急性白血病并发出血患者的止凝血特点及其与预后的关系

Clinical and prognostic significance of hemostatic molecular markers in acute leukemia with bleeding

目的 :研究急性白血病 (AL)并发不同程度出血患者的止凝血异常特点及其与预后的关系。方法 :采用ELISA方法检测 93例AL患者血浆组织因子 (TF)、组织因子途径抑制物 (TFPI)、凝血酶 抗凝血酶复合物(TAT)、纤溶酶 抗纤溶酶复合物 (PAP)、尿激酶型纤溶酶原激活物 (u PA)、尿激酶型纤溶酶原激活物受体 (u PAR)、D 二聚体 (D D)的含量。结果 :仅有TF、TAT、D D升高者 ,临床上大多表现为轻度出血 ;除TF、TAT、D D显著升高外 ,还伴有u PA、u PAR、PAP高于无出血对照组者 ,临床上以重度出血为主。TAT、PAP、D D对弥散性血管内凝血前期 (pre DIC)诊断的灵敏度分别为 88.5 7%、97.14%和 85 .70 % ,特异性为 69.5 7%、76.0 9%和89.13 % ;联合应用三个指标 ,其灵敏度为 80 .0 0 % ,特异性为 95 .65 %。u PA、u PAR持续增高者预后差 ,2年无复发生存率 (RFS)和 2年总生存率 (OS)显著降低。结论 :轻度出血主要由高凝、继发性纤溶亢进等引起 ,而原发性纤溶亢进则是重度出血最主要的原因 ;TAT、PAP、D D对 pre DIC的诊断有重要意义 ;多项分子标志物的联合应用可提高pre DIC的确诊率。TF对DIC的发展和进程具有预示作用。u PA、u

Objective:To study the characteristic of hemostatic disorders in acute leukemia(AL) and their relationship with bleeding symptom and prognosis.Method:A series of hemostatic molecular markers, including TAT,TF,TFPI,PAP ,u-PA ,u-PAR and D-D were measured in 93 patients with acute leukemia (AL) .Result:Plasma levels of TAT,TF,D-D were higher in patients with mild bleeding while PAP,u-PA,u-PAR level were markedly elevated in patients with severe bleeding. The sensitivity of TAT,PAP and D-D for the diagnosis of pre-DIC were 88.5% , 97.14% and 85.70%, whereas the specificity of those molecular markers for the diagnosis of pre-DIC were 69.57%, 76.09% and 89.13%. By combining the results of TAT,PAP and D-D, diagnostic sensitivity was 80%,diagnostic specificity was 95.56%. Persistent high levels of u-PA,u-PAR were correlated with short duration of relapse-free survival (RFS) and overall survival (OS).Conclusion:Hyperfibrinolysis might be the main reason of bleeding in patients with sever hemorrhage,While hemostatic disorder in patients with mild hemorrhage was hypercoagulability; The hemostatic molecular markers TAT,PAP and D-D were useful for the diagnosis of pre-DIC, while combinations of hemostatic molecular markers increases the specificity of diagnosis. TF was an important marker to predict the development and prognosis of DIC. u-PA, u-PAR may be considered as useful markers for prognosis.