恶性血液肿瘤中ADAMTS13活性与TSP1水平改变

Changes of ADAMTS13 Activity and TSP1 Level in Patients with Hematologic Malignancies

目的:观察血管性血友病因子裂解蛋白酶(von Willebrand factor cleaving protease,ADAMTS13)活性、血管性血友病因子(von Willebrand factor,v WF)及凝血酶敏感蛋白1(thrombospondin 1,TSP1)水平在恶性血液肿瘤患者治疗前后的变化,并探讨其相关的临床意义。方法:收集82例恶性血液肿瘤(包括20例急性白血病,48例恶性淋巴瘤,14例多发性骨髓瘤)患者和45例与之匹配的健康对照者的血浆标本,用酶联免疫吸附试验(ELISA)检测2组血浆中的v WF抗原和TSP1水平,用残余胶原结合试验(R-CBA)检测2组血浆中的ADAMTS13活性水平。结果:初发恶性血液肿瘤患者血浆中ADAMTS13活性(71.48±19.62)%明显低于正常对照组(92.31±21.82)%(P<0.05);v WF抗原水平和TSP1水平高于正常对照组(P<0.05)。初发组血浆中ADAMTS13活性(71.48±19.62)%低于治疗后缓解组(89.84±20.70)%(P<0.05);初发组v WF抗原水平高于治疗后缓解组(P<0.05)。在82例初发恶性血液肿瘤中有25例合并感染,治疗前合并感染者的ADAMTS13活性(49.80±18.44)%明显低于无感染组(73.82±21.41)%(P<0.05);感染组v WF抗原水平与TSP1水平明显高于无感染组(P<0.05)。治疗过程中有8例发生了血栓事件,发生血栓事件的患者血浆中ADAMTS13活性较无血栓组明显降低(P<0.05);8例急性早幼粒细胞白血病中有1例合并弥散性血管内凝血。结论:恶性血液肿瘤患者中ADAMTS13活性降低和TSP1水平升高,而发生感染及血栓事件的恶性血液肿瘤患者中ADAMTS13活性进一步降低。检测恶性血液肿瘤患者血浆中的ADAMTS13活性和TSP1水平有可能更好地预防感染及血栓事件的发生。

Objective：To investigate the changes of thrombospondin 1（TSP1） level and von Willebrand factor cleaving protease（ADAMTS13） activity in the patients with hematologic malignancies before and after treatment and to evaluate their clinical significance.Methods：Eighty-two patients with hematologic malignancies were enrolled in this study,among them 20 patients were with acute leukemia,48 patients were with lymphoma and 14 patients were with multiple myeloma.The plasma samples of 82 patients with hematologic malignancies and 45 healthy controls were collected.The activities of ADAMTS13 were evaluated by residue collagen binding assay（R-CBA）,the levels of TSP1 and vWF antigen were measured by enzyme-linked immunosorbent assay（ELISA）.Results：The activity of plasma ADAMTS13 in patients with hematologic malignancies was lower than that of normal controls（P〈0.05）.The levels of vWF antigen and TSP1 in the patients with hematologic malignancies were higher than those in normal controls（P〈0.05）.After standard induction chemotherapy,the ADAMTS13 activity of the patients with hematologic malignancies at the complete remission was higher than that before therapy（P〈0.05）;the vWF antigen level was significantly lower than that in the patients with hematologic malignancies before therapy（P〈0.05）,but still higher than that in controls（P〈0.05）.There were 25 infection patients in 82 cases of hematologic malignancies,and the ADAMTS13 activity in the patients with newly diagnosed hematologic malignancies complicated with infection before therapy was obviously lower than that in the patients with hematologic malignancies without infection（P〈0.05）,the levels of vWF antigen and TSP1 were significantly lower than that in patients without infection（P〈0.05）.In the process of treatment,8 patients have been speculated to suffer from thrombus,and the ADAMTS13 activity in the patients with thrombus was obviously lower than that in the patients without thrombus（P〈0.05）.Conclusion：Low ADAMTS13 activity and high TSP1 level may participate in the progress of hematologic malignancies,the infection and thrombotic events may lead to further reduction of the ADAMTS13 activity.Assaying the level of ADAMTS13 activity in the patients with malignant tumor may be helpful to prevent the infection and thrombosis in the patients with hematologic malignancies.