Leinoe E B, Hoffmann M H, Kjaersgaard E, Johnsen H E
The Research Laboratory, Department of Haematology, Herlev University Hospital, Copenhagen, Denmark.
Br J Haematol. 2004 Oct;127(1):76-84. doi: 10.1111/j.1365-2141.2004.05156.x.
Summary Previous findings of megakaryocytic hypogranulation and dysmegakaryocytopoietic features in acute myeloid leukaemia (AML) strongly indicate defects in platelet production. The bleeding tendency of these patients may result from dysregulated platelet production, resulting in thrombocytopenia as well as qualitative platelet defects. The present study examined platelet function at diagnosis in 50 AML patients by whole blood flow cytometry. Following in vitro platelet agonist stimulation, platelet activation markers were analysed and compared with 20 healthy individuals. To detect recent in vivo platelet activation, plasma soluble P-selectin (sP-selectin) was measured. Flow cytometric analysis of platelet activation markers demonstrated reduced CD62P [35.6 vs. 118.5 x 10(3) molecules of equivalent soluble fluorochrome (MESF); P < 0.0001], CD63 (11.3 vs. 50.7 x 10(3) MESF; P < 0.0001), and PAC-1 (41.5 vs. 90.5%; P = 0.0001) while reductions in CD42b were abnormal (45.6 vs. 70%; P < 0.0001). sP-selectin levels were similar in patients and healthy controls (0.04 vs. 0.27 fg/platelet; P = 0.84). The presented data indicate that AML pathogenesis may result in multiple platelet defects, involving adhesion, aggregation, and secretion and demonstrate that flow cytometry is a feasible method for platelet function analysis in patients with thrombocytopenia.
摘要 先前在急性髓系白血病(AML)中发现的巨核细胞颗粒减少和巨核细胞生成异常特征强烈提示血小板生成存在缺陷。这些患者的出血倾向可能源于血小板生成失调,导致血小板减少以及血小板质量缺陷。本研究通过全血流式细胞术检测了50例AML患者诊断时的血小板功能。在体外血小板激动剂刺激后,分析血小板活化标志物,并与20名健康个体进行比较。为检测近期体内血小板活化情况,测定了血浆可溶性P-选择素(sP-选择素)。血小板活化标志物的流式细胞术分析显示,CD62P降低[35.6对118.5 x 10(3)等效可溶性荧光染料分子(MESF);P < 0.0001],CD63降低(11.3对50.7 x 10(3) MESF;P < 0.0001),PAC-1降低(41.5对90.5%;P = 0.0001),而CD42b降低异常(45.6对70%;P < 0.0001)。患者和健康对照的sP-选择素水平相似(0.04对0.27 fg/血小板;P = 0.84)。所呈现的数据表明,AML发病机制可能导致多种血小板缺陷,涉及黏附、聚集和分泌,并证明流式细胞术是血小板减少患者血小板功能分析的可行方法。