Pihusch R, Höhnberg B, Salat C, Pihusch M, Hiller E, Kolb H J
Medizinische Klinik III-Grosshadern, Klinikum der Ludwig-Maximilians-Universität, Marchioninistr. 15, 81377 München, Germany.
Ann Hematol. 2002 Aug;81(8):454-61. doi: 10.1007/s00277-002-0494-z. Epub 2002 Aug 10.
The conditioning regimen preceding hematopoietic stem cell transplantation (HSCT) causes a rapid decrease in the platelet count and signs of disseminated intravascular coagulation, possibly indicating platelet activation. As impacts during the conditioning regimen may predict later transplantation-associated complications, we investigated changes in platelet membrane glycoproteins (GP) and the liberation of microparticles. Platelet receptors and granules of 49 patients undergoing HSCT were evaluated by flow cytometric analysis before and after the different phases of the conditioning regimen [chemotherapy, total body irradiation (TBI), therapy with antithymocyte globulin (ATG)] and final transplantation. Following chemotherapy a high surface expression of CD62P, a low mepacrine staining, and a reduced surface expression of CD42b (part of the GP Ib/V/IX complex) were found, indicating an irreversible activation of platelets. In addition, elevated levels of circulating microparticles were observed, which may reinforce the thrombosis risk in these patients. Treatment with ATG leads to an elevated surface expression of PAC-1 epitopes, which are neoepitopes appearing after activation of GP IIb/IIIa. However, a significant degranulation was not detectable, which may be the consequence of inhibitory influences on platelets during ATG-induced cytokine release syndrome. TBI and transplantation itself had no influence on platelets. This study was able to demonstrate activating effects on platelets by certain phases of the conditioning regimen in patients receiving HSCT. Chemotherapy, in particular, leads to a strong and irreversible platelet activation and a generation of microparticles, which may cause an increased thrombosis risk. Our findings underline the impact of platelets on the pathogenesis of hemostatic complications during HSCT.
造血干细胞移植（HSCT）前的预处理方案会导致血小板计数迅速下降及弥散性血管内凝血迹象，这可能表明血小板被激活。由于预处理方案期间的影响可能预测后期与移植相关的并发症，我们研究了血小板膜糖蛋白（GP）的变化及微粒的释放。通过流式细胞术分析，对49例接受HSCT的患者在预处理方案的不同阶段[化疗、全身照射（TBI）、抗胸腺细胞球蛋白（ATG）治疗]及最终移植前后的血小板受体和颗粒进行了评估。化疗后发现CD62P的高表面表达、低米帕林染色及CD42b（GP Ib/V/IX复合物的一部分）表面表达降低，表明血小板发生了不可逆激活。此外，观察到循环微粒水平升高，这可能会增加这些患者的血栓形成风险。ATG治疗导致PAC-1表位的表面表达升高，PAC-1表位是GP IIb/IIIa激活后出现的新表位。然而，未检测到明显的脱颗粒现象，这可能是ATG诱导的细胞因子释放综合征期间对血小板产生抑制作用的结果。TBI及移植本身对血小板没有影响。本研究能够证明接受HSCT患者的预处理方案某些阶段对血小板有激活作用。特别是化疗会导致强烈且不可逆的血小板激活及微粒生成，这可能会增加血栓形成风险。我们的研究结果强调了血小板在HSCT期间止血并发症发病机制中的作用。
