Agouti Imane, Cointe Sylvie, Robert Stéphane, Judicone Coralie, Loundou Anderson, Driss Fathi, Brisson Alain, Steschenko Dominique, Rose Christian, Pondarré Corinne, Bernit Emmanuelle, Badens Catherine, Dignat-George Françoise, Lacroix Romaric, Thuret Isabelle
Centre de Référence Maladies Rares Thalassémies, Marseille-Lyon, Service d'Hémato-Oncologie Pédiatrique, Hôpital de la Timone, APHM, Marseille, France.
VRCM, INSERM UMR-S1076, UFR de Pharmacie, Université Aix Marseille, Marseille, France.
Br J Haematol. 2015 Nov;171(4):615-24. doi: 10.1111/bjh.13609. Epub 2015 Jul 24.
The level of circulating platelet-, erythrocyte-, leucocyte- and endothelial-derived microparticles detected by high-sensitivity flow cytometry was investigated in 37 β-thalassaemia major patients receiving a regular transfusion regimen. The phospholipid procoagulant potential of the circulating microparticles and the microparticle-dependent tissue factor activity were evaluated. A high level of circulating erythrocyte- and platelet-microparticles was found. In contrast, the number of endothelial microparticles was within the normal range. Platelet microparticles were significantly higher in splenectomized than in non-splenectomized patients, independent of platelet count (P < 0·001). Multivariate analysis indicated that phospholipid-dependent procoagulant activity was influenced by both splenectomy (P = 0·001) and platelet microparticle level (P < 0·001). Erythrocyte microparticles were not related to splenectomy, appear to be devoid of proper procoagulant activity and no relationship between their production and haemolysis, dyserythropoiesis or oxidative stress markers could be established. Intra-microparticle labelling with anti-HbF antibodies showed that they originate only partially (median of 28%) from thalassaemic erythropoiesis. In conclusion, when β-thalassaemia major patients are intensively transfused, the procoagulant activity associated with thalassaemic erythrocyte microparticles is probably diluted by transfusions. In contrast, platelet microparticles, being both more elevated and more procoagulant, especially after splenectomy, may contribute to the residual thrombotic risk reported in splenectomized multi-transfused β-thalassaemia major patients.
通过高灵敏度流式细胞术检测了37例接受常规输血方案的重型β地中海贫血患者循环中血小板、红细胞、白细胞和内皮细胞衍生的微粒水平。评估了循环微粒的磷脂促凝潜力和微粒依赖性组织因子活性。发现循环中红细胞和血小板微粒水平较高。相比之下，内皮微粒数量在正常范围内。脾切除患者的血小板微粒明显高于未脾切除患者，与血小板计数无关（P<0.001）。多变量分析表明，磷脂依赖性促凝活性受脾切除术（P=0.001）和血小板微粒水平（P<0.001）的影响。红细胞微粒与脾切除术无关，似乎缺乏适当的促凝活性，且无法确定其产生与溶血、红细胞生成异常或氧化应激标志物之间的关系。用抗HbF抗体进行微粒内标记显示，它们仅部分（中位数为28%）源自地中海贫血红细胞生成。总之，当重型β地中海贫血患者大量输血时，与地中海贫血红细胞微粒相关的促凝活性可能被输血稀释。相比之下，血小板微粒，尤其是在脾切除术后，水平更高且促凝性更强，可能导致脾切除的多次输血重型β地中海贫血患者中报道的残余血栓形成风险。
