting the degree of bleeding associated with newly diagnosed acute promyelocytic leukemia(APL).Methods:A total of 131 patients with newly diagnosed APL were classified according to WHO bleeding scales before treatment and divided into two groups:scales 0,1 and 2 were included in no severe bleeding group,scales 3 and 4 were included in severe bleeding group.The information of the patients were collected,including sex,age,hemoglobin(Hb),white blood cell(WBC)count and platelet(PLT)count,peripheral blood lymphocyte percentage(LYMPH%),peripheral blood monocyte percentage(MONO%),percentage of leukemic cells in pripheral blood and bone marrow,prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB)levels,D-dimer(D-D),D-dimer/fibrinogen ratio(DFR).Results:Among 131 patients,110 were classified as no severe bleeding,and 21 were severe bleeding.The results of univariate analysis showed that patients with severe bleeding had significantly higher percentage of leukemic cells in pripheral blood,WBC,D-D,and DFR,as well as longer PT and lower LYMPH%,compared to those with no severe bleeding.Multivariate analysis revealed that DFR(OR=1.054,95%CI:1.024-1.084,P<0.001)and percentage of peripheral blood leukemic cells(OR=1.026,95%CI:1.002-1.051,P=0.033)were independent risk factors for severe bleeding.The area under ROC curve(AUC)of peripheral blood leukemic cells,D-D and DFR were 0.748,0.736 and 0.809,respectively.There was no statistical difference between the peripheral blood leukemic cells and D-D in diagnostic efficacy(P=0.8708).Compared with D-D,DFR had a higher predictive value(P=0.0302).The optimal cut-of f value of DFR was 16.50,with a sensitivity of 90.5%and a specificity of 70.0%.Conclusion:DFR has a significant advantage in predicting the degree of bleeding associated with newly diagnosed APL.The greater the DFR value,the heavier the degree of bleeding.The risk of severe or fatal bleeding increases when DFR is greater than 16.50.