title: Procoagulant activity of erythrocytes and platelets through phosphatidylserine exposure and microparticles release in patients with nephrotic syndrome.
abstract: Recent studies showed that an imbalance of prothrombotic and antithrombotic factors and impaired thrombolytic activity contribute to the thrombophilia of the nephrotic syndrome (NS). However, it is not clear whether blood cell injury and/or activation is involved in hypercoagulability in NS patients. Our objectives were to study the increase in microparticle (MP) release and phosphatidylserine (PS) exposure on the outer membrane of MP-origin cells in NS patients, and to evaluate their procoagulant activity (PCA). The subjects were patients with membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS) and healthy controls. Analyses of MPs and PS exposure were performed using a flow cytometer. PCA was determined by clotting time and purified coagulation complex assays. We found that lactadherin+ MPs, which derived from red blood cells (RBC), platelet and endothelial cell, increased in NS patients. Moreover, PS exposure on RBCs and platelets in each NS group, especially in MN, are higher than that in controls. MP shedding and PS exposure of RBCs/platelets were highly procoagulant in NS patients. However, blockade of PS with lactadherin inhibited over 90% of PCA while an anti-tissue factor antibody had no significant inhibition effect. Our results demonstrate that the thrombophilic susceptibility of NS may be partly ascribed to MP release and PS exposure of RBCs, platelets and endothelial cells. Lactadherin is a sensitive probe for PS that has high anticoagulant activity.
authors.affiliation: 1Health Ministry Key Laboratory of Cell Transplantation, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Hospital, Harbin Medical University,Harbin, China.
authors.forename: C
authors.initials: C
authors.lastname: Gao
authors.forename: R
authors.initials: R
authors.lastname: Xie
authors.forename: C
authors.initials: C
authors.lastname: Yu
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Shi
authors.forename: C
authors.initials: C
authors.lastname: Yao
authors.forename: R
authors.initials: R
authors.lastname: Xie
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: G E
authors.initials: GE
authors.lastname: Gilbert
authors.forename: J
authors.initials: J
authors.lastname: Shi
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D002352:Carrier Proteins; D016022:Case-Control Studies; D003029:Coagulants / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D015951:Factor Xa / Q000096:biosynthesis; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D008894:Milk Proteins / Q000378:metabolism; D009402:Nephrosis, Lipoid / Q000097:blood* / Q000378:metabolism; D010316:Particle Size; D010718:Phosphatidylserines / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D002352:Carrier Proteins; D003029:Coagulants; D036341:Intercellular Signaling Peptides and Proteins; C098942:MFGE8 protein, human; D008894:Milk Proteins; C112214:P47 sperm protein, Sus scrofa; D010718:Phosphatidylserines; D013925:Thromboplastin; D015951:Factor Xa