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目的揭示造血干细胞移植(HSCT)早期凝血相关因子及特异性细胞因子的动态改变,探讨其在移植相关性血栓病变及其他并发症中的临床意义。方法采用ELISA法对95例接受HSCT的患者标本进行监测,观察预处理过程以及造血干细胞移植后4周内患者血浆中各种指标的动态改变。根据移植后首先出现的并发症分为4组:平稳组41例、急性移植物抗宿主病(aGVHD)组29例、血栓组6例和感染组19例进行统计分析。结果 HSCT在预处理过程中,纤溶酶原激活剂移植物(PAI-1)水平先升高,移植当周下降,随后又逐步上升;PAI-1和组织型纤溶酶原激活剂(t-PA)在血栓组有明显的升高(均P<0.001),且两者在血栓组和aGVHD组间差异亦有高度统计学意义(均P<0.01)。蛋白C(PC)水平的降低在aGVHD组有高度统计学意义(P<0.001),且在aGVHD与感染组间差异有高度统计学意义(均P<0.01)。预处理前肿瘤坏死因子(TNF-α)水平在aGVHD组已经较正常升高(P﹤0.01),其他患者中未见明显改变。在预处理第4天后所有患者都较前明显升高(P﹤0.05),预处理结束TNF-α较前降低。发生aGVHD、血栓或感染时,TNF-α均明显升高,以aGVHD组升高更为明显,血栓组TNF-α升高水平大于感染组(P﹤0.05)。血栓和aGVHD组的TNF-α在发病前2周即有升高,感染组患者在发病前未见改变。白介素(IL)1-β在移植患者预处理各阶段未见明显变化,发生aGVHD、血栓、感染时IL1-β均有升高,以血栓组升高更明显,aGVHD组较感染组也明显升高(P﹤0.01)。在血栓患者发病前2周明显升高,而aGVHD组于发病前1周升高。结论 (1)血浆PAI-1水平的增高可能是移植相关性血栓病变的特异性指标,提示肝静脉闭塞病(HVDD)、血栓性微血管病(TMA)等血栓并发症的发生。(2)t-PA抗原对aGVHD和血栓有鉴别诊断的意义,PC在aGVHD的早期预测方面有一定的作用。(3)预处理可造成细胞因子TNF-α释放增加。在aGVHD发生时,血清TNF-α水平明显升高且较血栓患者升高更突出;在血栓发生时,血清IL1-β含量明显升高,并高于aGVHD患者。
Objective To reveal the dynamic changes of coagulation-related factors and specific cytokines in early stage of hematopoietic stem cell transplantation (HSCT), and to explore its clinical significance in transplantation-related thrombotic diseases and other complications. Methods Ninety-five patients with HSCT were enrolled in this study. Pretreatment and dynamic changes of various indexes of plasma in patients within 4 weeks after hematopoietic stem cell transplantation were observed. According to the first complications after transplantation, the patients were divided into 4 groups: 41 patients in stable group, 29 patients in acute graft-versus-host disease (aGVHD) group, 6 patients in thrombosis group and 19 patients in infection group. Results In the pretreatment of HSCT, plasminogen activator grafts (PAI-1) levels first increased and then decreased week by week, then gradually increased. PAI-1 and tissue plasminogen activator (t (P <0.001). There was also a significant difference between the two groups in thrombosis group and aGVHD group (all P <0.01). The reduction of protein C (PC) level was highly significant in aGVHD group (P <0.001), and the difference between aGVHD and infection group was highly statistically significant (both P <0.01). Pretreatment tumor necrosis factor (TNF-α) levels in aGVHD group has been higher than normal (P <0.01), no significant change in other patients. All patients were significantly increased on the 4th day after pretreatment (P <0.05), and TNF-α at the end of pretreatment was lower than before. When aGVHD, thrombus or infection occurred, TNF-αincreased obviously, especially in aGVHD group. The level of TNF-α in thrombosis group was higher than that in infection group (P <0.05). Thrombosis and aGVHD group of TNF-α increased in the two weeks before the onset of infection in patients with no change before the onset. Interleukin (IL) 1-β showed no significant changes in all stages of pretreatment of patients with aGVHD, thrombosis, IL1-β were increased during infection, thrombosis increased more significantly, aGVHD group was significantly higher than the infected group High (P <0.01). In patients with thrombosis 2 weeks before onset significantly increased, while aGVHD group increased 1 week before onset. Conclusions (1) The increase of plasma PAI-1 may be the specific index of thrombosis related transplantation, suggesting the occurrence of thrombotic complications such as hepatic veno-occlusive disease (HVDD) and thrombotic microangiopathy (TMA). (2) The significance of t-PA antigen in the differential diagnosis of aGVHD and thrombosis, PC in aGVHD early prediction of a certain role. (3) pretreatment can cause cytokine TNF-α release increased. Serum levels of TNF-α were significantly elevated in patients with aGVHD and were more prominent than those in patients with thrombosis. Serum levels of IL1-β were significantly higher in patients with aGVHD than in patients with aGVHD.