title: Contributions of phosphatidylserine-positive platelets and leukocytes and microparticles to hypercoagulable state in gastric cancer patients.
abstract: Hypercoagulability in gastric cancer is a common complication and a major contributor to poor prognosis. This study aimed to determine procoagulant activity of blood cells and microparticles (MPs) in gastric cancer patients. Phosphatidylserine-positive blood cells and MPs, and their procoagulant properties in particular, were assessed in 48 gastric cancer patients and 35 healthy controls. Phosphatidylserine-positive platelets, leukocytes, and MPs in patients with tumor-node-metastasis stage III/IV gastric cancer were significantly higher than those in stage I/II patients or healthy controls. Moreover, procoagulant activity of platelets, leukocytes, and MPs in stage III/IV patients was significantly increased compared to the controls, as indicated by shorter clotting time, higher intrinsic and extrinsic factor tenase, and prothrombinase complex activity. Interestingly, lactadherin, which competes with factors V and VIII to bind phosphatidylserine, dramatically prolonged clotting time of the cells and MPs by inhibiting factor tenase and prothrombinase complex activity. Although anti-tissue factor antibody significantly attenuated extrinsic tenase complex activity of leukocytes and MPs, it only slightly prolonged clotting times. Meanwhile, treatment with radical resection reduced phosphatidylserine-positive platelets, leukocytes, and MPs, and prolonged the clotting times of the remaining cells and MPs. Our results suggest that phosphatidylserine-positive platelets, leukocytes, and MPs contribute to hypercoagulability and represent a potential therapeutic target to prevent coagulation in patients with stage III/IV gastric cancer.
authors.affiliation: Department of Gastrointestinal Surgery, The Second Hospital of Harbin Medical University, 246 Xuefu Street, Nangang District, Harbin, 150001, China.
authors.forename: Chunfa
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Medicine, The First Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ruishuang
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Gastrointestinal Surgery, The First Hospital of Harbin Medical University, Harbin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Medicine, The First Hospital of Harbin Medical University, Harbin, China.
authors.forename: Muhua
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Gastrointestinal Surgery, The First Hospital of Harbin Medical University, Harbin, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Medicine, The First Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yayan
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Department of Cardiology, The Second Hospital of Harbin Medical University, Harbin, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Kou
authors.affiliation: Department of Medicine, The First Hospital of Harbin Medical University, Harbin, China. jialan_shi@hms.harvard.edu.|Department of Hematology, The First Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China. jialan_shi@hms.harvard.edu.
authors.forename: Jialan
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Gastrointestinal Surgery, The Second Hospital of Harbin Medical University, 246 Xuefu Street, Nangang District, Harbin, 150001, China. zou4930@163.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zou
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism*; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000097:blood* / Q000150:complications; D019851:Thrombophilia / Q000209:etiology*
chemical_list: D010718:Phosphatidylserines
keywords: Gastric cancer; Microparticles; Phosphatidylserine; Prothrombotic state; Tissue factor