Li Panpan, Xu Bei, Xu Jiadai, Xu Yanyan, Wang Yawen, Chen Chen, Liu Peng
Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Int J Mol Sci. 2023 Sep 14;24(18):14097. doi: 10.3390/ijms241814097.
Lenalidomide, a well-established drug for the treatment of multiple myeloma, significantly enhances patients' survival. Previous clinical studies have demonstrated that its main side effect is an increased risk of thrombotic events. However, the underlying mechanism remains unexplored. Therefore, this study aims to elucidate the mechanism and offer insights into the selection of clinical thrombotic prophylaxis drugs. Firstly, we conducted a retrospective analysis of clinical data from 169 newly diagnosed multiple myeloma patients who received lenalidomide. To confirm the impact of lenalidomide on thrombosis formation, FeCl-induced thrombosis and deep venous thrombosis models in mice were established. To investigate the effects of lenalidomide on platelet function, both in vivo and in vitro experiments were designed. During the follow-up period, 8 patients developed thrombotic events, including 8 venous and 1 arterial. Further investigation using mice models demonstrated that lenalidomide significantly promoted the formation of venous thrombosis, consistent with clinical findings. To elucidate the underlying mechanism, assays were conducted to assess platelet function and coagulation. We observed that lenalidomide did not have any noticeable impact on platelet function, both in vitro and in vivo, while administration of lenalidomide resulted in significant decreases in prothrombin time, thrombin time, and prothrombin time ratio in patients, as well as a remarkable reduction in tail-bleeding time in mice. The administration of lenalidomide had no significant impact on platelet function, which may affect venous thrombus formation by affecting coagulation. Therefore, anticoagulant drugs may be superior to antiplatelet drugs in the selection of clinical thrombus prophylaxis.
来那度胺是一种成熟的用于治疗多发性骨髓瘤的药物，能显著提高患者生存率。先前的临床研究表明，其主要副作用是血栓形成事件的风险增加。然而，其潜在机制仍未得到探索。因此，本研究旨在阐明该机制，并为临床血栓预防药物的选择提供见解。首先，我们对169例接受来那度胺治疗的新诊断多发性骨髓瘤患者的临床资料进行了回顾性分析。为了证实来那度胺对血栓形成的影响，我们建立了FeCl诱导的小鼠血栓形成和深静脉血栓形成模型。为了研究来那度胺对血小板功能的影响，我们设计了体内和体外实验。在随访期间，8例患者发生了血栓形成事件，包括8例静脉血栓和1例动脉血栓。使用小鼠模型的进一步研究表明，来那度胺显著促进了静脉血栓的形成，这与临床发现一致。为了阐明潜在机制，我们进行了评估血小板功能和凝血的试验。我们观察到来那度胺在体外和体内对血小板功能均无明显影响，而来那度胺给药导致患者的凝血酶原时间、凝血酶时间和凝血酶原时间比值显著降低，同时小鼠的尾部出血时间也显著缩短。来那度胺给药对血小板功能无显著影响，可能通过影响凝血来影响静脉血栓形成。因此，在临床血栓预防的选择中，抗凝药物可能优于抗血小板药物。
