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Thromb Haemost 2013; 109(06): 1025-1032
DOI: 10.1160/TH12-11-0811
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Role of erythrocytes and platelets in the hypercoagulable status in polycythemia vera through phosphatidylserine exposure and microparticle generation

Xiaoyan Tan
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Jialan Shi
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
2   Medicine Departments of VA Boston Healthcare System, Brigham and Women′s Hospital, and Harvard Medical School, Boston, Massachussetts, USA
,
Yueyue Fu
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Chunyan Gao
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Xue Yang
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Jianan Li
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Wei Wang
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Jinxiao Hou
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Huibo Li
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
,
Jin Zhou
1   Heilongjiang Key Laboratory of Blood and Hematopoietic System Diseases, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin, China
› Author Affiliations Financial support: This work was supported by the National Natural Science Foundation of China (81270589, 81270588), the Heilongjiang Public Technology Service Platform Foundation of Stem Cells and Biological Treatment (PG09J003), and the Health Department Foundation of Heilongjiang Province (2009–548, 2009–549).
Further Information

Publication History

Received: 09 November 2012

Accepted after major revision: 24 February 2013

Publication Date:
22 November 2017 (online)

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Summary

The development of thrombosis in polycythaemia vera (PV) involves multifactorial processes including pathological activation of blood cells. Release of microparticles (MPs) by activated cells in diseases is associated with thrombotic risk, but relatively few data are available in PV. The aim of the present study was to investigate the increase in MP release and exposure of phosphatidylserine (PS) on the outer membrane of MP-origin cells in patients with PV, and to analyse their procoagulant activity (PCA). PS-positive MPs and cells were detected by flow cytometry, while PCA was assessed with clotting time and purified coagulation complex assays. We found that PV patients had elevated circulating lactadherin+ MPs, which mostly originating from erythrocytes, platelets, granulocytes, and endothelial cells, as well as increased PS exposing erythrocytes/platelets as compared to secondary polycythaemia patients or healthy controls. These PS-bearing MPs and cells were highly procoagulant. Moreover, lactadherin competed factor V and VIII to PS and inhibited about 90% of the detected PCA in a dose-response manner while anti-TF antibody did no significant inhibition. Treatment with hydroxyurea is associated with a decrease in PS exposure and lactadherin+ MP release of erythrocytes/platelets. Our data demonstrate that PV patients are characterised by increased circulating procoagulant MPs and PS exposing erythrocytes/platelets, which could contribute to the hypercoagulable state in these patients.

Keywords

Phosphatidylserine - microparticles - polycythaemia vera - lactadherin
 

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