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Annals of Hematology

, Volume 97, Issue 4, pp 605–616 | Cite as

Phosphatidylserine-exposing blood and endothelial cells contribute to the hypercoagulable state in essential thrombocythemia patients

  • Dongxia Tong
  • Muxin Yu
  • Li Guo
  • Tao Li
  • Jihe Li
  • Valerie A. Novakovic
  • Zengxiang Dong
  • Ye Tian
  • Junjie Kou
  • Yayan Bi
  • Jinghua Wang
  • Jin ZhouEmail author
  • Jialan ShiEmail author
Original Article

Abstract

The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P < 0.001)] than those in controls. Among ET patients, those with JAK2 mutations showed higher levels of PS-positive erythrocytes, platelets, neutrophils, and serum-cultured ECs than TN patients or those with CALR mutations, which show similar levels. Coagulation function assays showed that higher levels of PS-positive blood cells and serum-cultured ECs led to markedly shortened coagulation time and dramatically increased levels of FXa, thrombin, and fibrin production. This procoagulant activity could be largely blocked by addition of lactadherin (approx. 70% inhibition). Confocal microscopy showed that the FVa/FXa complex and fibrin fibrils colocalized with PS on ET serum-cultured ECs. Additionally, we found a relationship between D-dimer, prothrombin fragment F1 + 2, and PS exposure. Our study reveals a previously unrecognized link between hypercoagulability and exposed PS on cells, which might also be associated with distinct thrombotic risks among mutational subtypes in ET. Thus, blocking PS-binding sites may represent a new therapeutic target for preventing thrombosis in ET.

Keywords

Essential thrombocythemia Mutational subtypes Thrombosis Phosphatidylserine Cells 

Notes

Acknowledgements

We thank Yanming Xue for the sample collection and Lu Zhao for the excellent technical assistance.

Funding information

This work was supported by grants from the National Science Foundation of China (81470301, 81670128).

Compliance with ethical standards

This study was approved by the Ethics Committee of Harbin Medical University according to the Helsinki Declaration and informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2018_3228_MOESM1_ESM.doc (62 kb)
ESM 1 (DOC 61 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Hematology, First HospitalHarbin Medical UniversityHarbinChina
  2. 2.Department of Cardiology, First HospitalHarbin Medical UniversityHarbinChina
  3. 3.Department of Research, VA Boston Healthcare System, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  4. 4.Department of Cardiology, Second HospitalHarbin Medical UniversityHarbinChina
  5. 5.Department of Hematology, Second HospitalHarbin Medical UniversityHarbinChina
  6. 6.Department of Surgery, VA Boston Healthcare System, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

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