title: Phosphatidylserine exposing-platelets and microparticles promote procoagulant activity in colon cancer patients.
abstract: BACKGROUND
  Colon cancer is invariably accompanied by altered coagulation activity; however, the precise role of phosphatidylserine (PS) in the hypercoagulable state of colon cancer patients remains unclear. We explored the exposure of PS on platelets and microparticles (MPs), and evaluate its role in procoagulant activity in colon cancer patients.
  
  
  METHODS
  PS-positive platelets and MPs, mainly from platelets and endothelial cells, were detected by flow cytometry and confocal microscopy, and their procoagulant activity was assessed with purified coagulation complex assays, clotting time, and fibrin turbidity.
  
  
  RESULTS
  Plasma levels of PS-positive platelets increased gradually from stage I to IV and were higher in all stages of the patients than in the healthy control, while PS-positive platelet-derived MPs only increased significantly in stage III/IV patients. Meanwhile, PS-positive MPs and endothelial-derived MPs in stage II/III/IV patients were markedly higher than ones in controls but no difference with stage I. Tissue factor positive MPs were higher in all 4 stages of colon cancer patients than in the healthy control. Platelets and MPs from the patients demonstrated significantly enhanced intrinsic/extrinsic FXa and thrombin generation, greatly shortened coagulation time, and increased fibrin formation. Combined treatment with PS antagonist lactadherin, strongly prolonged the coagulation time and reduced fibrin formation by inhibiting factor tenase and prothrombinase complex activity. In contrast, pretreatment with anti tissue factor antibody played a lesser role in suppression of procoagulant activity.
  
  
  CONCLUSIONS
  Our results suggest that PS-positive platelets and MPs contribute to hypercoagulability and represent a potential therapeutic target to prevent coagulation in patients with colon cancer.
authors.affiliation: Department of Colorectal Surgery, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, People's Republic of China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, People's Republic of China.
authors.forename: Yayan
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150086, People's Republic of China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Kou
authors.affiliation: Department of Medicine, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, People's Republic of China. jialan_shi@hms.harvard.edu.|Department of Surgery, Brigham and Women's Hospital, VA Boston Healthcare System, Harvard Medical School, Boston, 02132, USA. jialan_shi@hms.harvard.edu.|Department of Hematology, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, People's Republic of China. jialan_shi@hms.harvard.edu.
authors.forename: Jialan
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Colorectal Surgery, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, People's Republic of China. piaodaxun2015@163.com.
authors.forename: Daxun
authors.initials: D
authors.lastname: Piao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D010718:Phosphatidylserines; D013925:Thromboplastin; D013917:Thrombin
keywords: Colon cancer; Phosphatidylserine; Platelets and microparticles; Procoagulant activity