Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria; Department of Internal Medicine, Cardiology and Nephrology, Landesklinikum Wiener Neustadt, Wiener Neustadt, Austria.
Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Transl Res. 2018 Oct;200:35-42. doi: 10.1016/j.trsl.2018.05.009. Epub 2018 Jun 13.
Patients with myeloproliferative neoplasms (MPN) are at an increased risk of thrombotic events even during antiplatelet therapy with aspirin. In the current study, we sought to investigate the association of the platelet count with the inhibitory potential of antiplatelet therapy in MPN. We determined arachidonic acid (AA)- and adenosine diphosphate (ADP)-inducible platelet reactivity by multiple electrode aggregometry in 93 patients with essential thrombocythemia, polycythemia vera or primary myelofibrosis. In patients without aspirin therapy (n = 44), the platelet count did not correlate with platelet aggregation. In aspirin-treated patients (n = 49), we observed a moderate correlation of residual AA-inducible platelet aggregation with the platelet count (r = 0.49; P < 0.001). Further, patients with high on-treatment residual platelet reactivity to AA (HRPR AA) had a significantly higher platelet count than patients without HRPR AA (547 × 10/L [340 - 644 × 10/L] vs 358 × 10/L [242 - 501 × 10/L], P = 0.01). Receiver-operating characteristic curve analysis revealed a platelet count of ≥317 × 10/L as best threshold to distinguish between patients without and with HRPR AA (area under the curve: 0.73). After adding the direct ADP P2Y inhibitor cangrelor to blood samples from all 93 patients in vitro, residual ADP-inducible platelet reactivity correlated weakly with the platelet count (r = 0.26, P = 0.01), but the platelet count did not differ significantly between patients with and without HRPR ADP (396 × 10/L [316 - 644 × 10/L] vs 340 × 10/L [241 - 489 × 10/L]; P = 0.2). In conclusion, our findings suggest that the extent of platelet inhibition by aspirin in patients with MPN at least in part depends on their individual platelet count.
骨髓增殖性肿瘤（MPN）患者即使接受阿司匹林抗血小板治疗，也存在血栓形成事件的风险增加。在本研究中，我们旨在研究血小板计数与 MPN 患者抗血小板治疗抑制潜力之间的相关性。我们通过多电极聚集仪测定了 93 例原发性血小板增多症、真性红细胞增多症或原发性骨髓纤维化患者的花生四烯酸（AA）和二磷酸腺苷（ADP）诱导的血小板反应性。在未接受阿司匹林治疗的患者（n=44）中，血小板计数与血小板聚集无关。在接受阿司匹林治疗的患者（n=49）中，我们观察到 AA 诱导的残余血小板聚集与血小板计数呈中度相关（r=0.49；P<0.001）。此外，AA 高治疗后残余血小板反应性（HRPR AA）的患者的血小板计数显著高于无 HRPR AA 的患者（547×10/L[340-644×10/L] vs 358×10/L[242-501×10/L]，P=0.01）。受试者工作特征曲线分析显示，血小板计数≥317×10/L 可作为区分无 HRPR AA 和有 HRPR AA 患者的最佳阈值（曲线下面积：0.73）。在用体外所有 93 例患者的血液样本加入直接 ADP P2Y 抑制剂坎格雷洛后，残余 ADP 诱导的血小板反应性与血小板计数弱相关（r=0.26，P=0.01），但有 HRPR ADP 和无 HRPR ADP 的患者的血小板计数无显著差异（396×10/L[316-644×10/L] vs 340×10/L[241-489×10/L]；P=0.2）。总之，我们的研究结果表明，MPN 患者的阿司匹林抗血小板治疗抑制程度至少部分取决于其个体血小板计数。
