title: Enhanced Procoagulant Activity on Blood Cells after Acute Ischemic Stroke.
abstract: The role of phosphatidylserine (PS)-mediated procoagulant activity (PCA) in stroke remains unclear. To ascertain this role, early dynamic evolution of PS exposure on blood cells and released microparticles (MPs) and the corresponding PCA were evaluated in patients with acute ischemic stroke (AIS). Flow cytometry analyses revealed that initial levels of PS exposure on erythrocyte, platelet, and leukocyte were 2.40-, 1.36-, and 1.38-fold higher, respectively, in AIS than the risk factor-matched (RF) controls. Concomitantly, total PS+MPs were increased in AIS (1949 ± 483/μl) compared with the RF group (1674 ± 387/μl; P = 0.019) and healthy controls (1052 ± 179/μl; P < 0.001). Specifically, PS+erythrocytes gradually increased within 1 week. PS+platelets and MPs peaked at 24 h and declined at 7 days, while PS+leukocytes were markedly elevated at 24 h. Further, PS exposure on blood cells and MPs in stroke resulted in shortened clotting time with an accompanying increase in FXa and thrombin formation significantly. Treatment with lactadherin, a PS antagonist, delayed the coagulation time by approximately 20 % and blocked the generation of FXa and thrombin by about 50 %. Furthermore, initial counts of PS+platelets and platelet MPs significantly correlated with stroke severity. Thrombin generation promoted by platelets and MPs at 12 h was significantly higher in patients with cardioembolism than in patients without. The thrombophilic susceptibility of AIS patients can be partly ascribed to PS exposure on blood cells and the release of MPs. Our studies identify PS exposure as a potentially novel therapeutic target in the treatment of AIS.
authors.affiliation: Department of Hematology, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Cardiology, the First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Lixiu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Hematology, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Neurology, the Fourth Hospital, Harbin Medical University, Harbin, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Chi
authors.affiliation: Department of Hematology, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Hematology, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Tong
authors.affiliation: Department of Hematology, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
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 Hematology, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Deng
authors.affiliation: Department of Research, Brigham and Women's Hospital, Harvard Medical School, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Novakovic
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Hemant S
authors.initials: HS
authors.lastname: Thatte
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 First Hospital, Harbin Medical University, Harbin, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Hematology, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China. jialan_shi@hms.harvard.edu.|Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, VA Boston Healthcare System, Boston, MA, USA. jialan_shi@hms.harvard.edu.
authors.forename: Jialan
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Hematology, the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China. zhoujinyzp@sina.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, the Second Hospital, Harbin Medical University, Harbin, China. koujunjie000@163.com.
authors.forename: Junjie
authors.initials: J
authors.lastname: Kou
authors.affiliation: Department of Neurosurgery, the Second Hospital, Harbin Medical University, Harbin, China. hushaoshan000@163.com.
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Hu
mesh_terms: D000368:Aged; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood*; D055252:Cell-Derived Microparticles / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000097:blood*; D020521:Stroke / Q000097:blood*; D013917:Thrombin / Q000378:metabolism
chemical_list: D001779:Blood Coagulation Factors; D010718:Phosphatidylserines; C045071:leukocyte procoagulant activity; D013917:Thrombin
keywords: Acute ischemic stroke; Microparticles; Phosphatidylserine; Procoagulant; Thrombin