CHU Brest, Laboratoire d'Hématologie, Hôpital La Cavale Blanche, INSERM, U613, Université de Brest, UFR Médecine et Sciences de la Santé, Brest, France.
Thromb Res. 2010 Sep;126(3):238-42. doi: 10.1016/j.thromres.2010.06.025. Epub 2010 Jul 24.
Microparticles (MPs) are membrane fragments ranging in size from 0.1 to 1 microm, and are considered as biomarkers reflecting prothrombotic state in many clinical diseases. The clinical course of myeloproliferative neoplasms (MPN) being frequently complicated by thrombotic events, we determined the MPs activity, i.e. circulating procoagulant activity (CPA), in polycythemia vera (PV) and essential thrombocythemia (ET) patients. To evaluate the influence of MPs on the coagulation, a thrombin generation test was realized in the absence and presence of thrombomodulin (TM). Compared with controls, patients had a higher CPA (24.0+/-9.0 vs 10.6+/-4.4 nM, p<0.001), which was associated with a lower inhibition of the thrombin generation in the presence of TM (20.1+/-9.5% vs 28.4+/-11.8%, p<0.001), compatible with a low sensitivity to TM. This sensitivity was influenced by the JAK2V617F mutational status, homozygous patients presenting the lowest inhibition rate of the thrombin generation. Filtration through a 0.22 microm membrane increased the sensitivity to TM in plasma, suggesting an influence of MPs in the "TM-resistance" observed in patients. Moreover, MPN patients receiving antiplatelet and/or cytoreductive therapies, our study suggests that CPA might be influenced by cytoreductive therapy. In conclusion, our data evidence in MPN patients the occurrence of an acquired "TM-resistance" partly determined by circulating microparticles. This TM-resistance might contribute to the hypercoagulable state observed in MPN patients, but the predictive value of the "TM-resistance" for thrombosis had not been evaluated.
微粒（MPs）是大小在 0.1 到 1 微米之间的膜碎片，被认为是许多临床疾病中反映促血栓状态的生物标志物。骨髓增生性肿瘤（MPN）的临床病程常伴有血栓事件，我们测定了真性红细胞增多症（PV）和原发性血小板增多症（ET）患者的 MPs 活性，即循环促凝活性（CPA）。为了评估 MPs 对凝血的影响，在缺乏和存在血栓调节蛋白（TM）的情况下进行了凝血酶生成试验。与对照组相比，患者的 CPA 更高（24.0+/-9.0 对 10.6+/-4.4 nM，p<0.001），这与 TM 存在时凝血酶生成的抑制作用降低有关（20.1+/-9.5%对 28.4+/-11.8%，p<0.001），与 TM 的低敏感性一致。这种敏感性受 JAK2V617F 突变状态的影响，纯合子患者的凝血酶生成抑制率最低。通过 0.22 微米膜过滤增加了 TM 在血浆中的敏感性，表明 MPs 对患者中观察到的“TM 抵抗”有影响。此外，接受抗血小板和/或细胞减少治疗的 MPN 患者，我们的研究表明，CPA 可能受到细胞减少治疗的影响。总之，我们的数据在 MPN 患者中证实了获得性“TM 抵抗”的发生，这种 TM 抵抗部分由循环 MPs 决定。这种 TM 抵抗可能导致 MPN 患者的高凝状态，但“TM 抵抗”对血栓形成的预测价值尚未得到评估。
