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Thromb Haemost 2012; 107(04): 681-689
DOI: 10.1160/TH11-09-0673
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Procoagulant activity of erythrocytes and platelets through phosphatidylserine exposure and microparticles release in patients with nephrotic syndrome

Chunyan Gao
1   Health Ministry Key Laboratory of Cell Transplantation, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Hospital, Harbin Medical University, Harbin, China
,
Rui Xie
1   Health Ministry Key Laboratory of Cell Transplantation, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Hospital, Harbin Medical University, Harbin, China
,
Chengyuan Yu
2   Department of Nephrology, The First Hospital, Harbin Medical University, Harbin, China
,
Qin Wang
2   Department of Nephrology, The First Hospital, Harbin Medical University, Harbin, China
,
Fangfang Shi
2   Department of Nephrology, The First Hospital, Harbin Medical University, Harbin, China
,
Chunying Yao
2   Department of Nephrology, The First Hospital, Harbin Medical University, Harbin, China
,
Rujuan Xie
2   Department of Nephrology, The First Hospital, Harbin Medical University, Harbin, China
,
Jin Zhou
1   Health Ministry Key Laboratory of Cell Transplantation, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Hospital, Harbin Medical University, Harbin, China
,
Gary E. Gilbert
3   Medicine Departments of VA Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts, USA
,
Jialan Shi
1   Health Ministry Key Laboratory of Cell Transplantation, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Hospital, Harbin Medical University, Harbin, China
3   Medicine Departments of VA Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts, USA
› Author Affiliations
Further Information

Publication History

Received: 26 September 2011

Accepted after major revision: 09 January 2012

Publication Date:
29 November 2017 (online)

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Summary

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.

Keywords

Phosphatidylserine - microparticles - nephrotic syndrome - lactadherin
 

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