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 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 ）. TNF-α began to increase two weeks before complication developed in the aGVHD and thrombosis group, while TNF-α level did not change in the infection group at the same time. IL1-β levels did not change during conditioning treatment but increased in patients with the development of the aGVHD, thrombosis and infections group, levels of IL1-β in thrombtic group increased most significantly, and IL1-β increased more significantly in aGVHD group than that in the infected group （P 〈 0.01 ）. IL1-β in the aGVHD group began to increase one week before complication developed and it in the thrombotic group began to increase two weeks before complication developed. Conclusion （1） Increase in the plasma PAI-1 may be one specific mark for transplantation-associated thrombotic complications. Raised PAI-1 reflects the development of thrombotic complications, The extreme elevation of PAI-1 facilitates the early diagnosis of HVOD and TMA from other transplantation-associated complications. （2） The increased level of t-PA was considered as discriminated value between HVOD and aGVHD. The decreased level of PC was considered as a index marker in the diagnosis of aGVHD. （3） Levels of TNF-α and ILl-13 are closely related to aGVHD or thrombotic complications. Monitoring changes of TNF-α and IL1-β levels contribute to early discovery of aGVHD and thrombotic complications. So the changes of clotting factors and specific cytokines facilitate the early discovery of aGVHD and thrombotic complications.
出处
《苏州大学学报（医学版）》
CAS
2012年第1期107-111,共5页
Suzhou University Journal of Medical Science
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
transplantation-associated thrombotic complications
cytokines
hematopoietic stem celltransplantation
hepatic veno-occlusive disease
thrombotic microangiopathy
