凝血相关因子与细胞因子在造血干细胞移植早期的临床意义  

Significance of clotting factors and some cytokines in the early development of hematopoietic stem cell transplantation

作　　者：周莉莉[1] 朱倩[1] 韩悦[1] 胡璐萍[1] 赵世香[1] 高海丽[1] 张威[1] 胡晓慧[1] 吴德沛[1] 

机构地区：[1]苏州大学附属第一医院血液科江苏省血液研究所卫生部血栓与止血重点实验室,江苏苏州215006

出　　处：《苏州大学学报（医学版）》2012年第1期107-111,共5页Suzhou University Journal of Medical Science

摘　　要：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�Objective To illustrate the early alteration of clotting factors and specific cytokines in the recipients of hematopoietic stem-cell transplantation （HSCT） and then determine their value in transplantation-associated thrombotic and other complications. Methods Ninty five patients undergoing HSCT are enrolled in this study. Clotting factors and specific cytokines parameters were measured by an enzyme linked immunosorbent assay on platelet poor plasma samples obtained from patients during conditioning therapy and then weekly until four weeks after HSCT. According to the occurrence of transplant-associated complications, four groups were classified as the thrombus group （n = 5 ）, the aGVHD group （n = 29 ）, the infection group （n = 19） and the non-complication group （n =41 ）. Systemic analysis was performed for the role of clotting factors and cytokines in the transplantation-associated thrombotic complications. Results Significant increase in PAI-1 was detected after pre-conditioning treatment, followed by an especial dimition on the week performing transplantation （week 0 ） , then increased that in the prolonged time after transplantation. Significant increase was found in the level of PAI-1 and t-PA in the thrombus group compared with the aGVHD group （P 〈 0.01 ） ;Significant diminution was found in the level of PC in the aGVHD group compared with that in the infection group（P 〈0. 01 ） ; TNF-αlevels in aGVHD patients undergoing Allo-HSCT were already higher than those in the normal control group before conditioning treatment （P 〈 0.01 ） , the TNF-α level in other patients did not significantly change during this course. TNF-αlevel in all patients was even higher 4 days after conditioning treatment and reduced after conditioning treatment （ P 〈 0.05 ）. TNF-αincreased in patients with the onset of aGVHD, thrombosis and infection, which was most significant in the aGVHD group, and less significant in infection group than those in the thrombosis group （P 〈 0.05 �

关 键 词：移植相关性血栓病变 细胞因子 造血干细胞移植 肝静脉闭塞病 血栓性微血管病 

分 类 号：R551.3[医药卫生—血液循环系统疾病]