PAI-1在造血干细胞移植早期血栓病变中的临床意义

Clinical significance of plasminogen activator inhibitor-1 （ PAI-1 ） in the early development of HSCT- associated thrombotic complications

目的观察造血干细胞移植早期患者纤溶酶原激活剂抑制物-1（PAI-1）指标的动态改变，探讨其在移植相关性血栓病变中的临床意义。方法采用ELISA法监测95例接受造血干细胞移植的患者在预处理过程中以及干细胞移植后4周内血浆中PAI-1等凝血指标的动态改变。根据移植后并发症的发生情况将患者分为平稳组、急性移植物抗宿主病（aGVHD）组、血栓组以及感染组进行统计学分析。结果造血干细胞移植过程中患者的各项凝血相关指标呈现动态改变。其中PAI-1水平在预处理后升高，移植当周下降，随后又逐步上升。根据移植后首先出现的并发症情况将患者分为四组：平稳组41例、aGVHD组29例、血栓组6例[肝静脉闭塞病（VOD）5例，血栓性微血管病（TMA）1例]和感染组19例。自体移植中发生血栓1例（3．3％），异基因移植组发生血栓5例（7．7％）。移植后发生血栓患者PAI-1水平较发生血栓者无增高，后者又高于自体移植无血栓患者。有并发症的移植患者PAI-1水平明显高于无并发症患者。出现血栓病变的6例患者PAI-1极度升高，为（62．8±7．5）μg/L，明显高于GVHD组[（45．1±9．1）μg/L]和感染组[（50．0±11．2）μg/L]患者的移植后平均水平。结论血浆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VOD、TMA等血栓并发症的发生。PAI-1水平的明显升高有益于移植相关性血栓并发症的早期诊断。

Objective To illustrate the early alteration of plasminogen activator inhibitor-1 （ PAI-1 ） in the recipients of hematopoietic stem cell transplantation （HSCT） and explore its clinical significance in transplantation-associated thrombotic complications. Methods Ninety-five patients undergoing HSCT were enrolled in this study. PAI-1 level and other hemostatic parameters were measured by enzyme linked immu- nosorbent assay（ELISA） in platelet poor plasma samples from patients on conditioning therapy and then week- ly until four weeks after HSCT. Results Significant increase in PAI-1 was detected after conditioning treat- ment, followed by a diminution in the very week on transplantation （week 0） , then increased with in time af- ter transplantation. According to the occurrence of transplant-associated complications, patients were classified into four groups ： thrombus group [ veno-occlusive disease （ VOD ） （ n = 5 ） , thrombotic microangiopathy （TMA） n=1], aGVHD group （n=29）, infection group （n = 19） and non-complication group （n =41）. One of 30 patients （3.3%） was diagnosed as thrombus in the auto-HSCT group, while five of 65 patients （7.7%） did in the allo-HSCT group. PAI-I level of thrombotic patients was significantly increased compared with non-thrombotic subjects, and the patients without thrombotic complications have higher PAI-1 level in the allo-HSCT group than in auto-HSCT group. All the patients with complications presented with significantly in- creased PAI-1 compared with those with no complications （ P 〈 0.05 ）. The six patients with thrombotic complications showed extremely elevated PAI-1 [ （ 62.8± 7.5 ） μg/L ] compared with that of aGVHD patients [ （ 45.1 ± 9.1 ） μg/L ] or infection patients [ （50.0± 11.2） μg/L ] post-HSCT （ P 〈 0.05 ）. ConclusionThe increase in plasma PAl-1 may be a specific mark for transplantation-associated thrombotic complications. Increased PAI-1 reflects the development of thrombotic complications. Extreme elevation of PAI-1 contributes to the early diagonsis of VOD and TMA after HSCT.