Division of Immunohematology and Transfusion Medicine, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Thromb Res. 2013 Jul;132(1):88-93. doi: 10.1016/j.thromres.2013.05.003. Epub 2013 Jun 2.
Essential Thrombocythemia (ET) and Polycythemia Vera (PV) patients are characterized by an increased rate of thrombotic complications and by several abnormalities of platelets, more pronounced in JAK2V617F positive patients. The aim of this study was to characterize the platelet aggregation as well as the platelet procoagulant potential induced by several different agonists in ET and PV patients.
Venous blood samples were obtained from 65 ET and 51 PV patients. Whole blood impedance aggregometry was utilized to characterize platelet aggregation induced by collagen, ADP, thrombin receptor activating peptide and arachidonic acid, while the Calibrated Automated Thrombogram (CAT) assay was used to determine the thrombin generation (TG) potential induced by ADP in platelet-rich plasma. CAT assay was also performed in the presence of annexin V to evaluate the contribution of platelet phospholipids to TG.
ADP-induced platelet aggregation and TG were significantly increased in ET and PV patients compared to controls. The highest values were observed in JAK2V617F positive patients and in patients on aspirin. In these subjects, annexin V was less effective in inhibiting both basal and ADP-induced TG. This study demonstrates for first time that platelets from ET and PV patients are more responsive to the ADP stimulus, in terms of both increased platelet aggregation, and enhanced TG, particularly in the JAK2V617F positive patients. Our data support the hypothesis that the use of ADP receptor inhibitors, in addition to aspirin, might be considered in the prevention of thrombosis in these conditions, by allowing a more complete inhibition of platelet functions.
特发性血小板增多症(ET)和真性红细胞增多症(PV)患者的血栓并发症发生率较高,血小板存在多种异常,JAK2V617F 阳性患者更为明显。本研究旨在描述 ET 和 PV 患者在几种不同激动剂诱导下的血小板聚集和血小板促凝潜能。
采集 65 名 ET 和 51 名 PV 患者的静脉血样本。采用全血阻抗聚集法检测胶原、ADP、血栓素受体激活肽和花生四烯酸诱导的血小板聚集,采用校准自动血栓图(CAT)测定富含血小板血浆中 ADP 诱导的凝血酶生成(TG)潜能。CAT 测定也在膜联蛋白 V 的存在下进行,以评估血小板磷脂对 TG 的贡献。
与对照组相比,ADP 诱导的血小板聚集和 TG 在 ET 和 PV 患者中显著增加。在 JAK2V617F 阳性患者和服用阿司匹林的患者中观察到最高值。在这些患者中,膜联蛋白 V 在抑制基础和 ADP 诱导的 TG 方面效果较差。本研究首次证明,ET 和 PV 患者的血小板对 ADP 刺激的反应性更高,表现在血小板聚集增加和 TG 增强,尤其是在 JAK2V617F 阳性患者中。我们的数据支持这样一种假设,即除了阿司匹林之外,还可以考虑使用 ADP 受体抑制剂来预防这些情况下的血栓形成,从而更完全地抑制血小板功能。