Gidaro Antonio, Manetti Roberto, Delitala Alessandro Palmerio, Soloski Mark Johns, Lambertenghi Deliliers Giorgio, Castro Dante, Soldini Davide, Castelli Roberto
Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital, University of Milan, Via G.B. Grassi N° 74, 20157 Milan, Italy.
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Piazza Università N° 21, 07100 Sassari, Italy.
J Clin Med. 2022 May 11;11(10):2720. doi: 10.3390/jcm11102720.
Introduction: Multiple myeloma (MM) is characterized by a high prevalence of thrombotic complications. Microvesicles (MVs) are small membrane vesicles released from activated cells, and they may potentially contribute to thrombosis. Methods: We have evaluated the plasma levels of MVs and cytokines (IL-10, IL-17, and TGF-β in MM and Watch and Wait Smoldering MM (WWSMM) from patients and related them to thrombotic complications. The secondary aim was to assess the impact of ongoing therapy on MV and on cytokine levels. Result: 92 MM and 31 WWSMM were enrolled, and 14 (12%) experienced a thrombotic episode. Using univariate analysis, TGF-β and MV were significantly higher in patients with thrombotic events (p = 0.012; p = 0.008, respectively). Utilizing a Cox proportional hazard model, we confirmed this difference (TGF-β p = 0.003; Odds ratio 0.001, 95% CI 0−0.003 and MV p = 0.001; Odds ratio 0.003, 95% CI 0.001−0.005). Active treatment management displayed higher levels of MV (p < 0.001) and lower levels of glomerular filtration-rate (p < 0.001), IL-17 (p < 0.001) as compared to the WWSMM group. The TGF-β values of immunomodulatory derivatives patients were lower in the WWSMM (p < 0.001) and Dexamethasone/Bortezomib subgroup (p < 0.001). Conclusion: The increased levels of MVs in active regimens add insight into the mechanisms of hypercoagulation in MM. In addition, a role for cytokine-related thrombosis is also suggested.
多发性骨髓瘤(MM)的特征是血栓形成并发症的高发生率。微泡(MVs)是从活化细胞释放的小膜泡,它们可能潜在地导致血栓形成。方法:我们评估了患者MM和观察等待型冒烟型MM(WWSMM)中MVs和细胞因子(IL-10、IL-17和TGF-β)的血浆水平,并将它们与血栓形成并发症相关联。次要目的是评估正在进行的治疗对MVs和细胞因子水平的影响。结果:纳入了92例MM患者和31例WWSMM患者,其中14例(12%)发生了血栓事件。使用单因素分析,血栓形成事件患者的TGF-β和MVs显著更高(分别为p = 0.012;p = 0.008)。利用Cox比例风险模型,我们证实了这种差异(TGF-β p = 0.003;优势比0.001,95%置信区间0 - 0.003;MVs p = 0.001;优势比0.003,95%置信区间0.001 - 0.005)。与WWSMM组相比,积极治疗管理显示出更高水平的MVs(p < 0.001)和更低水平的肾小球滤过率(p < 0.001)、IL-17(p < 0.001)。免疫调节衍生物患者的TGF-β值在WWSMM组(p < 0.001)和地塞米松/硼替佐米亚组(p < 0.001)中较低。结论:积极治疗方案中MVs水平的升高为MM高凝机制提供了新见解。此外,还提示了细胞因子相关血栓形成的作用。