title: Phosphatidylserine on blood cells and endothelial cells contributes to the hypercoagulable state in cirrhosis.
abstract: The mechanism of thrombogenicity in cirrhosis is largely unknown. Our objective was to study the relationship between phosphatidylserine on blood cells and endothelial cells and the hypercoagulable state in cirrhotic patients.
  
  
  
  Patients with cirrhosis and healthy controls were studied. Lactadherin was used to quantify phosphatidylserine exposure on blood cells and endothelial cells. Procoagulant activity of cells was evaluated using clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. Phosphatidylserine exposure, fibrin strands and FVa/Xa binding on cells were observed using confocal microscopy.
  
  
  
  Our study showed that phosphatidylserine exposure on erythrocytes, platelets and leucocytes in cirrhotic patients increased progressively with Child-Pugh categories. In addition, we found that endothelial cells treated with cirrhotic serum in vitro exposed more phosphatidylserine than those exposed to healthy serum. The exposed phosphatidylserine supported a shorter coagulation time and increased FXa, thrombin and fibrin formation. Notably, phosphatidylserine+erythrocytes also promoted shorter coagulation times and more fibrin generation in cirrhotic microparticle-depleted plasma, regardless of Child-Pugh categories. Confocal microscopy data showed that the FVa/FXa complex and fibrin fibrils colocalized with phosphatidylserine on endothelial cells. Lactadherin significantly inhibited FXa and thrombin generation and consequently decreased fibrin production in normal or cirrhotic plasma.
  
  
  
  These results lead us to believe that exposed phosphatidylserine on activated or injured erythrocytes, platelets, leucocytes and endothelial cells plays an important role in the hypercoagulable state in cirrhotic patients. Thus, blocking phosphatidylserine binding sites might be a new therapeutic target for preventing thrombosis.
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Muhua
authors.initials: M
authors.lastname: Cao
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Cardiology, The Second Hospital, Harbin Medical University, Harbin, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Ding
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Deng
authors.affiliation: Department of Cardiology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Zengxiang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China.
authors.forename: He
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Research, VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Novakovic
authors.affiliation: Department of Cardiology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yayan
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Department of Cardiology, The Second Hospital, Harbin Medical University, Harbin, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Kou
authors.affiliation: Department of Cardiology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Departments of Hematology, The First Hospital, Harbin Medical University, Harbin, China.|Department of Surgery, VA Boston Healthcare System, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jialan
authors.initials: J
authors.lastname: Shi
mesh_terms: D000328:Adult; D001773:Blood Cells / Q000378:metabolism*; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles; D002681:China; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism; D019851:Thrombophilia / Q000209:etiology*
chemical_list: D010718:Phosphatidylserines; D005337:Fibrin; D013917:Thrombin
keywords: blood cells; cirrhosis; endothelial cells; hypercoagulable state; phosphatidylserine