Department of Hematology, The First Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Department of Neurosurgery, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Int J Oncol. 2018 Jun;52(6):1981-1990. doi: 10.3892/ijo.2018.4354. Epub 2018 Apr 3.
Multiple myeloma (MM) is characterized by an increased incidence of thromboembolic events, particularly when treated with immunomodulatory drugs (IMiDs) in combination with dexamethasone. The optimal prophylactic strategy to prevent the hypercoagulable state of patients with MM is still debated. The aim of the current study was to investigate the definitive role of phosphatidylserine (PS) in supporting procoagulant activity (PCA) in patients with MM. Patients with MM (n=20) and healthy subjects (n=15) were recruited for the present study. PS analyses were performed by flow cytometry and confocal microscopy. The PCA was evaluated by clotting time, purified coagulation complex assays and fibrin production assays. The percentage of PS+ blood cells was significantly higher in patients with MM than in healthy subjects. Additionally, the patient serum induced more PS exposure on endothelial cells (ECs) in vitro than serum from healthy subjects. Isolated blood cells from patients with MM and ECs cultured with patient serum in vitro demonstrated significantly shortened coagulation time, greatly intrinsic/extrinsic factor Xa generation and increased thrombin formation. In addition, the levels of PS+ erythrocytes, platelets, leukocytes, and ECs incubated with IMiDs and dexamethasone were higher than with IMiDs alone. The findings support the hypothesis that increased PS exposure on blood cells and ECs participates in the hypercoagulable state in patients with MM. Thus, blocking PS may be a novel therapeutic target for the prevention of thrombosis in these patients.
多发性骨髓瘤（MM）的特点是血栓栓塞事件的发生率增加，特别是在与地塞米松联合使用免疫调节药物（IMiDs）治疗时。预防 MM 患者高凝状态的最佳预防策略仍存在争议。本研究旨在探讨磷脂酰丝氨酸（PS）在支持 MM 患者促凝活性（PCA）中的明确作用。本研究招募了 20 名 MM 患者和 15 名健康受试者。通过流式细胞术和共聚焦显微镜进行 PS 分析。通过凝血时间、纯化凝血复合物测定和纤维蛋白生成测定评估 PCA。与健康受试者相比，MM 患者的 PS+血细胞百分比明显更高。此外，患者血清在体外诱导内皮细胞（ECs）上 PS 暴露的程度高于健康受试者的血清。从 MM 患者分离的血液细胞和在体外用患者血清培养的 ECs 表现出明显缩短的凝血时间、大大增加的内在/外在因子 Xa 生成和增加的凝血酶形成。此外，与仅使用 IMiDs 相比，孵育有 IMiDs 和地塞米松的 PS+红细胞、血小板、白细胞和 ECs 的水平更高。这些发现支持这样一种假设，即血细胞和 ECs 上 PS 暴露的增加参与了 MM 患者的高凝状态。因此，阻断 PS 可能是预防这些患者血栓形成的新的治疗靶点。
