Multiple myeloma and its treatment contribute to increased platelet reactivity.
Multiple myeloma and its treatment contribute to increased platelet reactivity.
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多发性骨髓瘤及其治疗有助于增加血小板反应性。
DOI：
10.1080/09537104.2023.2264940
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发表时间：
2023
期刊：
影响因子：
3.3
通讯作者：
Mitchell JL
中科院分区：
文献类型：
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作者：
Mitchell JL
多发性骨髓瘤（MM）及其前体状态、郁积性骨髓瘤（SM）和意义不明的单克隆丙种球蛋白病（MGUS）与血栓形成发生率增加相关，但其原因尚不清楚。来那度胺治疗MM可显著改善患者生存率，但通过未知机制显著增加血栓形成风险。该初步研究旨在确定MM及其来那度胺治疗对血小板功能的影响。与健康对照相比，我们分析了MGUS、SM和MM患者的血小板功能。我们报告了MGUS、SM和MM中血小板反应性的增加，其中观察到纤维蛋白原结合、P-选择素暴露、受体表达改变、聚集水平升高和对激动剂刺激的敏感性增强。我们还证明了与治疗前相比，来那度胺治疗后患者血小板反应性增加。我们发现来那度胺治疗血小板性体内反应性增加，这与动脉剪切率下而不是静脉剪切率下较大血栓的形成有关。本研究表明，MGUS、SM和MM患者的血小板反应性和促血栓形成潜力明显增加，在来那度胺治疗后进一步升高。我们的观察结果表明，更详细的研究是必要的，以确定血栓并发症的机制，使新的预防策略，专门针对血小板的发展。
Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of plateletsex vivoincreased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.