Phosphatidylserine-exposing cells contribute to the hypercoagulable state in patients with multiple myeloma

Guo,Li; Tong,Dongxia; Yu,Muxin; Zhang,Yan; Li,Tao; Wang,Chunxu; Zhou,Peng; Jin,Jiaqi; Li,Baorong; Liu,Yingmiao; Liu,Ruipeng; Novakovic,Valerie A.; Dong,Zengxiang; Tian,Ye; Kou,Junjie; Bi,Yayan; Zhou,Jin; Shi,Jialan

doi:10.3892/ijo.2018.4354

Phosphatidylserine-exposing cells contribute to the hypercoagulable state in patients with multiple myeloma

Authors:
- Li Guo
- Dongxia Tong
- Muxin Yu
- Yan Zhang
- Tao Li
- Chunxu Wang
- Peng Zhou
- Jiaqi Jin
- Baorong Li
- Yingmiao Liu
- Ruipeng Liu
- Valerie A. Novakovic
- Zengxiang Dong
- Ye Tian
- Junjie Kou
- Yayan Bi
- Jin Zhou
- Jialan Shi
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Affiliations: 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, Department of Stomatology, The First Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Cardiology, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Research and Surgery, VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02132, USA, Department of Cardiology, The First Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: April 3, 2018 https://doi.org/10.3892/ijo.2018.4354
Pages: 1981-1990

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Abstract

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.

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